Abstract
BACKGROUND:
Global sagittal malalignment is significantly correlated with health-related quality-of-life scores in the setting of spinal deformity. In order to address rigid deformity ...patterns, the use of spinal osteotomies has seen a substantial increase. Unfortunately, variations of established techniques and hybrid combinations of osteotomies have made comparisons of outcomes difficult.
OBJECTIVE:
To propose a classification system of anatomically-based spinal osteotomies and provide a common language among spine specialists.
METHODS:
The proposed classification system is based on 6 anatomic grades of resection (1 through 6) corresponding to the extent of bone resection and increasing degree of destabilizing potential. In addition, a surgical approach modifier is added (posterior approach or combined anterior and posterior approaches). Reliability of the classification system was evaluated by an analysis of 16 clinical cases, rated 2 times by 8 different readers, and calculation of Fleiss kappa coefficients.
RESULTS:
Intraobserver reliability was classified as “almost perfect”; Fleiss kappa coefficient averaged 0.96 (range, 0.92-1.0) for resection type and 0.90 (0.71-1.0) for the approach modifier. Results from the interobserver reliability for the classification were 0.96 for resection type and 0.88 for the approach modifier.
CONCLUSION:
This proposed anatomically based classification system provides a consistent description of the various osteotomies performed in spinal deformity correction surgery. The reliability study confirmed that the classification is simple and consistent. Further development of its use will provide a common frame for osteotomy assessment and permit comparative analysis of different treatments.
Abstract
BACKGROUND:
Global sagittal malalignment is significantly correlated with health-related quality-of-life scores in the setting of spinal deformity. In order to address rigid deformity ...patterns, the use of spinal osteotomies has seen a substantial increase. Unfortunately, variations of established techniques and hybrid combinations of osteotomies have made comparisons of outcomes difficult.
OBJECTIVE:
To propose a classification system of anatomically-based spinal osteotomies and provide a common language among spine specialists.
METHODS:
The proposed classification system is based on 6 anatomic grades of resection (1 through 6) corresponding to the extent of bone resection and increasing degree of destabilizing potential. In addition, a surgical approach modifier is added (posterior approach or combined anterior and posterior approaches). Reliability of the classification system was evaluated by an analysis of 16 clinical cases, rated 2 times by 8 different readers, and calculation of Fleiss kappa coefficients.
RESULTS:
Intraobserver reliability was classified as "almost perfect"; Fleiss kappa coefficient averaged 0.96 (range, 0.92-1.0) for resection type and 0.90 (0.71-1.0) for the approach modifier. Results from the interobserver reliability for the classification were 0.96 for resection type and 0.88 for the approach modifier.
CONCLUSION:
This proposed anatomically based classification system provides a consistent description of the various osteotomies performed in spinal deformity correction surgery. The reliability study confirmed that the classification is simple and consistent. Further development of its use will provide a common frame for osteotomy assessment and permit comparative analysis of different treatments.
Hepatocyte growth factor (HGF) is a potent inducer of motility in epithelial cells. Since we have previously found that activation of the epidermal growth factor receptor (EGFR) is an absolute ...prerequisite for induction of motility of corneal epithelial cells after wounding, we investigated whether induction of motility in response to HGF is also dependent on activation of the EGFR. We now report that HGF induces transactivation of the EGFR in an immortalized line of corneal epithelial cells, in human skin keratinocytes, and in Madin–Darby canine kidney cells. EGFR activation is unconditionally required for induction of motility in corneal epithelial cells, and for induction of a fully motile phenotype in Madin–Darby canine kidney cells. Activation of the EGFR occurs through amphiregulin and heparin-binding epidermal growth factor-like growth factor. Early after HGF stimulation, blocking EGFR activation does not inhibit extracellular-signal regulated kinase 1/2 (ERK1/2) activation by HGF, but the converse is seen after approximately 1 h, indicating the existence of EGFR-dependent and -independent routes of ERK1/2 activation. In summary, HGF induces transactivation of the EGFR in epithelial cells, and this is a prerequisite for induction of full motility.
Background The purpose of this study was to evaluate the effect of sling immobilization on driving performance with use of a driving simulator. Methods This is a prospective trial with a cohort of 21 ...healthy volunteers comparing their driving ability with and without sling immobilization on their dominant (driving) extremity. Multiple variables, including number of collisions, off-road excursions, and centerline crossings, were measured with a validated driving simulator. Trials were separated by 2 weeks to control for “adaptations” to the simulator. Statistical significance was found in collisions between sling and no-sling tests. Results The total number of collisions for trial 1 (no sling) was 36 (mean, 1.7 ± 1.2) compared with 73 (3.7 ± 1.6) ( P < .01) for trial 2 (sling immobilization). Approximately 70% of participants with upper extremity immobilization were involved in ≥3 collisions; approximately 70% of no-sling participants were involved in ≤2 collisions. There was no statistically significant difference between groups with respect to overall vehicle road position and control. Conclusion Sling immobilization of the dominant driving arm results in a decrease in driving performance and safety with respect to the number of collisions in a simulated driving circuit ( P < .01). There were no significant differences in driving parameters that are indicative of overall vehicle position and control. The decrease in driving performance with respect to the number of collisions is likely to be related to the effect the immobilized arm has on effectively performing evasive maneuvers during hazardous driving conditions.
