Syringe Administration of Epinephrine by Emergency Medical Technicians for Anaphylaxis

Objective: In recent years, the costs of epinephrine autoinjectors (EAIs) in the United States have risen substantially. King County Emergency Medical Services implemented the “Check and Inject” program to replace EAIs by teaching emergency medical technicians (EMTs) to manually aspirate epinephrine from a single-use 1 mg/mL epinephrine vial using a needle and syringe followed by prehospital intramuscular administration of the correct adult or pediatric dose of epinephrine for anaphylaxis or serious allergic reaction. Treatment was guided by an EMT protocol that required a trigger and symptoms. We sought to determine if the “Check and Inject” program was safely implemented by EMTs treating presumed prehospital anaphylaxis or serious allergic reaction. Methods: We conducted a prospective investigation of all cases treated as part of the “Check and Inject” program from July 2014 through December 2016 in suburban King County, Washington, and January 2016 through December 2016 within the city of Seattle. All cases were prospectively collected using a custom quality improvement data form completed by the first responding EMTs. Two physicians completed a structured review of each EMS medical record to determine if the EMTs followed the Check and Inject protocol and determine if epinephrine was clinically-indicated based on physician review. Results: Of the 411 cases eligible for analysis, EMTs followed the protocol appropriately in 367 (89.3%) cases. In the remaining 44 (10.7%) cases, the EMS incident report form failed to document either a clear inciting allergic trigger or an appropriate symptom from the protocol list. Physician review determined that epinephrine was clinically indicated in 36 of the 44 cases. Among the remaining 8 cases (1.9%) that did not meet protocol criteria and were not clinically-indicated based on physician review, none had a documented adverse reaction to the epinephrine. Conclusion: We observed that EMTs successfully implemented the manual “Check and Inject” program for severe allergic reactions and anaphylaxis in a manner that typically agreed with physician review and without any overt identified safety issues.     

Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer

PURPOSEImage-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging–derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy.Methods and MaterialsThirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge.ResultsThe measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10^?3 mm²/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10^?3 mm²/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours.ConclusionMRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.     

Connexin 43 in astrocytes contributes to motor neuron toxicity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of motor neurons in the CNS. Astrocytes play a critical role in disease progression of ALS. Astrocytes are interconnected through a family of gap junction proteins known as connexins (Cx). Cx43 is a major astrocyte connexin conducting crucial homeostatic functions in the CNS. Under pathological conditions, connexin expression and functions are altered. Here we report that an abnormal increase in Cx43 expression serves as one of the mechanisms for astrocyte‐mediated toxicity in ALS. We observed a progressive increase in Cx43 expression in the SOD1^G93A mouse model of ALS during the disease course. Notably, this increase in Cx43 was also detected in the motor cortex and spinal cord of ALS patients. Astrocytes isolated from SOD1^G93A mice as well as human induced pluripotent stem cell (iPSC)‐derived astrocytes showed an increase in Cx43 protein, which was found to be an endogenous phenomenon independent of neuronal co‐culture. Increased Cx43 expression led to important functional consequences when tested in SOD1^G93A astrocytes when compared to control astrocytes over‐expressing wild‐type SOD1 (SOD1^WT). We observed SOD1^G93A astrocytes exhibited enhanced gap junction coupling, increased hemichannel‐mediated activity, and elevated intracellular calcium levels. Finally, we tested the impact of increased expression of Cx43 on MN survival and observed that use of both a pan Cx43 blocker and Cx43 hemichannel blocker conferred neuroprotection to MNs cultured with SOD1^G93A astrocytes. These novel findings show a previously unrecognized role of Cx43 in ALS‐related motor neuron loss. GLIA 2016;64:1154–1169     

Serum calcium values in term and late-preterm neonates receiving gentamicin

Since noting an apparent increase in hypocalcemia in neonates receiving gentamicin every 24 h (q 24 h) for ≥ 4 days, we have prospectively monitored serum calcium (Ca) values in these patients receiving prolonged gentamicin therapy. This study is a retrospective analysis of those values measured during gentamicin treatment. The study included neonates with gestational age ≥ 35 weeks who received ≥ 4 days of gentamicin therapy and in whom at least one serum Ca value was measured ≥ 47 h after initiation of therapy. Hypocalcemia was defined as a serum Ca level < 8 mg/dl (2 mmol/l). Data were analyzed by Student t-test, chi-square test, and Pearson product moment correlation. There were 1,624 neonates that met the study criteria. Ca was < 8 mg/dl in 241 (15%). Ca < 8 mg/dl was more likely in boys than in girls (16.4% vs 11.8%, P = 0.01) and in neonates < 37 weeks gestational age (GA) than in those ≥ 37 weeks GA (23.9% vs 14.1%, P = 0.01). A second Ca value was obtained in 883 neonates (54%); 23.2% of neonates with initial Ca < 8 mg/dl remained hypocalcemic, and 30% of these were receiving oral Ca supplementation. The second Ca value was < 8 mg/dl in eight neonates in whom initial Ca was ≥ 8 mg/dl. Hypocalcemia is not uncommon in neonates receiving gentamicin therapy, and it may occur more frequently in boys and late-preterm infants. These data suggest that the monitoring of serum Ca levels should be considered when gentamicin is given ≥ 4 days. Presented in part at the Annual Meeting of the Pediatric Academic Societies, May 2006, San Francisco.     

High expression of p63 combined with a large N/C ratio defines a subset of human limbal epithelial cells: implications on epithelial stem cells

PURPOSE: To characterize human limbal epithelial cells based on the expression levels of nuclear protein p63 and the nucleus-to-cytoplasm (N/C) ratio. METHODS: Limbal, peripheral, and central corneal epithelia were separated from the stroma by Dispase II and subsequently were treated with trypsin to obtain single-cell suspensions. Cytospin smears of the cell suspensions were double immunostained for p63 and then stained for any one of the markers (acidic cytokeratins [AE1], K5, K3, or connexin 43 [Cx43]). They were counterstained with propidium iodide. More than 100 cells from each zone were analyzed for p63 expression levels and nuclear/cellular area using quantitative confocal microscopy. RESULTS: A gradient of p63-positive cells was observed in corneal and limbal epithelial cells. The percentage of p63-positive cells and the level of p63 expression were significantly higher in the limbal than in the peripheral or central corneal epithelium. Two-parameter (p63 levels and N/C ratio) analysis revealed the presence of a distinct population of small cells with higher levels of p63 and a large N/C ratio in the limbal epithelium. Such limbal epithelial cells were positive for AE1 and K5 but negative for K3 and Cx43. CONCLUSIONS: These results suggest that this distinct group of small cells in the limbal epithelium with greater N/C ratio, expressing high levels of nuclear protein p63, probably represent corneal epithelial stem cells.     

Phenytoin,Levetiracetam, and Pregabalin in the Acute Management of Refractory Status Epilepticus in Patients with Brain Tumors

Background  

There were nearly 700,000 patients in the United States in 2010 living with brain tumor diagnoses. The incidence of seizures in this population is as high as 70% and is historically difficult to control. Approximately 30–40% of brain tumors patients who present with status epilepticus (SE) will not respond to typical therapy consisting of benzodiazepines and phenytoin (PHT), resulting in patients with refractory status epilepticus (RSE). RSE is usually treated with anesthetic doses of propofol or midazolam infusions. This therapy can have significant risk, particularly in patients with cancer.