Citations

Immunostains are used to subtype hepatic adenomas to stratify for the risk of malignant transformation. The most common panel of immunostains used for this purpose includes liver fatty acid–binding protein (LFABP), serum amyloid A (SAA) protein, C-reactive protein (CRP), and glutamine synthetase (GS). Importantly, some pathologists use these stains in an attempt to distinguish hepatocellular carcinomas (HCC) from hepatic adenomas. However, there are limited data on the performance of these stains in HCCs. To investigate the staining characteristics of HCCs, we studied 159 HCCs (92 well-differentiated, 67 moderately differentiated, and 7 poorly differentiated) and 7 fibrolamellar carcinomas for the expression of LFABP, SAA, CRP, and GS. All of the stains were positive in at least a subset of HCCs: SAA was positive in 27 of 159 (17%), CRP in 86 of 159 (54%), and GS in 23 of 47 (49%) cases; LFABP showed loss of staining in 36 of 159 (23%) cases. Fibrolamellar carcinomas were consistently CRP positive (7 of 7 cases) and frequently showed loss of LFABP (4 of 7 cases). There was no association between expression of SAA, CRP, and GS as well as loss of LFABP expression and other clinicopathologic features. HCCs with loss of LFABP were more frequently associated with negative GS expression (11 of 14 cases, P =0.02). These data show that immunostains used to subtype hepatic adenomas are not useful for distinguishing HCCs from hepatic adenomas and should be used only after a diagnosis of hepatic adenoma has been made using other criteria.

Background: The incidence of isolated anterior cruciate ligament (ACL) tears in the general population is not well defined. Purpose/Hypothesis: The purpose of this study was to define the population-based incidence of ACL tears, describe trends in ACL injuries over time, and evaluate changes in the rate of surgical management. The hypothesis was that the incidence of ACL injury and the rate of subsequent ACL reconstruction increase over time. Study Design: Cohort study; Level of evidence, 3. Methods: The study population included 1841 individuals who were diagnosed with new-onset, isolated ACL tears (without concomitant ligament injury that required surgery) between January 1, 1990, and December 31, 2010. The complete medical records were reviewed to confirm diagnosis and to extract injury and treatment details. Age- and sex-specific incidence rates were calculated and adjusted to the 2010 US population. Poisson regression analyses were performed to examine incidence trends by age, sex, and calendar period. Results: The overall age- and sex-adjusted annual incidence of ACL tears was 68.6 per 100,000 person-years. Incidence was significantly higher in male patients than in females (81.7 vs 55.3 per 100,000, P < .001). The incidence of isolated ACL tears decreased significantly over time in males ( P < .001) but remained relatively stable in females. Age-specific patterns differed in male and female patients, with a peak in incidence (241.0 per 100,000) between 19 and 25 years in males and a peak in incidence (227.6 per 100,000) between 14 and 18 years in females. The rate of ACL reconstruction increased significantly over time in all age groups ( P < .001). Conclusion: With an annual incidence of 68.6 per 100,000 person-years, isolated ACL tears remain a common orthopaedic injury. Differences in age-specific incidence trends in male and female patients may potentially reflect differences in sports participation patterns through the high school and college years. The significant increase in the rate of ACL reconstruction over time may reflect changing surgical indications or an increasing desire among patients to return to high levels of activity after ACL injury.

Clinical introduction An asymptomatic 29-year-old woman presented for prenatal counselling. She had a history of a heart murmur since childhood and a previous echocardiogram suggesting ‘enlargement of the heart’. Physical exam revealed normal jugular venous pressure and contour. Precordial palpation was unremarkable. Auscultation, however, was abnormal; findings on inspiration and expiration are presented in Figure 1, sound clip. Question Based on the phonocardiogram and online supplementary audio clip, which of the following is correct? An early diastolic filling sound (S3) is heard, indicating increased right ventricular filling pressures. An ejection click without respiratory variation and a systolic ejection murmur are heard, consistent with bicuspid aortic valve stenosis. An ejection click with respiratory variation and a systolic ejection murmur are heard, consistent with pulmonic valve stenosis. A holosystolic murmur with inspiratory augmentation is heard, indicating tricuspid regurgitation.

There is limited knowledge regarding the consequences of hyperinsulinemia on the lung. Given the increasing prevalence of obesity, insulin resistance, and epidemiological associations with asthma, this is a critical lacuna, more so with inhaled insulin on the horizon. Here, we demonstrate that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly ( P < 0.05) increased the proliferation of primary human airway smooth muscle (ASM) cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial respiration upon insulin exposure. Mice administered intranasal insulin showed increased collagen deposition in the lungs as well as a significant increase in airway hyperresponsiveness. PI3K/Akt mediated activation of β-catenin, a positive regulator of epithelial-mesenchymal transition and fibrosis, was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development of asthma-like phenotype.

AbstractThe Patient‐Centered Outcomes Research Institute (PCORI) was established by Congress in 2010 to promote the conduct of research that could better inform patients in making decisions that reflect their desired health outcomes. PCORI has established five national priorities for research around which specific funding opportunities are issued: 1) assessment of prevention, diagnosis, and treatment options; 2) improving healthcare systems; 3) communication and dissemination research; 4) addressing disparities; and 5) improving methods for conducting patient‐centered outcomes research. To date, implementation of patient‐centered research in the emergency care setting has been limited, in part because of perceived challenges in meeting PCORI priorities such as the need to focus on a specific disease state or to have planned follow up. We suggest that these same factors that have been seen as challenges to performing patient‐centered research within the emergency setting are also potential strengths to be leveraged to conduct PCORI research. This paper explores factors unique to patient‐centered emergency care research and highlights specific areas of potential alignment within each PCORI priority.

SummarySleep contributes importantly to energy homeostasis, and may impact hormones regulating appetite, such as leptin, an adipocyte‐derived hormone. There is increasing evidence that sleep duration, and reduced rapid eye movement sleep, are linked to obesity. Leptin has central neural effects beyond modulation of appetite alone. As sleep is not a unifrom process, interactions between leptin and sleep stages including rapid eye movement sleep may play a role in the relationship between sleep and obesity. This study examined the relationship between serum leptin and rapid eye movement sleep in a sample of healthy adults. Participants were 58 healthy adults who underwent polysomnography. Leptin was measured before and after sleep. It was hypothesized that a lower percentage of rapid eye movement sleep would be related to lower leptin levels during sleep. The relationship between percentage of rapid eye movement sleep and leptin was analysed using hierarchical linear regression. An increased percentage of rapid eye movement sleep was related to a greater reduction in leptin during sleep even when controlling for age, gender, percent body fat and total sleep time. A greater percentage of rapid eye movement sleep was accompanied by more marked reductions in leptin. Studies examining the effects of selective rapid eye movement sleep deprivation on leptin levels, and hence on energy homeostasis in humans, are needed.