Elevated Blood Lactate Research Articles

Lactic acid suppresses LPS-induced mast cell cytokine production by limiting glycolysis and ATP availability

Abstract Sepsis, a life threatening response to infection, has a well-studied initial cytokine storm, with a less understood secondary immunosuppressive phase. Elevated blood lactate and slow lactate clearance are associated with mortality, however, any regulatory role is unknown. We hypothesized that lactic acid contributes to the late phase of sepsis and is not solely a consequence of bacterial infection. Thus far, no studies have examined the effect of lactic acid on sepsis models in vivo or a mechanism by which they suppress LPS activation in vitro. Because mast cells can be activated systemically and contribute to sepsis, we examined lactic acid effects on the mast cell response to the bacterial product LPS. Lactic acid significantly suppressed LPS-induced cytokine production and NFκB-mediated transcription in mouse bone marrow derived mast cells and cytokine production in peritoneal mast cells. Suppressive effects were MCT-1-dependent and observed with sodium lactate or formic acid. Further, lactic acid significantly suppressed cytokine induction following LPS-induced endotoxemia in mice. Because glycolysis is linked to inflammation and lactic acid is a by-product of this process, we examined changes in glucose metabolism. Lactic acid treatment reduced glucose uptake and lactate export during LPS stimulation. Lactic acid effects were mimicked by glycolytic inhibitors and reversed by increasing ATP availability. These results indicate that glycolytic suppression and ATP production are necessary and sufficient for lactic acid effects. Our work suggests that enhancing glycolysis and ATP production could improve immune function, counteracting lactic acid suppressive effects in the immunosuppressive phase of sepsis.

EVALUATION OF SERIAL BLOOD LACTATE AND THE USE OF A POINT-OF-CARE LACTATE METER IN LIVE-STRANDED PINNIPEDS.

Live-stranded pinnipeds often present to rehabilitation centers systemically debilitated with dehydration and poor perfusion. In many terrestrial mammals, blood lactate elevation has been correlated with global tissue hypoxia and decreased circulating blood volume. Serial blood lactate measurements in companion animals and humans have been used to guide fluid resuscitation therapy and evaluate prognosis. The primary objective of this study was to evaluate the prognostic value of serial blood lactate levels in live-stranded pinnipeds in a rehabilitation setting. The secondary objectives were to evaluate the use of a point-of-care lactate meter, and potassium oxalate-sodium fluoride (gray-top) tubes for storing samples for lactate analysis in pinniped patients. Fifty-five live-stranded pinnipeds (30 northern elephant seals [Mirounga angustirostris], 21 Pacific harbor seals [Phoca vitulina richardsi], and four California sea lions [Zalophus californianus]) that presented to a rehabilitation center were manually restrained for blood collection and lactate measurement using a point-of-care analyzer (Lactate Plus™) prior to fluid or other medical therapy. Lactate measurements were repeated 72 hr post admission and prior to euthanasia or release. Plasma samples from gray-top tubes were frozen for 30-100 days at -80°C, then thawed and evaluated using both the LactatePlus and bench-top (ABL 815) analyzers. The point-of-care analyzer was successful in measuring lactate in pinnipeds. Gray-top tubes were effective at preserving lactate levels in frozen plasma samples for up to 100 days. Released animals had significantly greater lactate clearance at 72 hr (P = 0.039) than animals that died or were euthanized. Therefore, lactate clearance, determined by serial blood lactate measurements, may be useful for evaluating prognosis in live-stranded pinnipeds. Initial lactate and lactate values prior to euthanasia or release were not significantly associated with outcome. Given these findings, clinicians should interpret isolated lactate values in pinnipeds with caution.

Acute behavioural and physiological responses of sheep to S/C ivermectin injection

Acute behavioural and physiological responses of sheep to S/C ivermectin injection

Prognostic values of the Berlin definition criteria, blood lactate level, and fibroproliferative changes on high-resolution computed tomography in ARDS patients

