Against autonomy: How proposed solutions to the problems of living wills forgot its underlying principle.

Significant criticisms have been raised regarding the ethical and psychological basis of living wills. Various solutions to address these criticisms have been advanced, such as the use of surrogate decision makers alone or data science-driven algorithms. These proposals share a fundamental weakness: they focus on resolving the problems of living wills, and, in the process, lose sight of the underlying ethical principle of advance care planning, autonomy. By suggesting that the same sweeping solutions, without opportunities for choice, be applied to all, individual patients are treated as population-level groups-as a theoretical patient who represents a population, not the specific patient crafting his or her individualized future care plans. Instead, advance care planning can be improved through a multimodal approach that both mitigates cognitive biases and allows for customization of the decision-making process by allowing for the incorporation of a variety of methods of advance care planning.

Comparison of fluoroscopic techniques for assessment of femoral rotational alignment.

OBJECTIVES: Anatomic rotational reduction of diaphyseal femur fractures is essential in restoring limb mechanics. Errors in reproducing anteroposterior (AP) or lateral knee reference radiographs of the contralateral limb could result in inaccuracies during rotational reduction. The objective of this study was to examine whether fluoroscopic rotational variation can be observed with the same degree of precision with AP and lateral distal femur projections. METHODS: AP and lateral radiographs were obtained from intact knees of 7 cadaveric specimens using fluoroscopy. The lateral condylar width and coronal femoral width from the AP images and the posterior condylar offset and sagittal femoral width from the lateral images were measured by 3 reviewers. Interclass correlation coefficients (ICCs) among the 3 reviewers were calculated. The mean data from all reviewers were plotted against angle of rotation, and the slope (M) and regression of the line were then determined. RESULTS: ICCs were 0.997 (lateral) and 0.994 (AP), demonstrating excellent interobserver agreement. The mean (±SD) M value for lateral images was 0.016 ±â€Š0.001 and for AP images was 0.009 ±â€Š0.001 (P < .0001). The higher lateral M value represents a more appreciable difference in size of the measured segment for the same rotational change. CONCLUSIONS: The observed rotational change was 1.76 times greater on lateral images compared to AP images; thus, the lateral images may be more precise as a reference for rotation. The routine use of lateral knee radiographs to guide intraoperative rotational alignment of the femur may therefore be justified.

Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction.

OBJECTIVE: Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. No drug to date targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a JAK inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and the associated vascular pathology remains to be characterized. METHODS: MRL/lpr lupus-prone mice were administered tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum levels of autoantibodies and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular traps (NETs) release, endothelium-dependent vasorelaxation, and endothelial differentiation were compared in treated and untreated mice. RESULTS: Treatment with tofacitinib led to significant improvement in measures of disease activity, including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of proinflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated the formation of NETs and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective in both preventive and therapeutic strategies. CONCLUSION: Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus, and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage.