A Preliminary Formula to Predict Timing of Symptom Resolution for Collegiate Athletes Diagnosed With Sport Concussion

ContextSymptom presentation and recovery after sport concussion (SC) are variable. Empirically based models documenting typical symptom duration would assist health care providers in managing return to play after SC.ObjectiveTo develop a prediction model for SC symptom duration.DesignCross-sectional study.SettingTwo National Collegiate Athletic Association Division I university laboratories.Intervention(s)Participants completed the Revised Head Injury Scale (HIS-r), Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT), and Sensory Organization Test within 24 hours of SC diagnosis.ResultsThe final formula consisted of the HIS-r''s self-reported neck pain, drowsiness, tingling, and nervousness duration and ImPACT total symptom severity (R = 0.62, R² = 39%, R²_adj = 34.2%, P < .001). Approximately 29% (R²_cv = 29%) of the variance associated with total days symptomatic after SC was explained by our preliminary formula when cross-validated. The current formula correctly identified 76% of participants who recovered within 10 days of injury.ConclusionsOur results suggest that self-reported duration of 4 symptoms during the initial 24 hours after injury along with total symptom severity as measured by ImPACT accounted for a considerable amount of variance associated with days symptomatic after SC in collegiate athletes. Until the formula is cross-validated in a college-aged sample, caution is warranted in using it clinically.Key Words: traumatic brain injuries, prediction, prolonged recovery, symptom severity, symptom duration

Key Points

• A formula to predict symptom resolution after sport concussion primarily consisting of initial symptom duration and severity correctly identified 76% of National Collegiate Athletic Association Division I collegiate athletes who recovered within 10 days.
• Before it can be used clinically, the formula must be cross-validated on larger samples.

The clinical presentation of and recovery from sport concussion (SC) are variable among athletes. Recovery curves based on animal models suggest the metabolic vulnerability associated with concussion resolves within approximately 7 to 10 days.^1,2 During this period of metabolic dysfunction, athletes experience neurocognitive and motor deficits as well as a constellation of symptoms.^3–5 These sequelae serve as markers that clinicians can measure to track recovery and make informed return-to-play and return-to-learn decisions.⁶The resolution of motor (eg, postural stability) and neurocognitive (eg, memory, reaction time, information-processing speed) deficits, along with self-reported symptoms (eg, headache, nausea, dizziness), varies based on a number of factors. These factors include age, sex, background history, comorbid conditions, and signs and symptoms reported or observed at the time of injury.^7–12 For example, in terms of age, only 50% of high school athletes (14–18 years of age) were reported to recover from SC in approximately 7 days, whereas 90% of adult athletes ≥18 years of age recovered in 7 days.^8,13–15 Regarding sex differences, Covassin et al¹⁶ observed that female high school athletes may take up to 14 days to recover in terms of memory and processing speed after concussion. In a separate study, Covassin et al¹² noted that concussed high school- and college-aged females consistently demonstrated higher symptom levels than male participants up to 14 days after concussion.Though the majority of concussion symptoms in older athletes resolve in ≤7 days of injury, approximately 10% of concussed athletes experience persistent symptoms up to 3 months after their diagnosis.¹⁷ Additionally, a subset of patients may experience 3 or more postconcussion symptoms for 3 months or longer, which is classified as postconcussion syndrome (PCS). Babcock et al¹⁸ found that 29% of pediatric concussion patients diagnosed in the emergency department for whom sport was the primary mechanism of injury (35%) were later diagnosed with PCS, which equates to 105 000 cases of pediatric PCS annually in the United States. The authors suggested that being able to prospectively identify candidates at risk for PCS would assist clinicians in discharge planning (eg, education, medications, and ongoing follow-up), ultimately resulting in improved patient outcomes.Studies examining predictors of SC recovery have usually addressed the dichotomy of typical recovery (7–13 days) versus protracted recovery.^3,12 Protracted recovery has been defined as resolution of SC lasting longer than 14,¹⁰ 21,¹¹ 45, or 90 days.^17,19 Several predictors, including loss of consciousness (LOC), posttraumatic amnesia (PTA), retrograde amnesia, total symptom severity, dizziness severity, and headache severity, have been associated with a 1.8- to 6-fold increase in risk for protracted recovery.^11,17,18 Of these predictors, LOC and amnesia are points of debate because of their infrequent occurrence and questionable relationship with injury severity and recovery.^8,11,20The objective of our study was to determine if the number of days an athlete reported concussion-related symptoms could be predicted from dependent variables derived from clinical measures commonly used to manage this injury. The ability to determine how many days an athlete will report SC-related symptoms may assist clinicians by allowing identification of athletes at risk for prolonged recoveries and institution of the appropriate medical and psychosocial infrastructure to assist in a full recovery.     