BackgroundIn the Berlin definition, acute respiratory distress syndrome (ARDS) is stratified into three stages according to oxygenation severity at the onset. The relevance between ARDS severity and prognosis varies among published reports and has not been verified, especially in Asian patients.MethodsIn this study, we examined the associations between the Berlin definition criteria and prognosis and clinical parameters, including high-resolution computed tomography (HRCT) scores of fibroproliferative changes of the lungs. One hundred fifty-three patients (45 females; mean age, 67 y/o), who met the Berlin definition and received treatment in our intensive care unit between January 2012 and December 2015, were enrolled.ResultsThe severity of ARDS was mild in 42 patients, moderate in 71, and severe in 40. The underlying diseases included pneumonia in 56 patients and aspiration in 43. Forty-two (27.5%) patients were deceased within 30 days, and the 30-day mortality was 10% in mild ARDS, 23% in moderate, and 55% in severe, which were significantly different (P < 0.05). In the non-survivors, APACHE II, SOFA, and SAPS II scores were higher than in the survivors (P < 0.001). Multivariate analyses revealed that elevated blood lactate level (≥ 2.0 mmol/L) and increased HRCT scores were significantly associated with weaning failure and 30-day mortality of the patients with ARDS.ConclusionsThese results suggested that the severity criteria in the Berlin definition might be associated with the prognosis of the patients. Blood lactate levels and HRCT score might be predictive of the outcome of patients with ARDS.

‘Ammonia, lactate and blood gases – A user's guide’

Abstract Basic biochemical tests are frequently obtained in acutely unwell neonates and children, as well as in some elective situations. Correct interpretation can be invaluable in identifying rare inherited primary metabolic disorders, but secondary causes of hyperammonaemia, elevated blood lactate or blood gas derangement are more common and require appropriate treatment of the underlying cause. This Personal Practice guide provides an overview of these tests and their interpretation.

Blood lactate elevation during the lactate stress test supports systemic mitochondrial dysfunction in schizophrenia

There are a wide variety of cadastral objects, ranging from simple 2D entities such as a land parcel, to complex 3D objects such as multistory/multi-owned buildings. The complex infrastructures development happening above and below the ground complicates the processes required for defining rights, restrictions and responsibilities in 3D (3D RRRs). Even in the current, predominantly, 3D analogue cadastral system which relies on 2D drawings and representations, defining 3D RRRs is still a complicated task. With the widespread use of 3D geospatial information technologies, it is increasingly becoming easy to realise and interpret a 3D digital cadastre system. As part of the process of transition from the 2D representation of cadastre towards a 3D digital cadastre, not only will 2D representations be replaced with 3D models, but the examination workflow and its principles also need to be able to manage 3D models. Developing principles and validation rules is a critical requirement to guarantee that the diverse cadastral data is trustable and contains enough detail to define the spatial and legal extents of ownership. This paper proposes a structured framework to define validation rules for 3D cadastral models. The paper’s methodology utilises a case study approach where a plan examination process in Victoria, Australia has been analysed to investigate the principles of examining cadastral plans, and further expanded on for validating 3D digital plans. The paper concludes with a discussion on the implications of the proposed 3D validation rules and proposes future research within the topic of 3D cadastral data validation.

758: Marked variability-cause for concern?

Continuous electronic fetal monitoring (EFM) is widely used to assess intrapartum fetal well-being during labor. However, little guidance is available regarding the frequency and interpretation of marked variability. We investigated the incidence of marked variability before delivery and its association with neonatal morbidity. This is a secondary analysis of a prospective cohort of 8,580 singleton deliveries from 2010-2015 at 37 weeks or beyond. EFM patterns during the 120 minutes prior to delivery were interpreted in 10-minute epochs. The primary outcomes were 1) a composite neonatal morbidity (death, respiratory distress, mechanical ventilation, suspected sepsis, meconium aspiration syndrome, therapeutic hypothermia, hypoxic-ischemic encephalopathy, & seizure) and 2) a composite adverse acid-base status (umbilical artery acidemia pH<7.10, elevated lactate ≥4 mmol/L, elevated base excess < -12). Outcomes were compared between women with and without marked variability defined as fluctuations in EFM amplitude of greater than 25 beats per minute ever in last 120 minutes. Adjusted risk ratios were estimated using multivariable logistic regression. Of the 8,580 women, 390 (4.5%) had marked variability before delivery. 757 (8.8%) of neonates had composite neonatal morbidity and 2,212 (26%) had composite adverse acid-base status. After adjusting for maternal age & obesity, women who had marked variability did not have increased risk of the composite neonatal morbidity 11% vs 8.7% aRR, [95% CI] 1.22 [0.91 1.63], though there was an increase in the risk of respiratory distress 7.2% vs 3.7% 1.85 [1.25, 2.70]. In contrast, there was an increased risk of composite adverse acid-base status 41.5% vs 25% 1.66 [1.47, 1.88]. This finding was driven by an increased risk of elevated lactate 42% vs 25% 1.66 [1.47, 1.88]. Marked variability occurred rarely before delivery and was not associated with increased risk of composite neonatal morbidity. However, marked variability was significantly associated with an increased risk of respiratory distress and elevated cord blood lactate.

