Heme Oxygenase-1 Regulates Myeloid Cell Trafficking in AKI

Renal ischemia-reperfusion injury is mediated by a complex cascade of events, including the immune response, that occur secondary to injury to renal epithelial cells. We tested the hypothesis that heme oxygenase-1 (HO-1) expression, which is protective in ischemia-reperfusion injury, regulates trafficking of myeloid-derived immune cells in the kidney. Age-matched male wild-type (HO-1^+/+), HO-1–knockout (HO-1^−/−), and humanized HO-1–overexpressing (HBAC) mice underwent bilateral renal ischemia for 10 minutes. Ischemia-reperfusion injury resulted in significantly worse renal structure and function and increased mortality in HO-1^−/− mice. In addition, there were more macrophages (CD45⁺ CD11b^hiF4/80^lo) and neutrophils (CD45⁺ CD11b^hi MHCII⁻ Gr-1^hi) in HO-1^−/− kidneys than in sham and HO-1^+/+ control kidneys subjected to ischemia-reperfusion. However, ischemic injury resulted in a significant decrease in the intrarenal resident dendritic cell (DC; CD45⁺MHCII⁺CD11b^loF4/80^hi) population in HO-1^−/− kidneys compared with controls. Syngeneic transplant experiments utilizing green fluorescent protein–positive HO-1^+/+ or HO-1^−/− donor kidneys and green fluorescent protein–negative HO-1^+/+ recipients confirmed increased migration of the resident DC population from HO-1^−/− donor kidneys, compared to HO-1^+/+ donor kidneys, to the peripheral lymphoid organs. This effect on renal DC migration was corroborated in myeloid-specific HO-1^−/− mice subjected to bilateral ischemia. These mice also displayed impaired renal recovery and increased fibrosis at day 7 after injury. These results highlight an important role for HO-1 in orchestrating the trafficking of myeloid cells in AKI, which may represent a key pathway for therapeutic intervention.     

The Future of Polycystic Kidney Disease Research—As Seen By the 12 Kaplan Awardees

Polycystic kidney disease (PKD) is one of the most common life-threatening genetic diseases. Jared J. Grantham, M.D., has done more than any other individual to promote PKD research around the world. However, despite decades of investigation there is still no approved therapy for PKD in the United States. In May 2014, the University of Kansas Medical Center hosted a symposium in Kansas City honoring the occasion of Dr. Grantham''s retirement and invited all the awardees of the Lillian Jean Kaplan International Prize for Advancement in the Understanding of Polycystic Kidney Disease to participate in a forward-thinking and interactive forum focused on future directions and innovations in PKD research. This article summarizes the contributions of the 12 Kaplan awardees and their vision for the future of PKD research.     

Vocational Rehabilitation in Spinal Cord Injury: What Vocational Service Activities Are Associated with Employment Program Outcome?

Background:

Designing effective vocational programs for persons with spinal cord injury (SCI) is essential for improving return to work outcome following injury. The relationship between specific vocational services and positive employment outcome has not been empirically studied.

Objective:

To examine the association of specific vocational service activities as predictors of employment.

Method:

Secondary analysis of a randomized, controlled trial of evidence-based supported employment (EBSE) with 12-month follow-up data among 81 Veteran participants with SCI.

Results:

Primary activities recorded were vocational counseling (23.9%) and vocational case management (23.8%). As expected, job development and employment supports were the most time-consuming activities per appointment. Though the amount of time spent in weekly appointments did not differ by employment outcome, participants obtaining competitive employment averaged significantly more individual activities per appointment. Further, for these participants, job development or placement and employment follow-along or supports were more likely to occur and vocational counseling was less likely to occur. Community-based employment services, including job development or placement and employment follow-along or supports as part of a supported employment model, were associated with competitive employment outcomes. Office-based vocational counseling services, which are common to general models of vocational rehabilitation, were associated with a lack of employment.

Conclusions:

Vocational services that actively engage Veterans with SCI in job seeking and acquisition and that provide on-the-job support are more likely to lead to employment than general vocational counseling that involves only job preparation.     

Achieving the optimal epinephrine effect in wide awake hand surgery using local anesthesia without a tourniquet

Background

In our experience, for all surgeries in the hand, the optimal epinephrine effect from local anesthesia—producing maximal vasoconstriction and visualization—is achieved by waiting significantly longer than the traditionally quoted 7 min from the time of injection.

Methods

In this prospective comparative study, healthy patients undergoing unilateral carpal tunnel surgery waited either 7 min or roughly 30 min, between the time of injection of 1 % lidocaine with 1:100,000 epinephrine and the time of incision. A standardized incision was made through dermis and into the subcutaneous tissue followed by exactly 60 s of measuring the quantity of blood loss using sterile micropipettes.

Results

There was a statistically significant reduction in the mean quantity of bleeding in the group that waited roughly 30 min after injection and before incision compared to the group that waited only 7 min (95 % confidence intervals of 0.06 + −0.03 ml/cm of incision, compared to 0.17 + −0.08 ml/cm, respectively) (P = 0.03).

