Asthma and COPD - The C/EBP Connection

Asthma and chronic obstructive pulmonary disease (COPD) are the two most prominent chronic inflammatory lung diseases with increasing prevalence. Both diseases are associated with mild or severe remodeling of the airways. In this review, we postulate that the pathologies of asthma and COPD may result from inadequate responses and/or a deregulated balance of a group of cell differentiation regulating factors, the CCAAT/Enhancer Binding Proteins (C/EBPs). In addition, we will argue that the exposure to environmental factors, such as house dust mite and cigarette smoke, changes the response of C/EBPs and are different in diseased cells. These novel insights may lead to a better understanding of the etiology of the diseases and may provide new aspects for therapies

Calreticulin Is a Negative Regulator of Bronchial Smooth Muscle Cell Proliferation

Background. Calreticulin controls the C/EBPαp42/p30 at the translational level trough a cis-regulatory CNG rich loop in the CEBPA mRNA. We determined the effects of steroids and long-acting beta-agonists on the p42/p30 ratio and on calreticulin expression in primary human bronchial smooth muscle (BSM) cells. Methods. The effects of budesonide (10−8 M) and formoterol (10−8 M) were studied in BSM cells pre-treated with siRNA targeting calreticulin. The expression of C/EBPα and calreticulin was determined by immuno-blotting. Automated cell counts were performed to measure proliferation. Results. All tested BSM cell lines (n = 5) expressed C/EBPα and calreticulin. In the presence of 5% FBS, the p42/p30 ratio significantly decreased (n = 3, P < 0.05) and coincided with BSM cell proliferation. High levels of calreticulin were associated with a decreased p42/p30 isoform ratio. FBS induced the expression of calreticulin (n = 3, P < 0.05), which was further increased by formoterol. siRNA targeting calreticulin increased the p42/p30 ratio in non-stimulated BSM cells and significantly inhibited the proliferation of PDGF-BB-stimulated BSM cells (n = 5, P < 0.05). Neither budesonide nor formoterol restored the p42 isoform expression. Conclusions. Our data show calreticulin is a negative regulator of C/EBPα protein expression in BSM cells. Modulation of calreticulin levels may provide a novel target to reduce BSM remodeling

Staged Concept for Treatment of Severe Postsaphenectomy Wound Infection

The saphenous vein remains the most commonly used conduit in coronary artery bypass surgery. Vein harvest is a critical component with significant morbidity associated with leg wounds from open technique. Occurring complications are hematoma, postoperative pain, skin changes, neuropathy, and septic or nonseptic wound complications. Within the context of a recent case, we present our approach to postsaphenectomy wound management

Turfgrass Industry Practitioners and the Pesticide Label

A seminar for green industry professionals was used to conduct a survey on the use and perception of the pesticide label. The audience was composed of those in lawn care/grounds maintenance, golf course turfgrass management, and other areas (e.g., sports turf, parks and recreation, etc.). Overall, turfgrass professionals among all three industry segments are well-informed of their responsibilities for the legal and safe use of pesticides, although industry personnel could improve their practice of keeping up with pesticide label changes and revisions

Safety and Efficacy of Hospital Utilization of Tranexamic Acid in Civilian Adult Trauma Resuscitation

Introduction: Patients with trauma-induced coagulopathies may benefit from the use of antifibrinolytic agents, such as tranexamic acid (TXA). This study evaluated the safety and efficacy of TXA in civilian adults hospitalized with traumatic hemorrhagic shock.Methods: Patients who sustained blunt or penetrating trauma with signs of hemorrhagic shock from June 2014 through July 2018 were considered for TXA treatment. A retrospective control group was formed from patients seen in the same past five years who were not administered TXA and matched based on age, gender, Injury Severity Score (ISS), and mechanism of injury (blunt vs penetrating trauma). The primary outcome of this study was mortality measured at 24 hours, 48 hours, and 28 days. Secondary outcomes included total blood products transfused, hospital length of stay (LOS), intensive care unit LOS, and adverse events. We conducted three pre-specified subgroup analyses to assess outcomes of patients, including (1) those who were severely injured (ISS &gt;15), (2) those who sustained significant blood loss (≥10 units of total blood products transfused), and (3) those who sustained blunt vs penetrating trauma.Results: Propensity matching yielded two cohorts: the hospital TXA group (n = 280) and a control group (n = 280). The hospital TXA group had statistically lower mortality at 28 days (1.1% vs 5%, odds ratio [OR] [0.21], (95% confidence interval [CI], 0.06, 0.72)) and used fewer units of blood products (median = 4 units, interquartile range (IQR) = [1, 10] vs median=7 units, IQR = [2, 12.5] for the hospital TXA and control groups, respectively, (95% CI for the difference in median, -3 to -1). There were no statistically significant differences between groups with regard to 24-hour mortality (1.1% vs 1.1%, OR = 1, 95% CI, 0.20, 5.00), 48-hour mortality (1.1% vs 1.4%, OR [0.74], 95% CI, 0.17, 3.37), hospital LOS (median= 9 days, IQR = (5, 16) vs median =12 days IQR = (6, 22.5) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-5 to 0)), and incidence of thromboembolic events (eg, deep vein thrombosis, pulmonary embolism) during hospital stay (0.7% vs 0.7% for the hospital TXA and control group, respectively, OR [1], 95% CI, 0.14 to 7.15). We conducted subgroup analyses on patients with ISS&gt;15, patients transfused with ≥10 units of blood products, and blunt vs penetrating trauma. The results indicated lower 28-day mortality for ISS&gt;15 (1.8% vs 7.1%, OR [0.23], 95% CI, 0.06 to 0.81) and blunt trauma  (0.6% vs 6.3%, OR [0.09], 95% CI, 0.01 to 0.75); fewer units of blood products for penetrating trauma (median = 2 units, IQR = (1, 8) vs median = 8 units, IQR = (5, 15) for the hospital TXA and control groups, respectively, 95% CI for the difference in median = (-6 to -3)), and ISS&gt;15 (median = 7 units, IQR = (2, 14) vs median = 8.5 units, IQR = (4, 16) for the hospital TXA and control groups, respectively, 95% CI for the difference in median, -3 to 0).Conclusion: The current study demonstrates a statistically significant reduction in mortality after TXA administration at 28 days, but not at 24 and 48 hours, in patients with traumatic hemorrhagic shock

