Surgery for a fracture of the hip within 24 hours of admission is independently associated with reduced short-term post-operative complications.

AIMS: We aimed to characterise the effect of expeditious hip fracture surgery in elderly patients within 24 hours of admission on short-term post-operative outcomes. PATIENTS AND METHODS: Patients age 65 or older that underwent surgery for closed femoral neck and intertrochanteric hip fractures were identified from the American College of Surgeons National Surgical Quality Improvement Program between 2011 and 2014. Multivariable propensity-adjusted logistic regressions were performed to determine associations between early surgery within 24 hours and post-operative complications, controlling for selection bias in patients undergoing early surgery based on observable characteristics. RESULTS: A total of 26 051 patients were included in the study; 5921 (22.7%) had surgery within 24 hours of admission, while 20 130 (77.3%) patients had surgery after 24 hours. Propensity-adjusted multivariable logistic regressions demonstrated that surgery within 24 hours was independently associated with lower odds of respiratory complications including pneumonia, failure to extubate, or reintubation (odds ratio (OR) 0.78, 95% confidence interval (CI) 0.67 to 0.90), and extended length of stay (LOS) defined as ≥ 6 days (OR 0.84, 95% CI 0.78 to 0.90). CONCLUSION: In elderly patients with hip fractures, early surgery within 24 hours of admission is independently associated with less pulmonary complications including pneumonia, failure to extubate, and reintubation, as well as shorter LOS. Cite this article: Bone Joint J 2017;99-B:1216-22.

Heterogeneous cellular expression of creatine kinase isoenzyme during normal rat heart development.

The degree to which developmentally related alterations in cardiac creatine kinase (CK) activity reflect modification of CK isoenzyme gene expression remains uncertain. The present studies addressed this question by assessing multiple aspects of CK in rat heart during the perinatal to adult transition. In addition to whole tissue, isolated and purified muscle and nonmuscle cells were studied, as well as myofibrillar, mitochondrial, and cytosolic subcellular fractions. Whole homogenate CK enzyme specific activity nearly doubled during the weanling to adult developmental period. Muscle cell CK activity increased by a similar magnitude. Nonmuscle cell activity decreased. In the adult heart, both myofibrillar and mitochondrial CK activities were augmented versus the weanling heart. The cytoplasmic fraction activity held constant during development. Electrophoretic isoenzyme analyses of both weanling and adult cardiac muscle cells indicated the presence of mitochondrial CK and MM-CK isoforms. Weanling heart nonmuscle cells contained mitochondrial, MM, MB, and BB isoforms; however, BB isoform was not detected in the adult heart nonmuscle cells. Arrhenius plots provided information regarding heart muscle and nonmuscle cell alterations during development. CK activation energies were also determined for whole tissue, muscle/nonmuscle cells, myofibrils, mitochondria, and cytosol. Results demonstrate that heterogeneous muscle/nonmuscle cellular composition and differential myofibrillar/mitochondrial subcellular composition account for normal, developmentally related changes in heart CK enzyme activity. CK isoenzyme gene expression changes were not detected in cardiac muscle cells, and transition of CK-B to CK-M gene expression is limited to nonmuscle cells during normal, weanling to adult development in the rat heart.

Enzymatic method for quantitating creatine kinase M and B isoenzyme composition in cardiac tissue: consideration for utilization in studies of developing and adult rat heart.

Creatine kinase (CK) is a cardiac enzyme of interest due to its involvement in both mitochondrial and contractile protein aspects of heart function. Studies on the structure, function, and developmental expression of myofibrillar CK led to the identification of specific isoenzymes whose synthesis can be mediated by changes in expression at two primary gene loci. Experimental interventions which alter gene expression and protein synthesis in other cardiac enzymes have been attempted to pinpoint underlying genetic and molecular CK control mechanisms. CK isoenzymes can be separated electrophoretically and then quantitated by densitometry; however, these methods are time consuming and require specialized instruments. Enzyme specific activity can be assessed spectrophotometrically, but this method, alone, does not provide isoenzyme quantitation. The present work establishes a rapid, simple spectrophotometric enzyme assay procedure based on relative thermal lability to quantitate tissue CK isoenzyme composition. Applicability to cardiac tissue having (a) heterogeneous muscle/nonmuscle cells and (b) heterogeneous subcellular fractions within a given cell population was evaluated. Results show that cardiac tissue from newborn, weanling, and adult rats undergoes dramatic and progressive augmentation of overall CK enzyme activity that may be mediated, at least in part, by altered CK gene expression. However, based on adult rat heart analyses, it is also apparent that cell makeup and fractional composition of subcellular constituents require consideration. The described activation energy method is simple, rapid, and reliable for initial screening for potential changes in CK isoenzyme expression which can then be verified by more detailed, albeit more complex, methodology involving mRNA and/or cDNA analyses.

Enzymatic method for quantitating lactate dehydrogenase isoenzyme composition in cardiac tissue: utilization of the method to characterize newborn and adult rat heart.