The effects of endurance exercise in hypoxia on acid-base balance and potassium kinetics: a randomized crossover design in male endurance athletes

BackgroundExercise-induced disturbance of acid-base balance and accumulation of extracellular potassium (K+) are suggested to elicit fatigue. Exercise under hypoxic conditions may augment exercise-induced alterations of these two factors compared with exercise under normoxia. In the present study, we investigated acid-base balance and potassium kinetics in response to exercise under moderate hypoxic conditions in endurance athletes.MethodsNine trained middle-to-long distance athletes [maximal oxygen uptake (VO2max) 57.2 ± 1.0 mL/kg/min] completed two different trials on different days, consisting of exercise in moderate hypoxia [fraction of inspired oxygen (FiO2) = 14.5%, H trial] and exercise in normoxia (FiO2 = 20.9%, N trial). They performed interval endurance exercise (8 × 4 min pedaling at 80% of VO2max alternated with 2-min intervals of active rest at 40% of VO2max) under hypoxic or normoxic conditions. Venous blood samples were obtained to determine blood lactate, pH, bicarbonate ion, and K+ concentrations before exercise, during exercise, and after exercise.ResultsThe blood lactate concentrations increased significantly with exercise in both trials. Exercise-induced blood lactate elevations were significantly greater in the N trial than in the H trial at all time points (P = 0.012). Bicarbonate ion concentrations (P = 0.001) and blood pH (P = 0.019) during exercise and post-exercise periods were significantly lower in the N trial than in the H trial. A significantly greater exercise-induced elevation in blood K+ concentration was produced in the N trial than in the H trial during exercise and immediately after exercise (P = 0.03).ConclusionsHigh-intensity interval exercise on a cycle ergometer under moderate hypoxic conditions did not elicit a decrease in blood pH or elevation in K+ levels compared with an equivalent level of exercise under normoxic conditions.

Changes of Brain Proton Magnetic Resonance Spectroscopy Study in Hemorrhagic Shock: An Experimental Study on a Rabbit Model

To investigate the changes of cerebral metabolism in rabbit model of hemorrhagic shock by using proton magnetic resonance spectroscopy(PMRS). Ten New Zealand white rabbits were used for construction of the model of acute hemorrhagic anemia. 1H-MRS was performed before and at the time-peint of 30, 90, and 180 min after hemorrhagic shock. The concentrations of NAA, Cr, Cho, Lac, and NAA/Cr and Cho/Cr ratios were estimated. Hemorrhagic shock was associated with significant reductions in red blood cell count, hemoglobin level, hematocrit, pH, and PaCO2, and elevations of blood lactate and PaO2. The ratios of NAA/Cr at 30 min, 90 min and 180 min after shock were (1.50±0.09), (1.37±0.09) and (1.27±0.10), respectively, which were significantly lower than those before shock (2.11±0.16) (P <0.05) (1.16±0.05) and (0.97±0.04) at 30 min and 90 min after shock, respectively, which were significantly lower than those pre-shock (1.38±0.08) (P <0.05). The ratis of Cho/Cr at 30 min and 90 min were (1.16±0.05) and (0.97±0.04), respectively, which were significantly lower than those before shock (1.38±0.08) (P <0.05). MRS can noninvasively and dynamically detect brean metabolic changes in early hemorrhagic shock, and has positive significance for early diagnosis and prognosis assessment of hemorrhagic shock.

Hyperlactatemia on ICU admission : Comparison between direct admissions and inpatient transfers.

