Circulating Mitochondrial DNA Is Associated With High Levels of Fatigue in Two Independent Sarcoidosis Cohorts.

BACKGROUND: Patients with sarcoidosis who develop severe clinical phenotypes of pulmonary fibrosis or multiorgan disease experience debilitating symptoms, with fatigue being a common chief complaint. Studies that have investigated this patient-related outcome measure (PROM) have used the Fatigue Assessment Scale (FAS), a self-reported questionnaire that reflects mental and physical domains. Despite extensive work, its cause is unknown and treatment options remain limited. Previously, we showed that the plasma of patients with sarcoidosis with extrapulmonary disease endorsing fatigue was enriched for mitochondrial DNA (mtDNA), a ligand for the innate immune receptor toll-like receptor 9 (TLR9). Through our cross-disciplinary platform, we investigated a relationship between sarcoidosis-induced fatigue and circulating mtDNA. RESEARCH QUESTION: Is there a psychobiologic mechanism that connects sarcoidosis-induced fatigue and mtDNA-mediated TLR9 activation? STUDY DESIGN AND METHODS: Using a local cohort of patients at Yale (discovery cohort) and the National Institutes of Health-sponsored Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis study (validation cohort), we scored the FAS and quantified in the plasma, mtDNA concentrations, TLR9 activation, and cytokine levels. RESULTS: Although FAS scores were independent of corticosteroid use and Scadding stage, we observed a robust association between FAS scores, which included mental and physical domains, and multiorgan sarcoidosis. Subsequently, we identified a significant correlation between plasma mtDNA concentrations and all domains of fatigue. Additionally, we found that TLR9 activation is associated with all aspects of the FAS and partially mediates this PROM through mtDNA. Last, we found that TLR9-associated soluble mediators in the plasma are independent of all facets of fatigue. INTERPRETATION: Through our cross-disciplinary translational platform, we identified a previously unrecognized psychobiologic connection between sarcoidosis-induced fatigue and circulating mtDNA concentrations. Mechanistic work that investigates the contribution of mtDNA-mediated innate immune activation in this PROM and clinical studies with prospective cohorts has the potential to catalyze novel therapeutic strategies for this patient population and those with similar conditions.

After-Hours Calls in a Joint Replacement Practice.

BACKGROUND: Early discharge after joint arthroplasty requires additional resources to manage patients safely after surgery. Patient concerns must be addressed during nonbusiness hours to keep patients out of the emergency department and avoid readmissions. The goal of our study was to determine how type of system is utilized in a busy early discharge joint replacement practice. METHODS: In our total joint program, we have utilized a Google phone number to give patients access to a member of the surgical team after business hours and on weekends. The duration, chief complaint, and resolution of from the phone calls were collected prospectively for 3 months (July 3, 2017-October 3, 2017). RESULTS: Sixty-eight calls were received from 55 patients during the 3-month study period. Three hundred twenty-five cases were performed. The average duration of a call was 3.9 minutes. The average length of time from surgery to call was 17.5 days (range 0-442 days). Suboptimal health literacy was associated with increased calls within the first week after surgery (odds ratio = 4.1, 95% confidence interval = 1.2-14.5, P = .022). A chief complaint of pain was associated with primary versus revision surgery. (odds ratio = 3.23, 95% confidence interval = 1.08-9.86). DISCUSSION: An "after-hours" telephone contact service with a member of the surgical team may help avoid unnecessary emergency department visits. About one phone call was received per day, with an average duration of 3.9 minutes per call. These additional resources are necessary to maintain patient safety and satisfaction in early discharge joint replacement.

Choices, Compromises, and Controversies in Total Knee and Total Hip Arthroplasty Modifiable Risk Factors: What You Need to Know.

BACKGROUND: Total joint arthroplasty has historically been very successful for most patients, yet some still incur a complication. In an era of value-based care, certain efforts need to be taken to optimize patients' risk profile before surgery to decrease the chances of readmission or surgical complication. METHODS: We reviewed 10 key medical conditions and lifestyle factors that surgeons should improve before pursuing total joint arthroplasty and provide a summary of the available literature to guide certain optimization thresholds. RESULTS: With careful attention to and the creation of a preoperative checklist, surgeons can identify key domains, including morbid obesity, malnutrition, diabetes, smoking, opioid use, poor dentition, cardiovascular disease, preoperative anemia, staphylococcus colonization, and psychological disorders and intervene based on an individual's areas of deficiencies. CONCLUSION: By following stringent protocols and rescheduling surgery until optimization has occurred, we can work to provide patients the best chance for a successful outcome with an elective hip or knee arthroplasty.

IL-4 inhibition of IL-1 induced Matrix metalloproteinase-3 (MMP-3) expression in human fibroblasts involves decreased AP-1 activation via negative crosstalk involving of Jun N-terminal kinase (JNK).

Matrix metalloproteinase-3 (MMP-3) over-expression is associated with tissue destruction in the context of chronic inflammation. Previous studies showed that IL-4 inhibits induction of MMP-3 by IL-1ß, and suggested that AP-1 might be involved. Here we show that IL-1 induced binding of transcription factor AP-1 to the MMP-3 promoter consists primarily of c-Jun, JunB, and c-Fos and that binding of c-Jun and c-Fos is inhibited by the combination of cytokines while binding of Jun B is not. Mutation of the AP-1 site in the MMP-3 promoter decreased the ability of IL-4 to inhibit its transcription in transfected MG-63 cells. Western blotting showed that both cytokines activate Jun N-terminal kinase (JNK), but with somewhat different kinetics, and that activation of JNK by both cytokines individually is inhibited by the combination. These results indicate that IL-4 inhibition of MMP-3 expression is associated with reduction of IL-1 induced binding of active forms of the AP-1 dimer, while less active JunB-containing dimers remain, and suggest that these changes are associated with decreased activation of JNK.

Core competencies required for the cardiac surgical nurse practitioner.

PURPOSE: To propose a set of core competencies for the cardiac surgery nurse practitioner (CSNP). DATA SOURCES: Research, review articles, standards of practice, hospital practice guidelines. CONCLUSION: Although there have been preliminary studies that demonstrate the effectiveness and cost savings associated with the use of a CSNP, specific competencies have yet to be defined. The CSNP provides direct patient care and functions simultaneously as part of an interdisciplinary team. The CSNP cares for the patient from preadmission until postdischarge. The CSNP facilitates the transfer of information along the transitions of care that is vital to positive patient outcomes. IMPLICATIONS FOR PRACTICE: Changes in health care have forced providers to find ways to decrease the cost of services while maintaining high-quality, efficient care for their patients. In addition, there is a rising acuity of the patient population admitted for cardiac surgery. The continued development of the role of the CSNP and evidence that supports the cost savings and improved patient outcomes that result from the use of CSNPs will encourage more and more cardiac surgery programs to use CSNPs along the continuum of care.