Sodium-Glucose Cotransporter-2 Inhibitor-Related Diabetic Ketoacidosis: Accuracy Verification of Operational Definition

Background@#The most important aspect of a retrospective cohort study is the operational definition (OP) of the disease. We developed a detailed OP for the detection of sodiumglucose cotransporter-2 inhibitors (SGLT2i) related to diabetic ketoacidosis (DKA). The OP was systemically verified and analyzed. @*Methods@#All patients prescribed SGLT2i at four university hospitals were enrolled in this experiment. A DKA diagnostic algorithm was created and distributed to each hospital;subsequently, the number of SGLT2i-related DKAs was confirmed. Then, the algorithm functionality was verified through manual chart reviews by an endocrinologist using the same OP. @*Results@#A total of 8,958 patients were initially prescribed SGLT2i. According to the algorithm, 0.18% (16/8,958) were confirmed to have SGLT2i-related DKA. However, based on manual chart reviews of these 16 cases, there was only one case of SGLT2i-related DKA (positive predictive value = 6.3%). Even after repeatedly narrowing the diagnosis range of the algorithm, the effect of a positive predictive value was insignificant (6.3–10.0%, P > 0.999). @*Conclusion@#Owing to the nature of electronic medical record data, we could not create an algorithm that clearly differentiates SGLT2i-related DKA despite repeated attempts. In all retrospective studies, a portion of the samples should be randomly selected to confirm the accuracy of the OP through chart review. In retrospective cohort studies in which chart review is not possible, it will be difficult to guarantee the reliability of the results.

A review of low-intensity focused ultrasound for neuromodulation

The ability of ultrasound to be focused into a small region of interest through the intact skull within the brain has led researchers to investigate its potential therapeutic uses for functional neurosurgery and tumor ablation. Studies have used high-intensity focused ultrasound to ablate tissue in localised brain regions for movement disorders and chronic pain while sparing the overlying and surrounding tissue. More recently, low-intensity focused ultrasound (LIFU) that induces reversible biological effects has been emerged as an alternative neuromodulation modality due to its bi-modal (i.e. excitation and suppression) capability with exquisite spatial specificity and depth penetration. Many compelling evidences of LIFU-mediated neuromodulatory effects including behavioral responses, electrophysiological recordings and functional imaging data have been found in the last decades. LIFU, therefore, has the enormous potential to improve the clinical outcomes as well as to replace the currently available neuromodulation techniques such as deep brain stimulation (DBS), transcranial magnetic stimulation and transcranial current stimulation. In this paper, we aim to provide a summary of pioneering studies in the field of ultrasonic neuromodulation including its underlying mechanisms that were published in the last 60 years. In closing, some of potential clinical applications of ultrasonic brain stimulation will be discussed.

Development and Accuracy Test of a Robot-arm Type Image-guided Surgery System for Percutaneous Screw Fixation of the Sacro-iliac Joint

PURPOSE: To develop a robot-arm type image-guided surgery system for percuatneous screw fixation of the sacro-iliac joint and to evaluate its accuracy. MATERIALS AND METHODS: We have developed an image-guided surgery system using a three-dimensional digitizer (Microscribe 3-D G2, Immersion, USA) and a personal computer. The registration error and target localization error at fiducial registration were measured 30 times for each using a phantom made with plastic pelvic bone model (Sawbones, USA). Sixteen 6.5 mm cannulated screws were inserted into four plastic bone models, and the accuracy was evaluated. RESULTS: The target localization error was 1.46+/-0.47 mm while the registration error was 0.73+/-0.23 mm. All of the 16 screws were inserted well across the sacro-iliac joint, and there was neither cortical breach nor collision between screws or washers. CONCLUSION: The accuracy of the developed system was similar to that of optical tracker-based navigation systems, and its helpfulness and usefulness was proven with simulation surgery using plastic bone models.

Enhanced expression of constitutive and inducible forms of nitric oxide synthase in autoimmune encephalomyelitis

To elucidate the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we analyzed the expression of constitutive neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) in the spinal cords of rats with EAE. We further examined the structural interaction between apoptotic cells and spinal cord cells including neurons and astrocytes, which are potent cell types of nitric oxide (NO) production in the brain. Western blot analysis showed that three forms of NOS significantly increased in the spinal cords of rats at the peak stage of EAE, while small amounts of these enzymes were identified in the spinal cords of rats without EAE. Immunohistochemical study showed that the expression of either nNOS or eNOS increased in the brain cells including neurons and astrocytes during the peak and recovery stages of EAE, while the expression of iNOS was found mainly in the inflammatory macrophages in the perivascular EAE lesions. Double labeling showed that apoptotic cells had intimate contacts with either neurons or astrocytes, which are major cell types to express nNOS and eNOS constitutively. Our results suggest that the three NOS may play an important role in the recovery of EAE.