Investigation on cobalt‐oxide nanoparticles cyto‐genotoxicity and inflammatory response in two types of respiratory cells

The increasing use of cobalt oxide (Co₃O₄) nanoparticles (NPs) in several applications and the suggested genotoxic potential of Co‐oxide highlight the importance of evaluating Co₃O₄ NPs toxicity. Cyto‐genotoxic and inflammatory effects induced by Co₃O₄ NPs were investigated in human alveolar (A549), and bronchial (BEAS‐2B) cells exposed to 1–40 µg ml^–1. The physicochemical properties of tested NPs were analysed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cytotoxicity was studied to analyze cell viability (WST1 test) and membrane damage (LDH assay), direct/oxidative DNA damage was assessed by the Formamido‐pyrimidine glycosylase (Fpg)‐modified comet assay and inflammation by interleukin (IL)‐6, IL‐8 and tumor necrosis factor‐alpha (TNF‐α) release (ELISA). In A549 cells, no cytotoxicity was found, whereas BEAS‐2B cells showed a viability reduction at 40 µg ml^–1 and early membrane damage at 1, 5 and 40 µg ml–1. In A549 cells, direct and oxidative DNA damage at 20 and 40 µg ml^–1 were detected without any effects on cytokine release. In BEAS‐2B cells, significant direct DNA damage at 40 µg ml^–1 and significant oxidative DNA damage with a peak at 5 µg ml^–1, that was associated with increased TNF‐α release at 1 µg ml^–1 after 2 h and increased IL‐8 release at 20 µg ml^–1 after 24 h, were detected. The findings show in the transformed alveolar cells no cytotoxicity and genotoxic/oxidative effects at 20 and 40 µg ml^–1. In normal bronchial cells, moderate cytotoxicity, direct DNA damage only at the highest concentration and significant oxidative‐inflammatory effects at lower concentrations were detected. The findings confirm the genotoxic‐oxidative potential of Co₃O₄ NPs and show greater sensitivity of BEAS‐2B cells to cytotoxic and oxidative‐inflammatory effects suggesting the use of different cell lines and multiple end‐points to elucidate Co₃O₄ NPs toxicity. Copyright © 2015 John Wiley & Sons, Ltd.     

Contextual Information Drives the Reconsolidation-Dependent Updating of Retrieved Fear Memories

Stored memories enter a temporary state of vulnerability following retrieval known as ‘reconsolidation'', a process that can allow memories to be modified to incorporate new information. Although reconsolidation has become an attractive target for treatment of memories related to traumatic past experiences, we still do not know what new information triggers the updating of retrieved memories. Here, we used biochemical markers of synaptic plasticity in combination with a novel behavioral procedure to determine what was learned during memory reconsolidation under normal retrieval conditions. We eliminated new information during retrieval by manipulating animals'' training experience and measured changes in proteasome activity and GluR2 expression in the amygdala, two established markers of fear memory lability and reconsolidation. We found that eliminating new contextual information during the retrieval of memories for predictable and unpredictable fear associations prevented changes in proteasome activity and glutamate receptor expression in the amygdala, indicating that this new information drives the reconsolidation of both predictable and unpredictable fear associations on retrieval. Consistent with this, eliminating new contextual information prior to retrieval prevented the memory-impairing effects of protein synthesis inhibitors following retrieval. These results indicate that under normal conditions, reconsolidation updates memories by incorporating new contextual information into the memory trace. Collectively, these results suggest that controlling contextual information present during retrieval may be a useful strategy for improving reconsolidation-based treatments of traumatic memories associated with anxiety disorders such as post-traumatic stress disorder.     

Low-intensity oral anticoagulant plus low-dose aspirin during the first six months versus standard-intensity oral anticoagulant therapy after mechanical heart valve replacement: a pilot study of low-intensity warfarin and aspirin in cardiac prostheses (LIWACAP).

The objective of this study was to evaluate the safety and efficacy of low-intensity warfarin treatment plus aspirin during the first 6 months after surgery in patients undergoing heart valve substitution with mechanical prostheses. Vitamin K antagonists (VKA) are able to reduce but not eliminate thrombosis and systemic embolism in patients with mechanical heart valves. The intensity of treatment and additional use of aspirin in these patients is still controversial. Consecutive patients undergoing aortic or mitral valve replacement (or a combination of the two) with mechanical prostheses were invited to participate in the study. After stratifying for site of prosthesis, patients were randomized to receive low intensity VKA treatment (target INR 2.5) plus aspirin (100 mg/day) for the first six months (Group A) or standard-intensity (INR target 3.7) VKA treatment (Group B). Mean follow-up was 1.5 years. Principal outcome events were systemic embolism, major bleeding, and vascular death. A total of 94 patients in Group A and 104 in Group B were randomized and followed up for 144 and 163 patient years, respectively. There were 5 (5%) events in Group A (4 major bleeding events and 1 vascular death) and 4 (4%) in group B (2 major bleeding events and 2 ischemic stroke). All the events except 1 occurred within the first 6 months after surgery. Cumulative incidence of primary outcome events was 5.8% (95% CI 0.9 to 10.7) in Group A and 4.3% (95% CI 0.2 to 8.4) in Group B (p=0.6). Low-intensity treatment plus aspirin during the first six months after surgery appears to be as effective and safe as moderate-high-intensity anticoagulation.     

