Effectiveness of Physical Therapy Combined With Epidural Steroid Injection for Individuals With Lumbar Spinal Stenosis: A Randomized Parallel-Group Trial

Objective

To examine the effectiveness of epidural steroid injection (ESI) and back education with and without physical therapy (PT) in individuals with lumbar spinal stenosis (LSS).

Greater chronic morbidity is associated with greater fatigue in six countries: A case of evolutionary mismatch?

Background and objectivesHuman susceptibility to chronic non-communicable disease may be explained, in part, by mismatches between our evolved biology and contemporary environmental conditions. Disease-induced fatigue may function to reduce physical activity during acute infection, thereby making more energy available to mount an effective immune response. However, fatigue in the context of chronic disease may be maladaptive because long-term reductions in physical activity increase risks of disease progression and the acquisition of additional morbidities. Here, we test whether cumulative chronic morbidity is associated with subjective fatigue.MethodologyWe constructed a cumulative chronic morbidity score using self-reported diagnoses and algorithm-based assessments, and a subjective fatigue score based on four questionnaire items using cross-sectional survey data from the Study on global AGEing and adult health, which features large samples of adults from six countries (China, Ghana, India, Mexico, Russia and South Africa).ResultsIn a mixed-effects linear model with participants nested in countries (N = 32 455), greater cumulative chronic morbidity is associated with greater subjective fatigue (β = 0.34, SE = 0.005, P < 2e−16). This association replicates within each country and is robust to adjustment for key sociodemographic and physical covariates (sex, age, household wealth, physical function score, habitual physical activity, BMI and BMI²).Conclusions and implicationsFatigue is a common but perhaps maladaptive neuropsychological response to chronic morbidity. Disease-induced fatigue may mediate a self-perpetuating cycle, in which chronic morbidity reduces physical activity, and less physical activity increases cumulative chronic morbidity. Longitudinal research is needed to test whether chronic morbidity, fatigue and physical activity form a cyclical feedback loop. Lay Summary: Fatigue during acute illness may promote recovery, but persistent fatigue in the context of chronic disease may make matters worse. We present evidence from six countries that more chronic disease is associated with more fatigue. This fatigue may reduce physical activity, which increases risks of acquiring additional chronic health problems.     

Susceptibility weighted imaging: neuropsychologic outcome and pediatric head injury

Traumatic brain injury is among the most frequent pediatric neurologic disorders in the United States, affecting multiple aspects of neuropsychologic functioning. This study assessed the efficacy of susceptibility weighted imaging as a predictor of long-term neuropsychologic functioning after pediatric brain injury compared with magnetic resonance spectroscopic imaging. Susceptibility weighted imaging is a relatively new method that is considered superior to traditional magnetic resonance imaging sequences for detecting hemorrhagic diffuse axonal injury. In this study, imaging and spectroscopy were acquired 6 +/- 4 days after injury. Measures of neuropsychologic functioning were administered to 18 children and adolescents 1-4 years post injury. Negative correlations between lesion number and volume with neuropsychologic functioning were demonstrated. Lesion volume explained over 32% of the variance in cognitive performance, explaining at least an additional 20% beyond injury severity and age at injury alone and 19% beyond magnetic resonance spectroscopic metabolite variables. Exploratory analyses resulted in notable trends, with lesions in deeper brain regions more strongly associated with poorer neuropsychologic performance. Improved detection of the extent of diffuse axonal injury following a brain injury will allow for a better understanding of its association with long-term outcome, which in turn can improve prognostic efficacy for effective treatment planning.     

Practices and attitudes towards radiation risk disclosure for computed tomography: survey of emergency medicine residency program directors

Purpose

The purposes of this study were to evaluate the frequency with which emergency physicians involved in residency leadership disclose potential malignancy risks from computed tomography (CT), assess comfort with these discussions, and evaluate factors influencing risk disclosure.

Methods

We surveyed emergency medicine residency program directors and associate/assistant directors. Primary outcome was the proportion who “almost always” or “most of the time” discussed potential risks.

Results

Two hundred and seventy-four (50.6%) of 542 eligible physicians responded. There were 82.1% (95% CI 76.8%, 86.6%) who reported almost always or most of the time discussing potential risks for patients ≤18 years; proportions for adults 19–40, 41–65, and >65 years were 50.6% (95% CI 44.4, 56.7%), 20.7% (95% CI 16.0, 26.0%), and 5.2% (95% CI 2.9, 8.5%), respectively (test for trend, p < 0.001). The proportion reporting being “extremely” or “very” comfortable discussing risks was 57.1% (95% CI 51.1, 63.2%). Patient/family CT request that the physician felt was not indicated was of “very high” or “high” importance for driving risk discussions in 86.4% of respondents. For 75.5%, patient/family query about radiation risks was of “high” or “very high” importance. Among 57.4% of respondents, the patient being elderly and/or having a reduced life expectancy was of “high” or “very high” importance in the decision not to discuss risk.

Conclusions

Emergency physicians involved in residency leadership report frequently disclosing potential malignancy risks from CT at frequencies inversely proportional to patient age. About half are comfortable with discussions, and many discussions are driven by patient requests. Opportunities exist to optimize and standardize emergency department CT radiation risk disclosure practices.

     

Análisis de los factores de influencia sobre el resultado de 500 ciclos de inseminación intrauterina homóloga

Objective

To evaluate the results and analyse different factors influencing pregnancy rate using homologous intrauterine insemination.

Subjects and methods

Retrospective analysis of 500 homologous intrauterine insemination cycles in 183 infertile couples. Only one insemination per stimulated ovarian cycle was performed in patients with: mild endometriosis, ovulatory factor, male subfertility or unexplained infertility. We studied female age, duration of infertility, stimulation protocol, number of cycle, number of preovulatory follicles, motile sperm count and endometrial thickness related to pregnancy rate.

