Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football

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Clinicopathological Evaluation, Traumatic Encephalopathy , Football
2017 Jul 25;318(4):360-370. doi: 10.1001/jama.2017.8334.

Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football.

Abstract

IMPORTANCE:

Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE).

OBJECTIVE:

To determine the neuropathological and clinical features of deceased football players with CTE.

DESIGN, SETTING, AND PARTICIPANTS:

Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history.

EXPOSURES:

Participation in American football at any level of play.

MAIN OUTCOMES AND MEASURES:

Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia.

RESULTS:

Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia.

CONCLUSIONS AND RELEVANCE:

In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.

PMID:
28742910

Clinicopathological Evaluation, Traumatic Encephalopathy , Football

DOI:
10.1001/jama.2017.8334

Central Bright Spot Sign: A Potential New MR Imaging Sign for the Early Diagnosis of Anterior Ischemic Optic Neuropathy due to Giant Cell Arteritis.

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Central Bright Spot Sign,MRI,Ischemic Optic Neuropathy,Giant Cell Arteritis

AJNR Am J Neuroradiol. 2017 May 11. doi: 10.3174/ajnr.A5205. [Epub ahead of print]

The Central Bright Spot Sign: A Potential New MR Imaging Sign for the Early Diagnosis of Anterior Ischemic Optic Neuropathy due to Giant Cell Arteritis.

Abstract

BACKGROUND AND PURPOSE:

A rapid identification of the etiology of anterior ischemic optic neuropathy is crucial because it determines therapeutic management. Our aim was to assess MR imaging to study the optic nerve head in patients referred with anterior ischemic optic neuropathy, due to either giant cell arteritis or the nonarteritic form of the disease, compared with healthy subjects.

MATERIALS AND METHODS:

Fifteen patients with giant cell arteritis-related anterior ischemic optic neuropathy and 15 patients with nonarteritic anterior ischemic optic neuropathy from 2 medical centers were prospectively included in our study between August 2015 and May 2016. Fifteen healthy subjects and patients had undergone contrast-enhanced, flow-compensated, 3D T1-weighted MR imaging. The bright spot sign was defined as optic nerve head enhancement with a 3-grade ranking system. Two radiologists and 1 ophthalmologist independently performed blinded evaluations of MR imaging sequences with this scale. Statistical analysis included interobserver agreement.

RESULTS:

MR imaging scores were significantly higher in patients with giant cell arteritis-related anterior ischemic optic neuropathy than in patients with nonarteritic anterior ischemic optic neuropathy (P ≤ .05). All patients with giant cell arteritis-related anterior ischemic optic neuropathy (15/15) and 7/15 patients with nonarteritic anterior ischemic optic neuropathy presented with the bright spot sign. No healthy subjects exhibited enhancement of the anterior part of the optic nerve. There was a significant relationship between the side of the bright spot and the side of the anterior ischemic optic neuropathy (P ≤ .001). Interreader agreement was good for observers (κ = 0.815).

CONCLUSIONS:

Here, we provide evidence of a new MR imaging sign that identifies the acute stage of giant cell arteritis-related anterior ischemic optic neuropathy; patients without this central bright spot sign always had a nonarteritic pathophysiology and therefore did not require emergency corticosteroid therapy.

Comparison of laser in situ ketatomileusis and photorefractive keratectomy for myopia using a mixed-effects model.

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Lasik,photorefractive keratectomy,myopia,photorefractive-keratectomy,myopia. PLoS One. 2017 Mar 31;12(3):e0174810. doi: 10.1371/journal.pone.0174810. eCollection 2017.laser in situ ketatomileusis,photorefractive keratectomy,myopia,
Comparison of laser in situ ketatomileusis and photorefractive keratectomy for myopia using a mixed-effects model.

Mori Y1, Miyata K1, Ono T1, Yagi Y1, Kamiya K2, Amano S3.
Author information
Abstract
PURPOSE:
To compare the results of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for myopia using a mixed-effects model.
METHODS:
This comparative retrospective study was conducted in 1,127 eyes of 579 patients after LASIK and 270 eyes of 144 patients after PRK who had two or more postoperative follow-ups after 3 months. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refractive spherical equivalent (MRSE), percentage of eyes within ± 0.5 diopters (D) and ± 1.0 D of targeted refraction, and central corneal thickness were compared between PRK and LASIK groups using a mixed-effects model.
RESULTS:
Compared with the LASIK group, UCVA in the PRK group was significantly worse in the initial year but was significantly better after 4 years. The average BSCVA was not significantly different between the LASIK and PRK groups after 4 years. The average gain of BSCVA in the PRK group was significantly larger than that of the LASIK group after 2 years. MRSE in the LASIK and PRK groups showed a gradual myopic shift until 6 years after surgery. After 6 years, MRSE in the PRK group remained stable whereas MRSE in the LASIK group continued a myopic shift. The percentages of eyes within ± 0.5 D or ± 1.0 D in the LASIK group were significantly higher than those in the PRK group at 3 months but were significantly lower than those in the PRK group at 10 years.
CONCLUSIONS:
PRK for myopia shows better efficacy than LASIK for myopia after 4 years.

