Adenosine Signaling and Clathrin-Mediated Endocytosis of Glutamate AMPA Receptors in Delayed Hypoxic Injury in Rat Hippocampus: Role of Casein Kinase 2.

Chronic adenosine A1R stimulation in hypoxia leads to persistent hippocampal synaptic depression, while unopposed adenosine A2AR receptor stimulation during hypoxia/reperfusion triggers adenosine-induced post-hypoxia synaptic potentiation (APSP) and increased neuronal death. Still, the mechanisms responsible for this adenosine-mediated neuronal damage following hypoxia need to be fully elucidated. We tested the hypothesis that A1R and A2AR regulation by protein kinase casein kinase 2 (CK2) and clathrin-dependent endocytosis of AMPARs both contribute to APSPs and neuronal damage. The APSPs following a 20-min hypoxia recorded from CA1 layer of rat hippocampal slices were abolished by A1R and A2AR antagonists and by broad-spectrum AMPAR antagonists. The inhibitor of GluA2 clathrin-mediated endocytosis Tat-GluA2-3Y peptide and the dynamin-dependent endocytosis inhibitor dynasore both significantly inhibited APSPs. The CK2 antagonist DRB also inhibited APSPs and, like hypoxic treatment, caused opposite regulation of A1R and A2AR surface expression. APSPs were abolished when calcium-permeable AMPAR (CP-AMPAR) antagonist (IEM or philanthotoxin) or non-competitive AMPAR antagonist perampanel was applied 5 min after hypoxia. In contrast, perampanel, but not CP-AMPAR antagonists, abolished APSPs when applied during hypoxia/reperfusion. To test for neuronal viability after hypoxia, propidium iodide staining revealed significant neuroprotection of hippocampal CA1 pyramidal neurons when pretreated with Tat-GluA2-3Y peptide, CK2 inhibitors, dynamin inhibitor, CP-AMPAR antagonists (applied 5 min after hypoxia), and perampanel (either at 5 min hypoxia onset or during APSP). These results suggest that the A1R-CK2-A2AR signaling pathway in hypoxia/reperfusion injury model mediates increased hippocampal synaptic transmission and neuronal damage via calcium-permeable AMPARs that can be targeted by perampanel for neuroprotective stroke therapy.

To Pack or Not to Pack: Inpatient Management of Epistaxis in the Elderly.

BACKGROUND: Epistaxis is common in elderly patients, occasionally necessitating hospitalization for the management of severe bleeds. In this study, we aim to explore the impact of nasal packing versus nonpacking interventions (cauterization, embolization, and ligation) on outcomes and complications of epistaxis hospitalization in the elderly. METHODS: The 2008-2013 National Inpatient Sample was queried for elderly patients (≥65 years) with a primary diagnosis of epistaxis and accompanying procedure codes for anterior and posterior nasal packing or nonpacking interventions. RESULTS: A total of 8449 cases met the inclusion criteria, with 62.4% receiving only nasal packing and 37.6% receiving nonpacking interventions. On average, nonpacking interventions were associated with a 9.9% increase in length of stay and a 54.0% increase in hospital charges. Comorbidity rates did not vary between cohorts, except for diabetes mellitus, which was less common in the nonpacking cohort (26.6% vs 29.0%; P = .014). Nonpacking interventions were associated with an increased rate of blood transfusion (24.5% vs. 21.8%; P = .004), but no significant differences in rates of stroke, blindness, aspiration pneumonia, infectious pneumonia, thromboembolism, urinary/renal complications, pulmonary complications, cardiac complications, or in-hospital mortality. Comparing patients receiving ligation or embolization, no differences in length of stay, complications, or in-hospital mortality were found; however, embolization patients incurred 232.1% greater hospital charges ( P < .001). CONCLUSION: Nonpacking interventions in the elderly do not appear to be associated with increased morbidity or mortality when compared to nasal packing only but appear to be associated with increased hospital charges and length of stay. Embolization in the elderly results in greater hospital charges but no change in outcome when compared to ligation.

Impact of obstructive sleep apnea in transsphenoidal pituitary surgery: An analysis of inpatient data.

