Background Clinically used general anesthetics, alone or in combination, are damaging to the developing mammalian brain. In addition to causing widespread apoptotic neurodegeneration in vulnerable brain regions, exposure to general anesthesia at the peak of synaptogenesis causes learning and memory deficiencies later in life. Our in-vivo rodent studies have suggested that activation of the intrinsic (mitochondria-dependent) apoptotic pathway is the earliest warning sign of neuronal damage, suggesting that a disturbance in mitochondrial integrity and function could be the earliest triggering events. Methods Since proper and timely mitochondrial morphogenesis is critical for brain development, we examined the long-term effects of a commonly used anesthesia combination (isoflurane, nitrous oxide, and midazolam) on the regional distribution, ultrastructural properties, and electron transport chain function of mitochondria, as well as synaptic neurotransmission, in the subiculum of rat pups. Results This anesthesia, administered at the peak of synaptogenesis, causes protracted injury to mitochondria, including significant enlargement of mitochondria (over 30%, p < 0.05), impairment of their structural integrity, about 28% increase in their complex IV activity (p < 0.05) and two-fold decrease in their regional distribution in presynaptic neuronal profiles (p < 0.05) where their presence is crucially important for the normal development and functioning of synapses. Consequently, we showed that impaired mitochondrial morphogenesis is accompanied by heightened autophagic activity, decrease in mitochondrial density (about 27%, p < 0.05) and long-lasting disturbances in inhibitory synaptic neurotransmission. The interrelation of these phenomena remains to be established. Conclusion Developing mitochondria are exquisitely vulnerable to general anesthesia and may be important early target of anesthesia-induced developmental neurodegeneration.

Patients with CS and ICDs are at high risk for ventricular arrhythmias. This population also has high rates of inappropriate shocks and device complications.

A multicenter registry for the purpose of research collaboration of this rare disease was established, with the University of Michigan serving as the coordinating center for this study. This registry was © 2014 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-The purpose of this study was to assess whether delayed enhancement (DE) on MRI is associated with ventricular tachycardia (VT)/ventricular fibrillation or death in patients with cardiac sarcoidosis and left ventricular ejection fraction >35%. Methods and Results-Fifty-one patients with cardiac sarcoidosis and left ventricular ejection fraction >35% underwent DE-MRI. DE was assessed by visual scoring and quantified with the full-width at half-maximum method. The patients were followed for 48.0±20.2 months. Twenty-two of 51 patients (63%) had DE. Forty patients had no prior history of VT (primary prevention cohort). Among those, 3 patients developed VT and 2 patients died. DE was associated with risk of VT/ventricular fibrillation or death (P=0.0032 for any DE and P<0.0001 for right ventricular DE). The positive predictive values of the presence of any DE, multifocal DE, and right ventricular DE for death or VT/ventricular fibrillation at mean follow-up of 48 months were 22%, 48%, and 100%, respectively. Among the 11 patients with a history of VT before the MRI, 10 patients had subsequent VTs, 1 of whom died. approved by all institutional review boards with data use agreements in place. Using previously published criteria, 5,6 patients who met diagnostic criteria for CS were identified. Patients from the University of Michigan, Henry Ford Hospital, University of Colorado, Johns Hopkins University, and Virginia Commonwealth University were included. Medical records were reviewed to identify patients who had cardiac MRIs, a left ventricular (LV) ejection fraction >35%, and ≥6 months of follow-up. Stored electrograms documenting arrhythmia episodes were reviewed to confirm appropriateness of ICD therapies (antitachycardia pacing or ICD discharge). Electrocardiograms and stored electrograms were analyzed, and ventricular arrhythmias were classified as monomorphic ventricular tachycardia (VT), polymorphic VT, or ventricular fibrillation (VF). Ventricular arrhythmia in the non-ICD group was defined as cardiac arrest, VT lasting ≥30 seconds or requiring defibrillation. VT/VF storm was defined as ≥3 episodes of VT/VF in a 24-hour period. Conclusions-RV DE in patients with cardiac sarcoidosis is associated with a risk of adverse events in patients with Cardiac MRIAll patients underwent cardiac MRI, including cine imaging of cardiac morphology and function and DE-MRI. All studies were performed on 1.5 Tesla scanners (Signa Excite CV/i; General Electric; Milwaukee, Wisconsin; Magnetom Sonata; Siemens Medical Solutions; Erlangen, Germany, Philips Healthcare, Best, The Netherlands). Cine imaging was performed in ventricular short-and long-axis planes using a segmented 2D steady-statefree-precession pulse sequence (repetition time,...

Background: The purpose of this 2-part study is to determine opioid prescribing patterns and characterize actual opioid use and postoperative pain control in children following discharge after closed reduction and percutaneous pinning of a supracondylar humerus fracture. Methods: A retrospective study was conducted from 2014 to 2016 to determine pain medication prescribing patterns at a single level 1 trauma center. Next, a prospective, observational study was conducted from 2017 to 2018 to determine actual pain medication use and pain scores in the acute postoperative period. Data were collected through telephone surveys performed on postoperative day 1, 3, and 5. Pain scores were collected using a parental proxy numerical rating scale (0 to 10) and opioid use was recorded as the number of doses taken. Results: From 2014 to 2016, there were 126 patients who were prescribed a mean of 47 doses of opioid medication at discharge. From 2017 to 2018, telephone questionnaires were completed in 63 patients. There was no significant difference (P>0.05) in pain ratings or opioid use by fracture type (Gartland), age, or sex. Children required a mean of 4 doses of oxycodone postoperatively. There were 18 (28%) patients who did not require any oxycodone. On average, pain scores were highest on postoperative day 1 (average 5/10) and decreased to clinically unimportant levels (<1) by postoperative day 5. Acetaminophen and ibuprofen were utilized as first-line pain medications in only 25% and 9% of patients, respectively. Two of 3 patients who used >15 oxycodone doses experienced a minor postoperative complication. Conclusions: Pediatric patients have been overprescribed opioids after operative treatment of supracondylar humerus fractures at our institution. Families who report pain scores >5 of 10 and/or persistent opioid use beyond postoperative day 5 warrant further clinical evaluation. Two of 3 pain outliers in this study experienced a minor postoperative complication. With appropriate parental counseling, satisfactory pain control can likely be achieved with acetaminophen and ibuprofen for most patients. If oxycodone is prescribed for breakthrough pain, then the authors recommend limiting to <6 doses. Level of Evidence: Level IV—observational, cohort study.