Lasik,photorefractive keratectomy,myopia,
Surgeon performing laser treatment. Not from article

What factors influence uptake of retinal screening among young adults with type 2 diabetes? A qualitative study informed by the theoretical domains framework.

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Diabetic retinopathy, Qualitative research,Theoretical domains framework, Type 2 diabetes, Young adults.  J Diabetes Complications. 2017 Mar 14. pii: S1056-8727(16)30935-7. doi: 10.1016/j.jdiacomp.2017.02.020. [Epub ahead of print].

What factors influence uptake of retinal screening among young adults with type 2 diabetes? A qualitative study informed by the theoretical domains framework.

Lake AJ1, Browne JL2, Rees G3, Speight J4.
Author information
Abstract
AIMS:
Young adults with type 2 diabetes (T2D, 18-39years) face increased risk of vision loss from diabetic retinopathy (DR). Retinal screening is essential to detect DR, yet screening rates for this group are low and little is known about the underlying factors influencing this important behavior. Using the theoretical domains framework (TDF) to guide data collection and analysis, we explored screening barriers and facilitator, contrasting them with a comparator group of older adults with T2D (40+ years).
METHODS:
Thirty semi-structured telephone interviews (10 younger, 20 older adults) were conducted. Data were coded into TDF domains with salience identified by “frequency” of reference. Screening facilitators and barriers were systematically compared between groups.
RESULTS:
Although many screening facilitators and barriers were shared by younger and older adults, additional factors highly relevant to the former included: social comparison with others (‘social influences’); concern for the impact on the family unit, unrealistic optimism and perceived invulnerability (‘beliefs about consequences’); lack of time and financial resources (‘environmental context and resources’), and DR misconceptions (‘knowledge’).
CONCLUSIONS:
This study demonstrated that young adult retinal screening behavior was influenced by additional social cognitive factors compared to older adults, providing a first-step evidence base for clinicians and other health professionals, and potential targets for future eye health and retinal screening interventions.

Diabetic retinopathy, Qualitative research,Theoretical domains framework, Type 2 diabetes, Young adults
Bad diabetic retinopathy as might be seen in the people of this study

 

An Eye Popping Case of Orbital Necrotizing Fasciitis Treated with Antibiotics, Surgery, and Hyperbaric Oxygen Therapy.

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Am J Case Rep. 2017 Apr 1;18:329-333.
An Eye Popping Case of Orbital Necrotizing Fasciitis Treated with Antibiotics, Surgery, and Hyperbaric Oxygen Therapy. Orbital Necrotizing Fasciitis,Antibiotics, Surgery,Hyperbaric Oxygen Therapy

Singam NV1, Rusia D2, Prakash R1.
Author information
Abstract
BACKGROUND Necrotizing fasciitis (NF) of the orbit is a rare and deadly condition that requires prompt surgical and medical management to decrease morbidity and mortality. CASE REPORT Here we present an interesting case of an individual who developed fulminant NF of the left orbit requiring emergent surgical intervention, antibiotics, and subsequent hyperbaric oxygen therapy in an attempt to save the eye. CONCLUSIONS With an early and aggressive multifaceted approach using antibiotics, surgery, and hyperbaric oxygen it may be possible to preserve eye structure and function. Without treatment NF is a rapidly progressive condition and can result in significant morbidity.

 

Am J Case Rep. 2017 Apr 1;18:329-333.
An Eye Popping Case of Orbital Necrotizing Fasciitis Treated with Antibiotics, Surgery, and Hyperbaric Oxygen Therapy. Orbital Necrotizing Fasciitis,Antibiotics, Surgery,Hyperbaric Oxygen Therapy

Singam NV1, Rusia D2, Prakash R1.
Author information
Abstract
BACKGROUND Necrotizing fasciitis (NF) of the orbit is a rare and deadly condition that requires prompt surgical and medical management to decrease morbidity and mortality. CASE REPORT Here we present an interesting case of an individual who developed fulminant NF of the left orbit requiring emergent surgical intervention, antibiotics, and subsequent hyperbaric oxygen therapy in an attempt to save the eye. CONCLUSIONS With an early and aggressive multifaceted approach using antibiotics, surgery, and hyperbaric oxygen it may be possible to preserve eye structure and function. Without treatment NF is a rapidly progressive condition and can result in significant morbidity.