Conclusions

Waiting roughly 30 min after injection of local anesthesia with epinephrine as oppose to the traditionally taught 7 min, achieves an optimal epinephrine effect and vasoconstriction. In the hand, this will result in roughly a threefold reduction in bleeding—making wide awake local anesthesia without tourniquet (WALANT) possible. This knowledge has allowed our team to expand the hand procedures that we can offer using WALANT. The benefits of WALANT hand surgery include reduced cost and waste, improved patient safety, and the ability to perform active intraoperative movement examinations.     

The Kaiser Permanente Shoulder Arthroplasty Registry: Results from 6,336 primary shoulder arthroplasties

Background and purpose

Shoulder arthroplasty is being performed in the United States with increasing frequency. We describe the medium-term findings from a large integrated healthcare system shoulder arthroplasty registry.

Patients and methods

Shoulder arthroplasty cases registered between January 2005 and June 2013 were included for analysis. The registry included patient characteristics, surgical information, implant data, attrition, and patient outcomes such as surgical site infections, venous thromboembolism, and revision procedures.

Results

During the study period, 6,336 primary cases were registered. Median follow-up time for all primaries was 3.3 years; 461 cases were lost to follow-up by ending of health plan membership. Primary cases were predominantly female (56%) and white (81%), with an average age of 70 years. The most common reason for surgery was osteoarthritis in 60% of cases, followed by acute fracture (17%) and rotator cuff tear arthropathy (15%). In elective shoulder arthroplasty procedures, 200 all-cause revisions (4%) were reported, with glenoid wear being the most common reason.

Interpretation

Most arthroplasties were elective procedures: over half performed for osteoarthritis. Glenoid wear was the most common reason for revision of primary shoulder arthroplasty in elective cases.In the period 2000 through 2010, over 200,000 shoulder arthroplasties were performed in the USA for osteoarthritis (Trofa et al. 2014). With the increasing use of shoulder arthroplasty (SA) over the past decade (Kim et al. 2011) and projections that future growth rates of SA may exceed those of hip and knee arthroplasty (Day et al. 2010), the need to track the outcomes of SA is becoming increasingly important.Arthroplasty registries provide an important mechanism for tracking surgical outcomes. In the fields of total hip arthroplasty and total knee arthroplasty, registries have demonstrated their importance in monitoring revisions, complications, and mortality, identifying outlier prostheses, and improving quality of care (Graves et al. 2004, Herberts and Malchau 2000, de Steiger et al. 2013, Paxton et al. 2010). SA registries have also provided critical information about demographics, survival, and outlier implants, though there have been considerably fewer publications from the younger national SA registries than from the more established hip and knee registries (Clitherow et al. 2014, Young et al. 2013, Rasmussen et al. 2012a, Rasmussen et al. 2014a and b, Fevang et al. 2009, Fevang et al. 2013). The lack of a national US registry emphasizes the need to use existing US registries to conduct international comparisons of SA patients, implants, surgical techniques, and outcomes. We present the medium-term findings of a large integrated healthcare system SA registry.     

Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction

OBJECTIVE: Creatine kinase (CK) is responsible for the transport of high-energy phosphates in excitable tissue and is of central importance in myocardial energy homeostasis. Significant changes in myocardial energetics have been reported in mice lacking the various CK isoenzymes. Our hypothesis was that ablation of CK isoenzymes leads to cardiac hypertrophy, impaired function, and aggravation of left ventricular remodeling post-myocardial infarction. METHODS: CK-deficient mice (CK KO) were examined by cardiac magnetic resonance imaging (MRI) to determine left ventricular volumes, ejection fraction, and mass: ten wild-type (WT), 6 mitochondrial CK KO (Mito-CK-/-), 10 cytosolic CK KO (M-CK-/-), and 10 mice with combined KO (M/Mito-CK-/-). RESULTS: While ejection fraction was similar in all groups, there was significant LV dilatation with a approximately 30% increase in LV end-diastolic volumes in Mito-CK-/- and in M/Mito-CK-/-. Compared to WT, there was a striking 73% and 64% increase of LV mass in Mito-CK-/- and in M/Mito-CK-/- mice, respectively, but no significant increase of LV mass (+33%; p=n.s.) in M-CK-/-. Furthermore, significant re-expression of beta-MHC, a marker of myocardial hypertrophy, was found in all CK-deficient hearts. LV remodeling was investigated by MRI in hearts of 7 WT and 10 M/Mito-CK-/- mice 4 weeks postmyocardial infarction (MI). Four weeks post-LAD ligation (MI size approximately 32%), WT and M/Mito-CK-/- showed a similar degree of cardiac dysfunction, dilatation, and hypertrophy. CONCLUSION: Mito-CK-/- and M/Mito-CK-/- mice show significant LV dilatation and marked LV hypertrophy, but LV remodeling post-MI is not aggravated. CK ablation leads to substantial adaptational changes in heart.