Prolonged exposure to simulated microgravity diminishes dendritic cell immunogenicity.

Immune dysfunction due to microgravity remains a hurdle in the next step of human space exploration. Dendritic cells (DC) represent a critical component of immunity, given their role in the detection of invaders and the subsequent task of activating T cells to respond and eliminate the threat. Upon encounter with microbes, DC undergo a process of maturation, whereby the cells upregulate the expression of surface proteins and secrete cytokines, both required for the optimal activation of CD4+ and CD8+ T cells. In this study, DC were cultured from 2-14 days in a rotary cell culture system, which generates a simulated microgravity (SMG) environment, and then the cells were assessed for maturation status and the capacity to activate T cells. Short-term culture (<72 h) of DC in SMG resulted in an increased expression of surface proteins associated with maturation and interleukin-6 production. Subsequently, the SMG exposed DC were superior to Static control DC at activating both CD4+ and CD8+ T cells as measured by interleukin-2 and interferon-γ production, respectively. However, long-term culture (4-14 d) of DC in SMG reduced the expression of maturation markers and the capacity to activate T cells as compared to Static DC controls.

Adjuvant Lymphatic Osteopathic Manipulative Treatment in Patients With Lower-Extremity Ulcers: Effects on Wound Healing and Edema.

CONTEXT: In 2012, the US wound registry estimated that the cost of managing chronic wounds in the United States exceeded $50 billion. A large percentage of these wounds are venous stasis ulcers of the lower extremity. Evidence suggests that adjuvant osteopathic manipulative treatment (OMT) may provide a benefit by reducing edema and subsequent healing times in venous stasis ulcers of the lower extremity. OBJECTIVE: To determine whether a lymphatic OMT protocol improves wound healing rates among patients with lower-extremity edema. METHODS: This pilot study was a nonrandomized before-after community trial of lymphatic OMT in patients with lower-extremity wounds and edema. Wound surface area measurements for the preliminary phase were obtained retrospectively. During the intervention period, patients received 10 minutes of OMT twice per week. The OMT protocol, which aimed to improve lymphatic flow, included myofascial thoracic outlet release, doming of the diaphragm, pelvic diaphragm release, popliteal release, and pedal pump (2-3 minutes of continuous pump) performed in sequence. Rates of wound healing were compared between the preliminary (standard therapy), intervention (standard therapy plus OMT), and follow-up (standard therapy) phases. Rates of change in edema (measured using leg volume) were evaluated during the intervention phase. A custom-designed questionnaire was used to assess patients' satisfaction with their treatment and confidence that its effects on their health were good. RESULTS: Eight patients were included in the study. The wound surface area increased during the preliminary phase by a mean of 10 cm2/wk and decreased during the intervention phase by a mean of 4.9 cm 2/wk. Patients' mean leg volume decreased during the intervention phase. Six patients were "very satisfied" with their treatment. CONCLUSION: The adjunctive OMT protocol may have reduced edema and reversed the trend of wound growth in patients with venous stasis ulcers. Edema reduction is a mainstay of current wound therapy, and any modality that decreases edema may subsequently decrease healing times.

Crowdsourcing consensus: proposal of a novel method for assessing accuracy in echocardiography interpretation.

Quality in stress echocardiography interpretation is often gauged against coronary angiography (CA) data but anatomic obstructive coronary disease on CA is an imperfect gold standard for a stress induced wall motion abnormality. We examined the utility of crowd-sourcing a "majority-vote" consensus as an alternative 'gold standard' against which to evaluate the accuracy of an individual echocardiographer's interpretation of stress echocardiography studies. Participants independently interpreted baseline and post-exercise stress echocardiographic images of cases that had undergone follow up CA within 3 months of the stress echo in two surveys, 2 years apart. We examined the agreement of consensus on survey (survey participant response (> 60%) for one decision) with the stress echocardiography clinical read and with CA results. In the first survey, 29 participants reviewed and independently interpreted 14 stress echo cases. Consensus was reached in all 14 cases. There was good agreement between clinical and consensus (kappa = 0.57), survey participant response and consensus (kappa = 0.68) and consensus and CA results (kappa = 0.40). In the validation survey, the agreement between clinical reads and consensus (kappa = 0.75) and survey participant response and consensus (kappa = 0.81) remained excellent. Independent consensus is achievable and offers a fair comparison for stress echocardiographic interpretation. Future validation work, in other laboratories, and against hard outcomes, is necessary to test the feasibility and effectiveness of this approach.

Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography Laboratory: Improving Care for Patients With Aortic Stenosis.

BACKGROUND: The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. METHODS AND RESULTS: The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography-catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). CONCLUSIONS: A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies.