Modulation of the inflammatory response benefits treatment-resistant bipolar depression: A randomized clinical trial.

OBJECTIVE: The goal of this study was to reduce treatment resistance and enhance antidepressant response in patients with treatment-resistant bipolar depression (TRBDD) by modulating inflammatory activation. METHODS: Forty-seven TRBDD patients completed a randomized, double-blind, placebo (PBO)-controlled two-arm study using celecoxib (CBX), a cyclooxygenase 2 (COX-2) inhibitor, in combination with escitalopram (ESC). The Hamilton Depression (17-Item) and the Hamilton Anxiety Rating Scales were used to quantify symptom severity. Self-rating instruments included BDI, BAI and QLES-Q questioner. An adverse events inventory was used, and the possibility of bleeding diathesis was monitored. Complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (APTT) were determined. Comparison of mood scores between the CBX and PBO groups were conducted using a mixed ANOVA and an Independent Sample Student t-test. RESULTS: The CBX adjunctive treatment produced significantly more responders and remitters than the PBO arm. Compared to the PBO group (n = 20), the CBX group (n = 27) experienced lower depression severity through the entire course of the study, showing significant decrease in depression and anxiety scores as early as week 1. Except for initial mild nausea, no adverse events were reported and study medications were well tolerated. CONCLUSIONS: Modulation of the inflammatory response through targeted inhibition of the enzyme COX-2 by means of CBX reduces TRBDD and augments and accelerates treatment response in an efficacious and safe manner. Future studies should replicate these findings and additionally investigate whether prolonged administration of CBX is required to maintain remission by adding a discontinuation phase to the study design. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT01479829.

Upper Eyelid Approach for the Reconstruction of Isolated Fractures of the Anterior Wall of the Frontal Sinus.

The management of frontal sinus fractures can vary widely depending on involvement of the anterior wall, the posterior wall, and the frontonasal duct. The main morbidity associated with isolated anterior wall fractures is an aesthetic deformity. Treatment includes coronal, endoscopic, and transcutaneous approaches. However, each has reported limitations and associated risks of iatrogenic injuries. In this paper, the authors discuss a novel approach through the upper eyelid crease and examine 4 cases where it is utilized for anterior frontal sinus wall, superior orbital rim, and orbital roof fracture repair.

Use of two cleft lip and palate classification systems by nonsubspecialized health care providers.

Objective : The purpose of this experiment was to evaluate the use of RPL and LAHSHAL coding systems by individuals not specialized in craniofacial abnormalities to code cleft lip and palate (CLP). The effectiveness of system use by referring services and the electronic medical record (EMR) applicability of other CLP systems was evaluated by literature review and testing data. Design and Participants : The RPL and LAHSHAL systems were presented together to a sample of medical students (n = 28) and neonatal intensive care unit nurses (n = 24) from Loma Linda University. Following the presentation, a test assessing the application of each system was administered. A second assessment of the medical students (n = 23) 2 weeks after the initial presentation evaluated system retention. Scores were compared using t test (P ≤ .05). Results : Both the medical students and nurses used RPL more accurately than LAHSHAL in the first assessment (76.9% versus 45.2%, P < .001; 46.6% versus 22.5%, P < .001). Medical students again used RPL more accurately at the 2-week assessment (72.2% versus 43.7%, P < .001). Accuracy of use within each system was not significantly different between the two assessments. Conclusion : Our test results and literature review indicate that, when compared with LAHSHAL, RPL is more easily and accurately used by representatives not specialized in abnormalities in CLP; therefore, RPL may be a more effective system for nonspecialist health care providers to improve the accuracy of referrals and simple EMR documentation.

The neurosurvival factor Humanin inhibits beta-cell apoptosis via signal transducer and activator of transcription 3 activation and delays and ameliorates diabetes in nonobese diabetic mice.

Pancreatic beta-cell apoptosis is important in the pathogenesis and potential treatment of type 1 diabetes mellitus. We investigated whether Humanin, a recently described survival factor for neurons, could improve the survival of beta-cells and delay or treat diabetes in the nonobese diabetic (NOD) model. Humanin reduced apoptosis induced by serum starvation in NIT-1 cells and decreased apoptosis induced by cytokine treatment. Humanin induced signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation over a 24-hour time course. Specific inhibition of signal transducer and activator of transcription 3 resulted in nullifying the protective effect of Humanin. Humanin normalized glucose tolerance in NOD mice treated for 6 weeks, and their pancreata revealed decreased lymphocyte infiltration and severity. In addition, Humanin delayed/prevented the onset of diabetes in NOD mice treated for 20 weeks. In summary, Humanin treatment decreases cytokine-induced apoptosis in beta-cells in vitro and improved glucose tolerance and onset of diabetes in NOD mice in vivo. This indicates that Humanin may be useful for islet protection and survival in a spectrum of diabetes-related therapeutics.