West Nile virus encephalitis causing fatal CNS toxicity after hematopoietic stem cell transplantation

We describe here a patient who died of progressive CNS deterioration following allogeneic stem cell transplant with West Nile virus as the sole pathogen on the cerebrospinal fluid and brain tissue analysis. A 50-year-old male with Philadelphia chromosome-positive acute lymphocytic leukemia (ALL) underwent allogeneic PBSCT from his HLA identical sister. After engraftment, the patient developed fever with progressive and ultimately fatal neurological deterioration. Imaging studies of the brain including CT and MRI scans were remarkable for mild low attenuation lesions of the white matter. CSF analysis was negative for neoplastic cells, bacteria, AFB, CMV, HSV, fungal infections and leukemic relapse. However, serological analysis of both the serum and CSF was positive for West Nile virus-specific IgM antibodies. At autopsy, West Nile virus PCR and cultures were positive in the mid-brain tissue. Electron micrographs showed evidence of viral particles. Given the recent increase in the spread of West Nile virus infections and the increased susceptibility of BMT patients to infectious complications, West Nile virus encephalitis should be considered in patients undergoing transplantation.     

QT-interval prolongation in right precordial leads: an additional electrocardiographic hallmark of Brugada syndrome

OBJECTIVES: The aim of this study was to evaluate whether the occurrence of the Brugada Syndrome typical electrocardiogram (ECG) pattern (i.e., right bundle branch block, coved-type ST-segment elevation, and T-wave inversion in the right precordial leads) is characterized by a concomitant lengthening of QT intervals in the right precordial leads. BACKGROUND: It has been suggested that the typical ECG pattern of Brugada syndrome is due to a decreased net inward current during phase 1 of the action potential, which also leads to its prolongation in the right epicardium. METHODS: Thirty-two subjects (19 males) age 37 +/- 15 years with a suspicious baseline ECG, or who were relatives of Brugada syndrome patients, underwent 12-lead ECG before and after the administration of flecainide. RESULTS: The flecainide test was negative in 14 and positive in 18 subjects. After flecainide administration, the positive ECGs were characterized by a greater QT interval corrected for heart rate (QTc) prolongation in the right precordial leads than that in the negative ECGs (78.2 +/- 35.5 ms vs. 22.0 +/- 28.4 ms in V(1) and 107.1 +/- 43.8 ms vs. 26.7 +/- 30.1 ms in V(2); p < 0.01), whereas there was no difference in the QTc prolongation in the left precordial leads (55.2 +/- 25.3 ms vs. 35.1 +/- 28.1 ms in V(5) and 53.1 +/- 32.8 ms vs. 27.3 +/- 22.4 ms in V(6); p = NS). CONCLUSIONS: In accordance with the electrophysiological background, the typical ECG pattern of Brugada syndrome is also characterized by a considerable prolongation of the QT interval in right precordial leads.     

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Annals of Nuclear Medicine - [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis...     

Selective Na+/H+ exchange inhibition by cariporide reduces liver fibrosis in the rat

The aim of this study was to evaluate the effect of cariporide, a selective Na(+)/H(+) exchange inhibitor, on isolated and cultured hepatic stellate cells (HSCs) and in 2 in vivo models of rat liver fibrosis. Platelet-derived growth factor (PDGF)-induced HSC proliferation, evaluated by measuring the percentage of bromodeoxyuridine-positive cells, was significantly inhibited by cariporide, with a maximal effect at 10 micromol/L. Incubation with cariporide did not inhibit PDGF-induced extracellular-regulated kinase 1/2 (ERK1/2), Akt (a downstream component of the phosphatidylinositol [PI]-3 kinase pathway), and protein kinase C (PKC) activation but reduced PDGF-induced activation of the Na(+)/H(+) exchanger, with a maximal effect at 10 micromol/L. Rats treated with dimethylnitrosamine (DMN; 10 mg/kg) for 1 and 5 weeks received a diet with or without 6 ppm cariporide. Treatment with cariporide reduced the degree of liver injury, as determined by alanine aminotransferase (ALT) values, also when administered after the induction of hepatic damage. This was associated with reduced HSC activation and proliferation and reduced collagen deposition, as determined by morphometric evaluation of alpha-smooth muscle actin (SMA)/proliferating cell nuclear antigen-positive cells and percentage of Sirius red-positive parenchyma, respectively. Moreover, cariporide was also able to reduce alpha(1)I procollagen messenger RNA (mRNA) expression. Similar effects were observed in bile duct-ligated (BDL) rats. In conclusion, selective inhibition of the Na(+)/H(+) exchanger by cariporide may represent an effective therapeutic strategy in the treatment of hepatic fibrosis.