Hyperlactatemia is associated with increased mortality. Possible differences between patients directly admitted via the emergency department to the intensive care unit (ICU) and inpatient transfers to the ICU have not yet been investigated. In this retrospective analysis, characteristics and outcomes between critically ill medical inpatient transfers and direct admissions with hyperlactatemia on ICU admission, defined as ablood lactate >2 mmol/l, were compared. Atotal of 1042 patients were included, with 424 inpatient transfers and 618 direct admissions. The median age of inpatient transfers and direct admissions was 67.0 and 70.5 years, respectively (P = 0.03). The median APACHE II score was 25 for inpatient transfers and 23 for direct admissions (P = 0.01). The median blood lactate on ICU admission for inpatient transfers and direct admissions was similar (3.6 vs. 3.5 mmol/l). Sepsis was more common among inpatient transfers than direct admissions (53.5 vs. 31.6%, P = 0.001). The ICU (39.6 vs. 28.8%, P < 0.001), hospital (56.8 vs. 38.3%, P < 0.001) and 28-day mortality (46.5 vs. 35.4%, P < 0.001) was significantly higher for inpatient transfers than direct admissions. Among the sepsis cohort, inpatient transfer, APACHEII score and elevated blood lactate were independent predictors of ICU mortality. Among medical ICU patients with admission hyperlactatemia, the median blood lactate was not significantly different between direct admissions and inpatient referrals. Inpatients with sepsis may have been referred to the ICU late.

An equation to predict the maximal lactate steady state from ramp-incremental exercise test data in cycling

ObjectivesThe maximal lactate steady state (MLSS) represents the highest exercise intensity at which an elevated blood lactate concentration ([Lac]b) is stabilized above resting values. MLSS quantifies the boundary between the heavy-to-very-heavy intensity domains but its determination is not widely performed due to the number of trials required. DesignThis study aimed to: (i) develop a mathematical equation capable of predicting MLSS using variables measured during a single ramp-incremental cycling test and (ii) test the accuracy of the optimized mathematical equation. MethodsThe predictive MLSS equation was determined by stepwise backward regression analysis of twelve independent variables measured in sixty individuals who had previously performed ramp-incremental exercise and in whom MLSS was known (MLSSobs). Next, twenty-nine different individuals were prospectively recruited to test the accuracy of the equation. These participants performed ramp-incremental exercise to exhaustion and two-to-three 30-min constant-power output cycling bouts with [Lac]b sampled at regular intervals for determination of MLSSobs. Predicted MLSS (MLSSpred) and MLSSobs in both phases of the study were compared by paired t-test, major-axis regression and Bland–Altman analysis. ResultsThe predictor variables of MLSS were: respiratory compensation point (Wkg−1), peak oxygen uptake (V˙O2peak) (mlkg−1min−1) and body mass (kg). MLSSpred was highly correlated with MLSSobs (r=0.93; p<0.01). When this equation was tested on the independent group, MLSSpred was not different from MLSSobs (234±43 vs. 234±44W; SEE 4.8W; r=0.99; p<0.01). ConclusionsThese data support the validity of the predictive MLSS equation. We advocate its use as a time-efficient alternative to traditional MLSS testing in cycling.

Lactic acid suppresses LPS-induced cytokine production in mast cells by limiting glycolysis and ATP availability

Abstract Despite a mortality rate of 30–50%, there are no targeted molecular treatments for sepsis. Our understanding of the secondary immunosuppressive phase is recent, and it is unclear whether many mediators are helpful or detrimental to patient survival. Elevated blood lactate and slow lactate clearance are associated with mortality, however, any regulatory roles are currently unknown. Because mast cells can be activated systemically and contribute to sepsis, this project aims to elucidate lactic acid effects on mast cell activation and signaling. Lactic acid significantly suppressed LPS-induced cytokine and chemokine production as well as NFκB transcription in bone marrow derived and peritoneal mast cells. These effects were dependent upon pH and MCT-1 transporter activity. Further, lactic acid significantly suppressed cytokine and chemokine induction following LPS-induced septic shock in vivo. We also examined the role of lactic acid as a feedback regulator of glucose metabolism. Lactic acid treatment reduced glucose uptake, lactate export, and hexokinase 2 expression following LPS activation. The glycolytic inhibitors 2-deoxyglucose, sodium oxamate, or dichloracetate mimicked lactic acid effects, suppressing LPS-induced cytokine production and NFκB transcription. Furthermore, adding ATP to the culture media at the time of LPS activation reversed lactic acid effects. These results indicate that suppressing glycolysis and ATP production are necessary and sufficient for lactic acid effects. Future studies should target enhancing glycolysis and ATP production to improve immune function and counteract lactic acid effects in sepsis.

Increased blood lactate is prevalent and identifies poor prognosis in patients with acute heart failure without overt peripheral hypoperfusion.