Results

Pregnancy rate per couple was 24% and per intrauterine insemination 9%, 11% was multiple pregnancies. Best outcome has been got in women younger than 37 years (P=.048) and in cycles with more than one preovulatory follicle. Other studied factors did not have influence in homologous intrauterine insemination outcome.

Conclusions

Female age is a prognostic factor for homologous intrauterine insemination with poor outcome in women older than 38 years. Cycles with more than one preovolatory follicle have better outcome. No differences in pregnancy rate have been achieved with motile sperm count over 1.5 millions/0.3 ml.     

Metabolic assessment of the brain using proton magnetic resonance spectroscopy in a growth-restricted human fetus: case report

Proton magnetic resonance spectroscopy (MRS) is a noninvasive method to assess concentrations of different metabolites in tissues, including the brain. We evaluated a fetus with growth restriction using Doppler ultrasound and proton MRS. Doppler assessment revealed absent end diastolic flow in the umbilical artery. Diastolic flow was increased in the middle cerebral artery. Proton MRS of the fetal brain showed lactate and a low N-acetylaspartate/choline index, metabolic markers of starvation/hypoxia. Proton MRS gave us in vivo metabolic information of the brain of a fetus under starvation/hypoxic conditions. It is potentially a new tool for fetal surveillance. To our knowledge, this is the first report of cerebral lactate detection using proton MRS in a growth-restricted human fetus with no associated malformations in the English literature. Further experimental and clinical longitudinal investigations are needed to evaluate its efficacy in the clinical setting.     

Apratoxin D, a potent cytotoxic cyclodepsipeptide from papua new guinea collections of the marine cyanobacteria Lyngbya majuscula and Lyngbya sordida

Cancer cell toxicity-guided fractionation of extracts of the Papua New Guinea marine cyanobacteria Lyngbya majuscula and Lyngbya sordida led to the isolation of apratoxin D (1). Compound 1 contains the same macrocycle as apratoxins A and C but possesses the novel 3,7-dihydroxy-2,5,8,10,10-pentamethylundecanoic acid as the polyketide moiety. The planar structures and stereostructures of compound 1 were determined by extensive 1D and 2D NMR and MS data analyses and by comparison with the spectroscopic data of apratoxins A and C. Apratoxin D (1) showed potent in vitro cytotoxicity against H-460 human lung cancer cells with an IC 50 value of 2.6 nM.     

Fetal adrenal gland volume and cortisol/dehydroepiandrosterone sulfate ratio in inflammation-associated preterm birth

OBJECTIVE: Fetal adaptation to stress is regulated in part by the pituitary-adrenocortical system. The stress hormones dehydroepiandrosterone sulfate (DHEAS) and cortisol have opposing effects: cortisol suppresses while DHEAS enhances immune functions. We sought to estimate the impact of intraamniotic inflammation on fetal adrenal gland volume and cortisol-to-dehydroepiandrosterone sulfate ratio (fetal stress ratio) in pregnancies complicated by preterm birth. METHODS: Fifty-one consecutive singleton fetuses of mothers who had an indicated amniocentesis to rule out infection were analyzed. Intraamniotic inflammation was assessed by proteomic profiling of amniotic fluid for the biomarkers of the Mass Restricted score. The Mass Restricted score ranges from 0 (biomarkers absent) to 4 (all biomarkers present), with Mass Restricted scores of 3 or 4 indicating severe intraamniotic inflammation. Fetal adrenal gland volume was assessed by three-dimensional ultrasonography and corrected for estimated fetal weight. Interleukin-6 (IL-6), cortisol, and DHEAS were measured by immunoassay. RESULTS: Women with intraamniotic inflammation delivered earlier (27.8+/-3.4 weeks, n=16, compared with 32.3+/-3.0 weeks, n=35, P<.001), and their fetuses had higher cord blood IL-6 (P=.011) and higher corrected adrenal gland volumes (P=.027). Cord blood IL-6 levels were in direct relationship with corrected adrenal volume (r=0.372, P=.019), fetal cortisol (r=0.428, P=.010), and DHEAS (r=0.521, P<.001). However, fetuses exposed to intraamniotic inflammation had an overall lower fetal stress ratio (P=.034). These results maintained after adjusting for gestational age, uterine contractions, and steroid exposure. CONCLUSION: Fetuses exposed to intraamniotic inflammation have higher adrenal gland volumes and lower cortisol-to-DHEAS ratios, suggesting that the fetal adrenocortical axis plays a role in the intrauterine adaptation to inflammation.     

Therapeutic targets for cardiac fibrosis: from old school to next-gen

Cardiovascular diseases remain the leading cause of death worldwide, with pathological fibrotic remodeling mediated by activated cardiac myofibroblasts representing a unifying theme across etiologies. Despite the profound contributions of myocardial fibrosis to cardiac dysfunction and heart failure, there currently exist limited clinical interventions that effectively target the cardiac fibroblast and its role in fibrotic tissue deposition. Exploration of novel strategies designed to mitigate or reverse myofibroblast activation and cardiac fibrosis will likely yield powerful therapeutic approaches for the treatment of multiple diseases of the heart, including heart failure with preserved or reduced ejection fraction, acute coronary syndrome, and cardiovascular disease linked to type 2 diabetes. In this Review, we provide an overview of classical regulators of cardiac fibrosis and highlight emerging, next-generation epigenetic regulatory targets that have the potential to revolutionize treatment of the expanding cardiovascular disease patient population.