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial.

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opticinumab, optic neuritis, RENEW, michael duplessie

Lancet Neurol. 2017 Mar;16(3):189-199. doi: 10.1016/S1474-4422(16)30377-5. Epub 2017 Feb 15.
Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial.
Cadavid D1, Balcer L2, Galetta S2, Aktas O3, Ziemssen T4, Vanopdenbosch L5, Frederiksen J6, Skeen M7, Jaffe GJ8, Butzkueven H9, Ziemssen F10, Massacesi L11, Chai Y12, Xu L12, Freeman S12; RENEW Study Investigators.
Author information
Abstract
BACKGROUND:
The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode.
METHODS:
This randomised, double-blind, placebo-controlled, phase 2 study (RENEW) was done at 33 sites in Australia, Canada, and Europe in participants (aged 18-55 years) with a first unilateral acute optic neuritis episode within 28 days from study baseline. After treatment with high-dose methylprednisolone (1 g/day, intravenously, for 3-5 days), participants were assigned with a computer-generated sequence with permuted block randomisation (1:1) using a centralised interactive voice and web response system to receive 100 mg/kg opicinumab intravenously or placebo once every 4 weeks (six doses) and followed up to week 32. All study participants and all study staff, including the central readers, were masked to treatment assignment apart from the pharmacist responsible for preparing the study treatments and the pharmacy monitor at each site. The primary endpoint was remyelination at 24 weeks, measured as recovery of affected optic nerve conduction latency using full-field visual evoked potential (FF-VEP) versus the unaffected fellow eye at baseline. Analysis was by intention-to-treat (ITT); prespecified per-protocol (PP) analyses were also done. This study is registered with ClinicalTrials.gov, number NCT01721161.
FINDINGS:
The study was done between Dec 21, 2012, and Oct 21, 2014. 82 participants were enrolled, and 41 in each group comprised the ITT population; 33 participants received opicinumab and 36 received placebo in the PP population. Adjusted mean treatment difference of opicinumab versus placebo was -3·5 ms (17·3 vs 20·8 [95% CI -10·6 to 3·7]; 17%; p=0·33) in the ITT population, and -7·6 ms in the PP population (14·7 vs 22·2 [-15·1 to 0·0]; 34%; p=0·050) at week 24 and -6·1 ms (15·1 vs 21·2 [-12·7 to 0·5]; 29%; p=0·071) in the ITT population and -9·1 ms (13·2 vs 22·4 [-16·1 to -2·1]; 41%; p=0·011) in the PP population at week 32. The overall incidence (34 [83%] of 41 in each group) and severity of adverse events (two [5%] of 41 severe adverse events with placebo vs three [7%] of 41 with opicinumab) were similar between groups and no significant effects on brain MRI measures were noted in either group (mean T2 lesion volume change, 0·05 mL [SD 0·21] for placebo vs 0·20 mL [0·52] with opicinumab; 27 [77%] of 35 participants with no change in gadolinium-enhancing [Gd+] lesion number with opicinumab vs 27 [79%] of 34 with placebo; mean 0·4 [SD 0·79 for the placebo group and 0·85 for the opicinumab group] new Gd+ lesions per participant in both groups). Treatment-related serious adverse events were reported in three (7%) of 41 participants in the opicinumab group (hypersensitivity [n=2], asymptomatic increase in transaminase concentrations [n=1]) and none of the participants in the placebo group.
INTERPRETATION:
Remyelination did not differ significantly between the opicinumab and placebo groups in the ITT population at week 24. However, results from the prespecified PP population suggest that enhancing remyelination in the human CNS with opicinumab might be possible and warrant further clinical investigation.

Aqueous Humor Penetration and Biological Activity of Moxifloxacin 0.5% Ophthalmic Solution Alone or with Dexamethasone 0.1.