Lactate is produced by anaerobic metabolism and may reflect inadequate tissue perfusion in conditions such as acute heart failure (AHF). We evaluated the prevalence and clinical significance of elevated blood lactate on admission in patients with AHF. We enrolled 237 patients with AHF (mean age 67 ± 12 years; 70% men) presenting without overt clinical evidence of peripheral hypoperfusion ('warm haemodynamic profile'). Median (upper and lower quartiles) blood lactate on admission was 1.8 (1.5; 2.4) mmol/L; 103 (43%) patients had an elevated blood lactate (≥2 mmol/L). Patients with an elevated lactate had higher blood high-sensitivity troponin I [15.4 (8.5; 26.1) vs. 9.9 (4.3; 19.6) pg/mL], aspartate aminotransferase [28 (20; 44) vs 24 (19; 36) IU/L] and endothelin-1 (12.1 ± 6.2 vs. 9.3 ± 3.9 pg/mL) (all P< 0.05). In this group plasma concentration of neutrophil gelatinase-associated lipocalin increased during the first 48 h, whereas values fell for those with normal baseline lactate [1.9 (-3.2; 9.7) vs. -1.3 (-13.9; 5.6) μg/dL; P< 0.05). One-year mortality was higher amongst patients with an elevated blood lactate (36% vs. 21%; P< 0.05). After adjustment for other well-established prognostic variables, blood lactate on admission predicted poor outcome (hazard ratio 1.24, 95% confidence interval 1.08-1.41; P< 0.05). An elevated blood lactate on admission is common in AHF patients without overt clinical evidence of peripheral hypoperfusion and is associated with markers of organ dysfunction/damage and a worse prognosis.

Post-exercise serum hepcidin levels were unaffected by hypoxic exposure during prolonged exercise sessions.

The purpose of the present study was to determine the influence of hypoxic exposure during prolonged endurance exercise sessions (79 min in total) on post-exercise hepcidin levels in trained male endurance athletes. Ten endurance athletes (mean ± standard deviation; height: 169.8 ± 7.1 cm, weight: 57.1 ± 5.0 kg) conducted two endurance exercise sessions under either a normobaric hypoxic condition [inspired O2 fraction (FiO2) = 14.5%] or a normoxic condition (FiO2 = 20.9%). Exercise consisted of 10 × 3 min running on a treadmill at 95% of maximal oxygen uptake () with 60s of active rest at 60% of . After 10 min of rest, they subsequently performed 30 min of continuous running at 85% of . Running velocities were significantly lower in the HYPO than in the NOR (P < 0.0001). Exercise-induced blood lactate elevation was significantly greater in the HYPO (P < 0.01). There were significant increases in plasma interleukin-6, serum iron, and blood glucose levels after exercise, with no significant difference between the trials [interaction (trial × time) or main effect for trial, P > 0.05]. Serum hepcidin levels increased significantly 120 min after exercise (HYPO: from 10.7 ± 9.4 ng/mL to 15.8 ± 11.2 ng/mL; NOR: from 7.9 ± 4.7 ng/mL to 13.2 ± 7.9 ng/mL, P < 0.05), and no difference was observed between the trials. In conclusion, endurance exercise at lower running velocity in hypoxic conditions resulted in similar post-exercise hepcidin elevations as higher running velocity in normoxic conditions.

Prognostic Value of Hyperlactatemia and Lactate Clearance After Mitral Valve Surgery

Blood lactate is frequently used to guide management in critically ill patients. In patients undergoing mitral valve surgery, an elevated lactate level is frequently observed; however, overall mortality is low. The authors hypothesized that hyperlactemia is not a useful predictor of poor outcomes in this patient population. The main aim of this study was to explore how blood lactate level and lactate clearance are associated with 30-day mortality and major adverse events in patients undergoing mitral valve surgery. This was a retrospective database review. Logistic regression analysis was performed to assess the associations of perioperative factors with blood lactate in the intensive care unit (ICU). Tertiary-care teaching hospital. The study comprised 917 patients undergoing mitral valve surgery. None. The majority of patients (71.8%) had elevated blood lactate ≥2 mmol/L on ICU admission; however, within 24 hours, 85.1% of all patients had normal lactate values. Overall 30-day mortality was 2.29% (n = 21). The combination of lactate ≥7 mmol/L on ICU admission and a persistent elevated blood lactate level 24 hours after ICU admission provides an excellent prediction of 30-day mortality (C statistic = 0.85). However, even a significantly elevated lactate level on ICU admission was well-tolerated in the majority of patients as long as lactate values normalized within 24 hours. Male sex, longer cardiopulmonary bypass time, blood transfusion in the ICU, and an elevated blood lactate level on ICU admission and 12 hours after ICU admission all were independent risk factors of clearance failure. An elevated blood lactate level is common after mitral valve surgery and is well-tolerated in the majority of patients. Adding lactate clearance improved the predictive value of the blood lactate level.