Lactate dehydrogenase (LDH) is an enzyme of special interest due to its key position in anaerobic metabolic pathways. Work on the structure and developmental expression of LDH led to formulation of the isoenzyme concept as well as elucidation of the biological significance of isoenzymes. Tissue isoenzyme compositional changes are mediated by changes in pattern of gene expression for two primary LDH gene loci in vertebrates. Developmental shifts in LDH gene expression prompted other experimental interventions to alter gene expression schedule and enzyme synthesis in order to pinpoint underlying genetic and molecular control mechanisms. LDH isoenzymes in tissues can be separated by electrophoresis and then quantitated by scanning densitometry; however, these methods require specialized instruments. Enzyme specific activity can be assessed spectrophotometrically, but enzymatic activity determination alone does not provide quantitation of LDH isoenzyme(s). The present work was conducted to establish a spectrophotometric enzyme assay procedure based on differential substrate inhibition to quantitate tissue LDH isoenzymes. The procedure was then used to assess developmentally related alterations in LDH isoenzymes in cardiac tissue of newborn and young adult rats. Results show that heart tissue in 5-day old newborn rats possesses approximately equal proportions of muscle type (anaerobic) and cardiac type (aerobic) LDH isoforms. As normal development transpires, heart tissue LDH isoenzyme proportion shifts with substantial decrease in anaerobic form which is accompanied by marked augmentation in aerobic form.

Perinatal enhancement of cardiac myofibrillar creatine kinase activity without change in enzyme Km.

Myofibrillar creatine kinase (CK) serves as one microcompartment of the phosphorylcreatine shuttle by providing ATP as substrate for adenosinetriphosphatase (ATPase). During perinatal heart development, augmentations of myofibrillar ATPase and CK occur in concert with increased contractile performance. The maximal reaction velocity (Vmax) for CK doubles during development in both intact native myofibril and enzyme extracted from myofibril. The absence of alterations in ADP and creatine phosphate substrate Michaelis constants (Km), isoenzyme composition, or total number of -SH groups suggests active site function (Vmax) is influenced indirectly via a subunit domain effect on enzyme conformation.

Cardiac myofibrillar creatine kinase Km is not influenced by contractile protein binding.

Subcellular microcompartmentation underlies the proposed phosphorylcreatine shuttle mechanism in mammalian cardiac tissue. In mitochondria, CK coupling to oxidative phosphorylation via adenine nucleotide translocase decreases the Km for ATP and suggests both a functional and physical integration. In the present studies, substrate Km of myofibrillar CK was unaltered when determined in the intact, native state or after removal from the myofibril. In contrast to mitochondria, close spatial proximity between cardiac myofibrillar CK and ATPase is sufficient to establish phosphorylcreatine shuttle microcompartmentation.

The relationship between systolic anterior motion of the mitral valve and the left ventricular outflow tract Doppler in hypertrophic cardiomyopathy.

In an attempt to investigate the role of left ventricular blood outflow in the generation of systolic anterior motion (SAM) of the mitral valve in patients with hypertrophic cardiomyopathy, we precisely analyzed the temporal relation of SAM and the left ventricular outflow tract (LVOT) systolic Doppler events obtained at the maximal mitral-septal apposition or equivalent area in eight patients with severe SAM, in five patients with mild/moderate SAM, and in seven patients with no SAM, using M-mode and pulsed Doppler echocardiography; the results were compared with those in 10 normal subjects. In all 13 patients with SAM, the timing of SAM generation corresponded to the LVOT Doppler events either between the onset of SAM and the onset of Doppler (r = 0.834, p less than 0.0001) or between the peak of SAM and the peak of Doppler (r = 0.836, p less than 0.0001). The excursion rate of the development of SAM showed a correlation with the LVOT blood outflow acceleration (r = 0.828, p less than 0.0001). The timing of SAM resolution also correlated with the Doppler events, either between the offset of SAM and the offset of Doppler (r = 0.795, p less than 0.001) or the end of SAM and the end of Doppler (r = 0.859, p less than 0.0001). The LVOT blood outflow deceleration showed a correlation with the regression rate of SAM (r = 0.668, p less than 0.013). The LVOT blood outflow acceleration was significantly higher in patients with severe SAM than in patients with mild/moderate SAM or no SAM. This study suggests that the high LVOT blood outflow acceleration in early systole possibly plays an important part in the generation of the Bernoulli pressure drop and results in anterior motion of the mitral valve. At mid-systole, a drag force and/or suction effect of pressure drop produced by continuous outflow blood may sustain the anterior motion of the mitral valve. At late systole, as the blood flow decelerates, the regression of SAM then occurs.

Increased neutrophil myeloperoxidase activity associated with cigarette smoking.

Neutrophils from 49 young male smokers contained significantly higher myeloperoxidase (MPO) activity than those from 49 age-matched, nonsmoking controls, while the elastase-like activity was not different in the two populations. MPO activity was increased in some smokers, but did not correlate significantly with the increased number of peripheral blood neutrophils, cigarette usage (present or cumulative), or the mild pulmonary dysfunction detected by forced expiratory spirometry and the single breath nitrogen test. This increased MPO activity in smokers' neutrophils may contribute to the greater risk of obstructive pulmonary disease in some smokers by an exacerbation of the protease-antiprotease imbalance in the lung. This hypothesis is supported by the prior observations that neutrophils are recruited in greater numbers into the lungs of smokers and that MPO (in the presence of H2O2 and chloride ion) oxidatively inactivates antiproteases of both the alveoli and the mucus-lined airways.