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J Ocul Pharmacol Ther. 2017 Mar;33(2):98-102. doi: 10.1089/jop.2016.0126.
Aqueous Humor Penetration and Biological Activity of Moxifloxacin 0.5% Ophthalmic Solution Alone or with Dexamethasone 0.1.
Gomes RL1,2, Viana RG2, Melo LA Jr1,2, Cruz AC3, Suenaga EM3, Kenyon KR4, Campos M1,2.
Author information
Abstract
PURPOSE:
To compare aqueous humor concentrations of topically applied moxifloxacin 0.5% ophthalmic solution alone or in combination with dexamethasone 0.1% and to correlate these concentrations with the minimum inhibitory concentrations (MICs) for common endophthalmitis-causing organisms.
METHODS:
Sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% alone or moxifloxacin 0.5% combined with dexamethasone. For both groups, 1 drop of the test solution was instilled 4 times daily 1 day preoperatively and 1 drop 1 h preoperatively. An aqueous humor sample obtained immediately before paracentesis was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin concentration.
RESULTS:
The mean concentrations of moxifloxacin were 986.6 ng/mL in the moxifloxacin with dexamethasone group and 741.3 ng/mL in the moxifloxacin group (P = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (P = 0.06).
CONCLUSION:
Aqueous humor moxifloxacin concentrations were higher when topically administrated in combination with dexamethasone compared to the moxifloxacin alone. However, this difference was not statistically significant. Nevertheless, the MICs of the most common pathogens associated with endophthalmitis were exceeded in both study groups.
KEYWORDS:
antibiotics; aqueous humor; corneal permeability; fluoroquinolone ophthalmic solutions; steroids

When do myopia genes have their effect? Comparison of genetic risks between children and adults

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myopia, myopic genes, genetic risks
Genet Epidemiol. 2016 Sep 9. doi: 10.1002/gepi.21999. [Epub ahead of print]

When do myopia genes have their effect? Comparison of genetic risks between children and adults.

Abstract

Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged <10 years; 5,000 aged 10-25 years; and 16,274 aged >25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (AL) and corneal radius (CR). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome-wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus AL/CR was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni-corrected. In the age group <10 years, three loci (GJD2, CHRNG, ZIC2) were associated with AL/CR. In the age group 10-25 years, four loci (BMP2, KCNQ5, A2BP1, CACNA1D) were associated; and in adults 20 loci were associated. Association with GRS increased with age; β = 0.0016 per risk allele (P = 2 × 10-8 ) in <10 years, 0.0033 (P = 5 × 10-15 ) in 10- to 25-year-olds, and 0.0048 (P = 1 × 10-72 ) in adults. Genes with strongest effects (LAMA2, GJD2) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.

Creation of a refractive lens within an existing intraocular lens using a femtosecond laser.

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refractive lens,intraocular lens,femtosecond laser
J Cataract Refract Surg. 2016 Aug;42(8):1207-15. doi: 10.1016/j.jcrs.2016.05.005.

Creation of a refractive lens within an existing intraocular lens using a femtosecond laser.

Abstract

PURPOSE:

To assess the efficiency and effectiveness of the technology that creates a hydrophilicity-based refractive index change within a standard intraocular lens (IOL) to alter the refractive characteristics of the IOL.

SETTING:

Perfect Lens LLC, Irvine, California, USA.

DESIGN:

Experimental study.

METHODS:

The IOL used in this experiment was a standard hydrophobic model (EC-1Y). The refractive index of the material was changed by exposure of the material to a femtosecond laser and the subsequent absorption of water by the material. An experimental system using a femtosecond laser, an acoustic-optic modulator, beam-shaping optics, a scan system, and an objective lens was used to create the refractive index change within the IOL. Experiments were performed to determine the optimum wavelength, energy per pulse, and line spacing to produce the refractive index shaping lens. A power and modulation transfer function (MTF) measurement device for refractive and diffractive IOLs was used to measure the diopter and MTF before and after the creation of the refractive index shaping lens.

RESULTS:

The technology successfully altered the refractive characteristics of the IOL. The refractive index change altered the diopter (D) of the IOL (to within ±0.1 D of the targeted change) without significant diminution in the MTF (<0.1 or MTF ≥0.51 for the 100 lp/mm measurement).

CONCLUSION:

The refractive properties of an IOL can be altered by building a refractive index shaping lens within an IOL using a femtosecond laser with minimal diminution in MTF.

Long-term side effects of glucocorticoids.

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corticosteroids,glucocorticoids,immunosuppression,side effects
Expert Opin Drug Saf. 2016 Jan 20. [Epub ahead of print]

Long-term side effects of glucocorticoids.

Abstract

INTRODUCTION:

Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible. Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment. Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

KEYWORDS:

corticosteroids; glucocorticoids; immunosuppression; side effects

Expert Opin Drug Saf. 2016 Jan 20. [Epub ahead of print]

Long-term side effects of glucocorticoids.

Abstract

INTRODUCTION:

Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible. Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment. Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

KEYWORDS:

corticosteroids; glucocorticoids; immunosuppression; side effects

INTRODUCTION:

Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible. Areas Covered: This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment. Expert Opinion: The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

KEYWORDS:

corticosteroids; glucocorticoids; immunosuppression; side effects