Assessment of Metabolic Flexibility by Means of Measuring Blood Lactate, Fat, and Carbohydrate Oxidation Responses to Exercise in Professional Endurance Athletes and Less-Fit Individuals.

Increased muscle mitochondrial mass is characteristic of elite professional endurance athletes (PAs), whereas increased blood lactate levels (lactatemia) at the same absolute submaximal exercise intensities and decreased mitochondrial oxidative capacity are characteristics of individuals with low aerobic power. In contrast to PAs, patients with metabolic syndrome (MtS) are characterized by a decreased capacity to oxidize lipids and by early transition from fat to carbohydrate oxidation (FATox/CHOox), as well as elevated blood lactate concentration [La-] as exercise power output (PO) increases, a condition termed 'metabolic inflexibility'. The aim of this study was to assess metabolic flexibility across populations with different metabolic characteristics. We used indirect calorimetry and [La-] measurements to study the metabolic responses to exercise in PAs, moderately active individuals (MAs), and MtS individuals. FATox was significantly higher in PAs than MAs and patients with MtS (p<0.01), while [La-] was significantly lower in PAs compared with MAs and patients with MtS. FATox and [La-] were inversely correlated in all three groups (PA: r=-0.97, p<0.01; MA: r=-0.98, p<0.01; MtS: r=-0.92, p<0.01). The correlation between FATox and [La-] for all data points corresponding to all populations studied was r=-0.76 (p<0.01). Blood lactate accumulation is negatively correlated with FATox and positively correlated with CHOox during exercise across populations with widely ranging metabolic capabilities. Because both lactate and fatty acids are mitochondrial substrates, we believe that measurements of [La-] and FATox rate during exercise provide an indirect method to assess metabolic flexibility and oxidative capacity across individuals of widely different metabolic capabilities.

BIOMARKERS OF SEPSIS

“Sepsis is a state caused by microbial invasion from a local infectious source into the blood stream which leads to signs of systemic illness in remote organs,” this was the first scientific definition of sepsis proposed by Dr. Schottmuller in 1914.Sepsis is among the most common causes of death in hospitalized patients. Its death toll is in the same range as that of myocardial infarction. 1 Early and reliable diagnosis is imperative, because of the remarkably rapid progression of sepsis into a life-threatening condition.2 Findings in a patient with suspected or proven infection include fever or hypothermia, tachypnea, tachycardia, leukocytosis or leucopenia, acutely altered mental status, thrombocytopenia, an elevated blood lactate level, respiratory alkalosis, or hypotensions. 3 JMS 2017; 20(1):2-4

A Case Study of Gestational Gigantomastia

Gestational gigantomastia is a rare condition characterized by rapid breast growth during pregnancy. The increased breast size leads to pain, ulceration, infection, bleeding, necrosis, and difficulty with mobility and can be fatal. Management is challenging and requires pain control, extensive wound care, psychological counseling, and surgical intervention. This case of bilateral gestational gigantomastia resulted in pregnancy termination. A 33-year-old woman presented to the quaternary academic medical center with gigantomastia at 15 weeks gestation. On presentation, her breasts were erythematous, firm, and tender. Laboratory findings included hypercalcemia; decreased intact parathyroid hormone levels; and elevated white blood cells, lactate levels, and parathyroid hormone-related protein. She reported severe constipation, anorexia, visual changes, headache, and fatigue. Diagnostic studies included abdominal and thyroid ultrasounds, chest computed tomography, and biopsy of chest wall tissue mass. Nephrolithiasis, breast hyperplasia, and axillary lymphadenopathy were confirmed. Treatment was initiated with intravenous fluids and calcitonin. The breast mass continued to grow, and she developed venous stasis ulcers that required frequent wound care. She agreed to pregnancy termination because of worsening gigantomastia and potentially poor surgical outcomes related to increased risk of hemorrhage. Interdisciplinary collaboration was imperative for provision of holistic care and successful patient outcomes. Nurse accountability for patient education and emotional support continued throughout an extensive hospitalization. Nurses supported the woman through the difficult decision to terminate her pregnancy, provided anticipatory guidance regarding probable mastectomies, and offered coping strategies for separation anxiety.