Most formulations of artificial tears include high-molecular weight hydrophilic polymers (hydrogels) that are usually thought to serve to enhance viscosity and to act as demulcents. A few reports ...have indicated that application of some of the polymers accelerates healing of wounds in epithelia. Since activation of the epidermal growth factor (EGF) receptor is critical for spontaneous corneal epithelial wound healing, we tested commonly used hydrogels for their ability to activate the EGF receptor and enhance closure of wounds. Five structurally unrelated hydrogels used in artificial tears were found to activate the EGF receptor. Importantly, two of the hydrogels enhanced wound healing in an organ culture model. We propose that the efficacy of hydrogels in treating dry eye may be related to their ability to activate the EGF receptor, and that hydrogels are inexpensive, safe agents to promote healing of wounds in the cornea and possibly in other tissues.
Histological growth plate analysis. OBJECTIVE.: To evaluate the histological effects on vertebral growth plates following corrective mechanical tethering in the porcine scoliosis model.
...Theoretically, growth modulation allows progressive vertebral correction in the setting of scoliosis (Hueter-Volkmann principle).
This IACUC-approved study divided 9 immature Yorkshire pigs into 2 groups: deforming tether release (TR, n = 4) group and anterior corrective (AC, n = 5) tether group. Once 50° coronal Cobb was demonstrated, TR had release of the deforming tether, whereas AC had release of the deforming tether and additional placement of a corrective tether. After 20 weeks of observation, pigs were killed, spines were removed, and apical samples were prepared for histological study. Growth plate analysis included the following histological parameters: proliferative zone height, hypertrophic zone height, and cell heights within the hypertrophic zone. Student t test was used to evaluate differences within and between groups.
No significant differences were found within the release group on the concave versus convex side in terms of proliferative zone height, hypertrophic zone height, and cell heights in the hypertrophic zone. In the anterior correction group, the proliferative zone height was significantly smaller on the concave side than on the convex side (P < 0.01); no significant differences were found in AC on the concave versus convex side in terms of hypertrophic zone height and cell heights in the hypertrophic zone. No significant differences were found in any parameters between TR and AC on either the concave or the convex side.
No significant decrease in any of the measured parameters was observed in the anterior correction group compared with the tether release group. These histological findings are consistent with preservation of growth potential.
IMPORTANCE: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, ...cardiovascular events, and death. OBJECTIVE: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD. DESIGN, SETTING, AND PARTICIPANTS: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center–based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included. INTERVENTION: The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations. RESULTS: The study included 174 PCPs and 2026 patients (mean SD age, 75.3 0.3 years; 1223 60.4% female; mean SD SBP at baseline, 154.0 14.3 mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, −14.6 95% CI, −13.1 to −16.0 mm Hg vs −11.7 −10.2 to −13.1 mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% 95% CI, 46.5% to 54.3% vs 47.1% 95% CI, 43.3% to 51.0%). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% 95% CI, 45.1% to 54.8% vs 34.6% 95% CI, 29.8% to 39.4%; P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03679247
Compound LY354740 (+)-2-aminobicyclo3.1.0hexane-2,6-dicarboxylic acid, an analog of glutamic acid, is a selective group 2 metabotropic glutamate receptor agonist in clinical development for the ...treatment of anxiety. Studies have been conducted to characterize the absorption, disposition, metabolism, and excretion of LY354740 in rats and dogs after intravenous bolus or oral administration. Plasma concentrations of LY354740 were measured using a validated gas chromatography/mass spectrometry assay. In rats, LY354740 demonstrated linear pharmacokinetics after oral administration from 30 to 1000 mg/kg. The oral bioavailability of LY354740 was approximately 10% in rats and 45% in dogs. In the dog, food decreased the mean area under the plasma concentration-time curve value by approximately 34%, hence, decreasing the oral bioavailability of the compound. Excretion studies in both rats and dogs indicate that the absorbed drug is primarily eliminated via renal excretion. In addition, tissue distribution in rats showed that the highest levels of radioactivity were in the kidney and gastrointestinal tract, which is consistent with the excretion studies. Metabolism of LY354740 was evaluated in vitro using rat and dog liver microsomes and rat liver slices. In addition, urine and fecal samples from rat and dog excretion studies were profiled using HPLC with radio-detection. These evaluations indicated that neither rats nor dogs metabolized LY354740. In summary, LY354740 is poorly absorbed in rats, moderately absorbed in dogs, and rapidly excreted as unchanged drug in the urine.
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