Skeletonization of bilateral internal thoracic artery grafts lowers the risk of sternal infection in patients with diabetes

AbstractObjectiveDeep sternal wound infection is a dreaded complication of coronary artery bypass surgery, particularly in patients with diabetes. This study determines whether skeletonization of internal thoracic artery conduits compared with pedicled harvesting reduces the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting.MethodsWe reviewed prospectively gathered data on all patients who have undergone coronary artery bypass grafting and received bilateral internal thoracic artery grafts at our institution since 1990. We compared patients with diabetes who received skeletonized (n = 79) versus conventional pedicled (n = 36) internal thoracic artery conduits.ResultsThe proportion of patients taking insulin (19.0% vs 14.0% for skeletonized vs conventional grafts, respectively, P = .6) or oral hypoglycemic agents (68.4% vs 69.4%, P = .9), as well as the prevalence of type I diabetes (2.5% vs 8.3%, P = .18), were similar in both groups. Patients who received skeletonized grafts were more likely to receive a free rather than an in situ right internal thoracic artery graft (93.7% vs 30.6%, P < .001). The prevalence of deep sternal wound infection was significantly lower in patients who received skeletonized grafts compared with patients who received conventional grafts (1.3% vs 11.1%, P = .03). Patients in the skeletonized group were also less likely to develop any (superficial or deep) sternal wound infection postoperatively (5.1% vs 22.2%, P = .03). There was no significant difference in the prevalence of deep sternal wound infection between patients with diabetes who received skeletonized internal thoracic arteries and patients without diabetes who underwent conventional internal thoracic artery grafting (n = 578) (1.2% vs 1.6%, respectively, P = .8).ConclusionsSkeletonization of internal thoracic artery conduits lowers the risk of deep sternal wound infection in patients with diabetes undergoing bilateral internal thoracic artery grafting. We no longer consider diabetes a contraindication to bilateral internal thoracic artery grafting, provided the internal thoracic arteries are skeletonized

Improving mitral valve coaptation with adjustable rings: outcomes from a European multicentre feasibility study with a new-generation adjustable annuloplasty ring system†

OBJECTIVES To evaluate the performance and safety of an adjustable semi-rigid annuloplasty ring for mitral regurgitation (MR) in a multicentre study. METHODS Between March 2010 and December 2011, 30 subjects underwent mitral valve (MV) repair using the Cardinal adjustable annuloplasty ring. This device is a semi-rigid ring allowing postimplantation size adjustment, under beating-heart conditions, to optimize leaflet coaptation under echocardiographic guidance. Coaptation length was determined before and after adjustment by transoesophageal echocardiography. RESULTS The study enrolled 21 (70%) male and 9 (30%) female subjects with a mean age of 64 years. The approach was conventional midline sternotomy or mini-invasive right thoracotomy. Leaflet resection was done in 17 subjects, and chordal repair was used in 13. Concomitant procedures included coronary artery bypass grafting in 2 (7%) subjects, atrial ablation in 4 (13%) and tricuspid repair in 4 (13%). There was 1 (3%) early death unrelated to the study device. Intraoperative ring adjustment was performed in 24 of the 30 subjects. Residual MR was detected prior to adjustment in 6 subjects (4 mild and 2 moderate MR). Following adjustment, 5 subjects had no MR and 1 had trace MR. After adjustment, mean coaptation length improved from 7 ± 3 to 10 ± 3 mm (P < 0.0001). All patients who completed 1-year follow-up had less-than-mild MR, with the exception of 1 patient with ring dehiscence (and resultant 2+ MR) and 1 functional MR patient who developed recurrent 2+ MR due to persistent leaflet tethering. CONCLUSIONS MV repair with the Cardinal adjustable annuloplasty ring is a reliable technique that enables the adjustment of the ring diameter on a beating heart under echocardiographic control. Such technology allows the optimization of leaflet coaptation, providing minimal residual MR and durable repai