Adenosine triphosphate-sensitive potassium channel Kir subunits implicated in cardioprotection by diazoxide

BACKGROUND: ATP-sensitive potassium (K(ATP)) channel openers provide cardioprotection in multiple models. Ion flux at an unidentified mitochondrial K(ATP) channel has been proposed as the mechanism. The renal outer medullary kidney potassium channel subunit, potassium inward rectifying (Kir)1.1, has been implicated as a mitochondrial channel pore-forming subunit. We hypothesized that subunit Kir1.1 is involved in cardioprotection (maintenance of volume homeostasis and contractility) of the K(ATP) channel opener diazoxide (DZX) during stress (exposure to hyperkalemic cardioplegia [CPG]) at the myocyte and mitochondrial levels. METHODS AND RESULTS: Kir subunit inhibitor Tertiapin Q (TPN-Q) was utilized to evaluate response to stress. Mouse ventricular mitochondrial volume was measured in the following groups: isolation buffer; 200 μmol/L of ATP; 100 μmol/L of DZX+200 μmol/L of ATP; or 100 μmol/L of DZX+200 μmol/L of ATP+TPN-Q (500 or 100 nmol/L). Myocytes were exposed to Tyrode’s solution (5 minutes), test solution (Tyrode’s, cardioplegia [CPG], CPG+DZX, CPG+DZX+TPN-Q, Tyrode’s+TPN-Q, or CPG+TPN-Q), N=12 for all (10 minutes); followed by Tyrode’s (5 minutes). Volumes were compared. TPN-Q, with or without DZX, did not alter mitochondrial or myocyte volume. Stress (CPG) resulted in myocyte swelling and reduced contractility that was prevented by DZX. TPN-Q prevented the cardioprotection afforded by DZX (volume homeostasis and maintenance of contractility). CONCLUSIONS: TPN-Q inhibited myocyte cardioprotection provided by DZX during stress; however, it did not alter mitochondrial volume. Because TPN-Q inhibits Kir1.1, Kir3.1, and Kir3.4, these data support that any of these Kir subunits could be involved in the cardioprotection afforded by diazoxide. However, these data suggest that mitochondrial swelling by diazoxide does not involve Kir1.1, 3.1, or 3.4

Soft Landing technique as a possible prevention strategy for proximal junctional failure following adult spinal deformity surgery

BackgroundThis cross sectional study describes a "Soft Landing" strategy utilizing hooks for minimizing proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). The technique creates a gradual transition from a rigid segmental construct to unilateral hooks at the upper instrumented level and preservation of the soft tissue attachments on the contralateral side of the hooks. Authors devise a novel classification system for better grading of PJK severity.MethodsThirty-nine consecutive adult spinal deformity (ASD) patients at a single institution received the "Soft Landing" technique. The proximal junctional angle was measured preoperatively and at last follow-up using standing 36-inch spinal radiographs. Changes in proximal junctional angle and rates of PJK and PJF were measured and used to create a novel classification system for evaluating and categorizing ASD patients postoperatively.ResultsThe mean age of the cohort was 61.4 years, and 90% of patients were women. Average follow up was 2.2 years. The mean change in proximal junctional angle was 8° (SD 7.4°) with the majority of patients (53%) experiencing less than 10° and only 1 patients with proximal junctional angle over 20°. Four patients (10%) needed additional surgery for proximal extension of the uppermost instrumented vertebra (UIV) secondary to PJF.ConclusionsSoft Landing technique is a possibly effective treatment strategy to prevent PJK and PJF following ASD that requires further evaluation. The described classification system provides management framework for better grading of PJK. The "Soft Landing" technique warrants further comparison to other techniques currently used to prevent both PJK and failure

Impact of Myelopathy Severity and Degree of Deformity on Postoperative Outcomes in Cervical Spinal Deformity Patients

Objective Malalignment of the cervical spine can result in cord compression, leading to a myelopathy diagnosis. Whether deformity or myelopathy severity is stronger predictors of surgical outcomes is understudied. Methods Surgical cervical deformity (CD) patients with baseline (BL) and up to 1-year data were included. Modified Japanese Orthopaedic Association (mJOA) score categorized BL myelopathy (mJOA = 18 excluded), with moderate myelopathy mJOA being 12 to 17 and severe myelopathy being less than 12. BL deformity severity was categorized using the mismatch between T1 slope and cervical lordosis (TS-CL), with CL being the angle between the lower endplates of C2 and C7. Moderate deformity was TS-CL less than or equal to 25° and severe deformity was greater than 25°. Categorizations were combined into 4 groups: group 1 (G1), severe myelopathy and severe deformity; group 2 (G2), severe myelopathy and moderate deformity; group 3 (G3), moderate myelopathy and moderate deformity; group 4 (G4), moderate myelopathy and severe deformity. Univariate analyses determined whether myelopathy or deformity had greater impact on outcomes. Results One hundred twenty-eight CD patients were included (mean age, 56.5 years; 46% female; body mass index, 30.4 kg/m2) with a BL mJOA score of 12.8±2.7 and mean TS-CL of 25.9°±16.1°. G1 consisted of 11.1% of our CD population, with 21% in G2, 34.6% in G3, and 33.3% in G4. At BL, Neck Disability Index (NDI) was greatest in G2 (p=0.011). G4 had the lowest EuroQol-5D (EQ-5D) (p<0.001). Neurologic exam factors were greater in severe myelopathy (p<0.050). At 1-year, severe deformity met minimum clinically important differences (MCIDs) for NDI more than moderate deformity (p=0.002). G2 had significantly worse outcomes compared to G4 by 1-year NDI (p=0.004), EQ-5D (p=0.028), Numerical Rating Scale neck (p=0.046), and MCID for NDI (p=0.001). Conclusion Addressing severe deformity had increased clinical weight in improving patient-reported outcomes compared to addressing severe myelopathy

Predictors of Failure of Nonoperative Management Following Subaxial Spine Trauma and Creation of Modified Subaxial Injury Classification System

BACKGROUND: Subaxial cervical spine injuries may be treated with either nonoperative stabilization or surgical fixation. The subaxial injury classification (SLIC) provides 1 method for suggesting the degree of necessity for surgery. In the current study, we examined if the SLIC score, or other preoperative metrics, can predict failure of nonoperative management. METHODS: We performed a retrospective chart review to identify patients who presented with acute, nonpenetrating, subaxial cervical spine injury within our health system between 2007 and 2016. Patient demographics, medical comorbidities, injuries, and treatments were collected. Logistic regression analysis was used to determine potential predictors of failure of nonoperative management. RESULTS: During the study period, 40 patients met the inclusion criteria. A small subset of patients failed nonoperative management (n = 5, 12.5%). The mean SLIC score was 3.9 ± 1.9; however, 14 (35%) patients had scores \u3e4. Neither total SLIC score (P = 0.68) nor SLIC subscores (morphology [P = 0.96], discoligamentous complex [P = 0.83], neurologic status [P = 0.60]) predicted failure of nonoperative treatment. Time to evaluation/treatment did predict failure of nonoperative management. Evaluation within 8 hours of injury was a negative predictor of failure (odds ratio = 0.03, P = 0.001) and evaluation 24 hours or more after injury was a positive predictor of failure (odds ratio = 66.00, P \u3c 0.001). We created a modified SLIC score on the basis of these findings, which significantly predicted failure of nonoperative management (P = 0.044). CONCLUSIONS: Management of subaxial spine injuries is complex. In our cohort, SLIC scoring did not adequately predict odds of failure of nonoperative management. Time to evaluation, however, did. We created a modified SLIC score that significantly predicted failure of nonoperative management