OBJECTIVES/HYPOTHESIS: Although previous studies have reported increased perioperative complications among obstructive sleep apnea (OSA) patients undergoing any surgery requiring general anesthesia, there is a paucity of literature addressing the impact of OSA on postoperative transsphenoidal surgery (TSS) complications. The aim of this study was to analyze postoperative outcomes in transsphenoidal pituitary surgery patients with OSA. Secondarily, we examined patient characteristics and comorbidities. STUDY DESIGN: Retrospective analysis. METHODS: The 2002 to 2013 National Inpatient Sample was queried for patients undergoing TSS for pituitary neoplasm. Patients with an additional diagnosis of OSA were identified, and compared to a non-OSA cohort. RESULTS: There were 17,777 patients identified; 5.0% (N = 889) had an additional diagnosis of OSA. The OSA cohort had more comorbidities including diabetes mellitus, congestive heart failure, chronic pulmonary disease, coagulopathy, hypertension, hypothyroidism, liver disease, obesity, peripheral vascular disease, renal failure, acromegaly, and Cushing's syndrome. Postoperatively, OSA was independently associated with increased risks of tracheostomy (P = .015) and hypoxemia (P < .001), and decreased risk of cardiac complications (P = .034). OSA patients did not have increased rates of cerebrospinal fluid rhinorrhea, diabetes insipidus, reintubation, aspiration pneumonia, infectious pneumonia, thromboembolic complications, or urinary/renal complications. In-hospital mortality rates did not vary between the two cohorts. CONCLUSIONS: In patients who underwent transsphenoidal pituitary surgery, OSA was associated with higher rates of certain pulmonary and airway complications. OSA was not associated with increased non-pulmonary/airway complications or inpatient mortality, despite older average age and higher comorbidity rates. LEVEL OF EVIDENCE: 2C. Laryngoscope, 128:1027-1032, 2018.

Impact of liver disease on outcomes of patients hospitalized for epistaxis.

OBJECTIVES: Liver disease (LD) often results in coagulation abnormalities that may predispose to more severe epistaxis. The purpose of this analysis was to examine characteristics of patients hospitalized for epistaxis with LD and explore the impact of LD on patient outcomes. METHODS: The 2002 to 2013 National Inpatient Sample was queried for cases with a primary diagnosis of epistaxis. Cases with additional codes meeting the Agency for Healthcare Research and Quality's definition of LD were identified and compared to the non-LD cohort. RESULTS: Out of 39,879 cases meeting inclusion criteria, 3.6% had LD. LD was associated with younger age (55.7 years vs. 67.5 years; P < 0.001), longer hospital stay (3.9 days vs. 3.2 days; P < 0.001), and greater hospital charges ($26,141 vs. $18,200; P < 0.001) compared to the non-LD cohort. LD patients had higher rates of alcohol abuse, coagulopathy, chronic blood loss anemia, and renal failure. LD patients also had higher rates of sepsis, urinary/renal complications, respiratory failure, and infectious pneumonia. LD was associated with decreased rates of aggressive management (defined as ligation or embolization) (6.6%-9.0%; P < 0.002) and anterior or posterior nasal packing. In our multivariate logistic regression model correcting for age, gender, race, and significant comorbidities, LD was associated with 1.520 (1.336-1.729; P < 0.001) greater odds of transfusion and 2.264 (1.372-3.736; P = 0.001) greater odds of in-hospital mortality. CONCLUSION: Among patients hospitalized for epistaxis, LD resulted in greater morbidity and mortality. Clinicians should be aware of the particular risk that LD bears on the hospitalized epistaxis patient. LEVEL OF EVIDENCE: 2C. Laryngoscope, 127:2691-2697, 2017.

Smartphone use in neurosurgery? APP-solutely!

BACKGROUND: A number of smartphone medical apps have recently emerged that may be helpful for the neurosurgical patient, practitioner, and trainee. This study aims to review the current neurosurgery-focused apps available for the iPhone, iPad, and Android platforms as of December 2013. METHODS: Two of the most popular smartphone app stores (Apple Store and Android Google Play Store) were surveyed for neurosurgery-focused apps in December 2013. Search results were categorized based on their description page. Data were collected on price, rating, app release date, target audience, and medical professional involvement in app design. A review of the top apps in each category was performed. RESULTS: The search resulted in 111 unique apps, divided into these 7 categories: 16 (14%) clinical tools, 17 (15%) conference adjunct, 27 (24%) education, 18 (16%) literature, 15 (14%) marketing, 10 (9%) patient information, and 8 (7%) reference. The average cost of paid apps was $23.06 (range: $0.99-89.99). Out of the 111 apps, 71 (64%) were free, 48 (43%) had reviews, and 14 (13%) had more than 10 reviews. Seventy-three (66%) apps showed evidence of medical professional involvement. The number of apps being released every year has been increasing since 2009. CONCLUSIONS: There are a number of neurosurgery-themed apps available to all audiences. There was a lack of patient information apps for nonspinal procedures. Most apps did not have enough reviews to evaluate their quality. There was also a lack of oversight to validate the accuracy of medical information provided in these apps.