Acute Affective Responses To High-Intensity Interval Training In Trained and Untrained Men

Although exercise has been shown to alter transiently affective variables, the impact of fitness levels on affective response to high-intensity interval training (HIT) remains unclear. PURPOSE: The present study was designed to compare affective responses between HIT and continuous exercise at low-intensity in trained and untrained men. METHODS: Twenty male subjects (21.2±0.34 years) were divided into trained group [TR, n=10, maximal oxygen uptake (VO2max)55.6±1.1ml/kg/min] or untrained group (UT, n = 10, VO2max: 40.5±1.0 ml/kg/min). All subjects completed two trials in random order, consisting of HIT (10 × 1 min pedaling at 90% of VO2max) with 1 min of active rest at 30% of VO2max) or 60 min of pedaling at 50% of VO2max (LOW). Scores of muscle soreness, fatigue, vitality and desire for exercise were evaluated using visual analog scale before exercise and during 60 min of post-exercise period. Moreover, two-dimensional mood scale (TDMS) was conducted to assess vitality, stability, pleasure and arousal. Blood samples were also collected to determine blood lactate glucose concentrations. During exercise, heart rate (HR) and rating of perceived exertion (modified 10 scale) were recorded. RESULTS: Exercise-induced blood lactate elevation was significantly greater in the TR group than in the UT group (group × time, P < 0.05). The results of TDMS revealed that exercise altered significantly arousal, vitality, stability and pleasure (main effect for time, P < 0.05) after HIT and LOW. However, scores of vitality, stability and pleasure were significantly (P < 0.05) elevated 60 min after HIT in the UT group, whereas the TR group did not show similar change. CONCLUSIONS: These findings suggest that exercise improves acutely affective variables. However, the affective response to exercise appears to be particularly influenced by fitness levels, and HIT augments vitality, stability and pleasure during post-exercise period only in untrained men, not in trained men.

Clinical Features, Molecular Heterogeneity, and Prognostic Implications in YARS2-Related Mitochondrial Myopathy

YARS2 mutations have been associated with a clinical triad of myopathy, lactic acidosis, and sideroblastic anemia in predominantly Middle Eastern populations. However, the identification of new patients expands the clinical and molecular spectrum of mitochondrial disorders. To review the clinical, molecular, and genetic features of YARS2-related mitochondrial disease and to demonstrate a new Scottish founder variant. An observational case series study was conducted at a national diagnostic center for mitochondrial disease in Newcastle upon Tyne, England, and review of cases published in the literature. Six adults in a well-defined mitochondrial disease cohort and 11 additional cases described in the literature were identified with YARS2 variants between January 1, 2000, and January 31, 2015. The spectrum of clinical features and disease progression in unreported and reported patients with pathogenic YARS2 variants. Seventeen patients (median [interquartile range] age at onset, 1.5 [9.8] years) with YARS2-related mitochondrial myopathy were identified. Fifteen individuals (88%) exhibited an elevated blood lactate level accompanied by generalized myopathy; only 12 patients (71%) manifested with sideroblastic anemia. Hypertrophic cardiomyopathy (9 [53%]) and respiratory insufficiency (8 [47%]) were also prominent clinical features. Central nervous system involvement was rare. Muscle studies showed global cytochrome-c oxidase deficiency in all patients tested and severe, combined respiratory chain complex activity deficiencies. Microsatellite genotyping demonstrated a common founder effect shared between 3 Scottish patients with a p.Leu392Ser variant. Immunoblotting from fibroblasts and myoblasts of an affected Scottish patient showed normal YARS2 protein levels and mild respiratory chain complex defects. Yeast modeling of novel missense YARS2 variants closely correlated with the severity of clinical phenotypes. The p.Leu392Ser variant is likely a newly identified founder YARS2 mutation. Testing for pathogenic YARS2 variants should be considered in patients presenting with mitochondrial myopathy, characterized by exercise intolerance and muscle weakness even in the absence of sideroblastic anemia irrespective of ethnicity. Regular surveillance and early treatment for cardiomyopathy and respiratory muscle weakness is advocated because early treatment may mitigate the significant morbidity and mortality associated with this genetic disorder.