Hypertensive retinopathy and cardiovascular disease risk: 6 population-based cohorts meta-analysis.

Background: The cardiovascular risk associated with different levels of hypertensive retinopathy, including mild, remains unclear. We performed an individual participant meta-analysis from 6 population-based cohort studies to determine the relationship of hypertensive retinopathy with incident cardiovascular outcomes. Methods: We identified cohort studies that objectively assessed hypertensive retinopathy from photographs, documented incident cardiovascular outcomes, and were population-based. Six studies contributed data from 11,013 individuals at baseline with 5-13 years follow-up. Participants were recruited if they had hypertension and did not have confounding conditions such as diabetic retinopathy. Main outcome measures were incident coronary heart disease (CHD), stroke and a composite endpoint of cardiovascular disease (CHD or stroke). Pooled estimates of incident risk ratios (IRR) were obtained after adjusting for age, gender, systolic blood pressure, serum total cholesterol, high density lipoprotein and smoking. Results: Among eligible participants with hypertension and without diabetes, there were 1018/9662 (10.5%) incident CHD events, 708/11,013 (6.4%) incident stroke events and 1317/9378 (14.0%) incident CVD events. Mild hypertensive retinopathy was associated with increased risk of CVD (IRR 1.13, 95% CI 1.00 to 1.27) and CHD (IRR 1.17, 95% CI 1.02 to 1.34) but not stroke; moderate hypertensive retinopathy was associated with increased risk of CVD (IRR 1.25 95% CI 1.02 to 1.53) but not stroke or CHD individually. Conclusions: In persons with hypertension, both mild and moderate hypertensive retinopathy were associated with higher CVD risk.

Systemic Immune Profile Predicts the Development of Infections in Patients with Spinal Cord Injuries.

Patients with spinal cord injury (SCI) frequently develop infections that may affect quality of life, be life-threatening, and impair their neurological recovery in the acute and subacute injury phases. Therefore, identifying patients with SCI at risk for developing infections in this stage is of utmost importance. We determined the systemic levels of immune cell populations, cytokines, chemokines, and growth factors in 81 patients with traumatic SCI at 4 weeks after injury and compared them with those of 26 age-matched healthy control subjects. Patients who developed infections between 4 and 16 weeks after injury exhibited higher numbers of neutrophils and eosinophils, as well as lower numbers of lymphocytes and eotaxin-1 (CCL11) levels. Accordingly, lasso logistic regression showed that incomplete lesions (American Spinal Injury Association Impairment Scale [AIS] C and D grades), the levels of eotaxin-1, and the number of lymphocytes, basophils, and monocytes are predictive of lower odds for infections. On the other hand, the number of neutrophils and eosinophils as well as, in a lesser extent, the levels of IP-10 (CXCL10), MCP-1 (CCL2), BDNF [brain-derived neurotrophic factor], and vascular endothelial growth factor [VEGF]-A, are predictors of increased susceptibility for developing infections. Overall, our results point to systemic immune disbalance after SCI as predictors of infection in a period when infections may greatly interfere with neurological and functional recovery and suggest new pathways and players to further explore novel therapeutic strategies.

Allergy-induced systemic inflammation impairs tendon quality.

BACKGROUND: Treatment of degenerating tendons still presents a major challenge, since the aetiology of tendinopathies remains poorly understood. Besides mechanical overuse, further known predisposing factors include rheumatoid arthritis, diabetes, obesity or smoking all of which combine with a systemic inflammation. METHODS: To determine whether the systemic inflammation accompanying these conditions contributes to the onset of tendinopathy, we studied the effect of a systemic inflammation induced by an allergic episode on tendon properties. To this end, we induced an allergic response in mice by exposing them to a timothy grass pollen allergen and subsequently analysed both their flexor and Achilles tendons. Additionally, we analysed data from a health survey comprising data from more than 10.000 persons for an association between the occurrence of an allergy and tendinopathy. FINDINGS: Biomechanical testing and histological analysis revealed that tendons from allergic mice not only showed a significant reduction of both elastic modulus and tensile stress, but also alterations of the tendon matrix. Moreover, treatment of 3D tendon-like constructs with sera from allergic mice resulted in a matrix-remodelling expression profile and the expression of macrophage-associated markers and matrix metalloproteinase 2 (MMP2) was increased in allergic Achilles tendons. Data from the human health study revealed that persons suffering from an allergy have an increased propensity to develop a tendinopathy. INTERPRETATION: Our study demonstrates that the presence of a systemic inflammation accompanying an allergic condition negatively impacts on tendon structure and function. FUNDING: This study was financially supported by the Fund for the Advancement of Scientific Research at Paracelsus Medical University (PMU-FFF E-15/22/115-LEK), by the Land Salzburg, the Salzburger Landeskliniken (SALK, the Health Care Provider of the University Hospitals Landeskrankenhaus and Christian Doppler Klinik), the Paracelsus Medical University, Salzburg and by unrestricted grants from Bayer, AstraZeneca, Sanofi-Aventis, Boehringer-Ingelheim.

Evaluation of symptomatic degenerative lumbar stenosis with probable determining factors / Avaliação da estenose lombar degenerativa sintomática com fatores determinantes prováveis / Evaluación de la estenosis lumbar degenerativa sintomática con probables factores determinantes

ABSTRACT Objective: To evaluate degenerative lumbar stenosis in symptomatic patients submitted to surgeryand the correlation between probable determining factors. Methods: A retrospective descriptive study in which themagnetic resonance images of 73 patients with degenerative stenosis,who underwent surgeries involving 141 levels performed by a single surgeon at the Hospital Ortopédico de Passo Fundo from 2015 to 2018, were evaluated. The patients were stratified by the degree of facet tropism, facet arthrosis, disc degeneration, and operated side, as well as by epidemiological data such as age, sex, etc. Tropism was measured using the Karacan method and evaluated numerically and categorically. Disc degeneration was classified by Pfirrmann and facet arthrosis by Weishaupt. To analyze and obtain the results, the Chi-square test and ANOVA were used with the SPSS statistical program, version 18.0. Results: Statistical significance was found in the relationship between facet tropism and disc degeneration (p=0.026) at the L4-L5 level. No correlation was found between tropism and facet arthrosis (p=0.161) or tropism and the operated side (p=0.573). Conclusion: The degree of tropism directly influences disc degeneration and greater asymmetries are related to more severe degenerations. Although tropism has not shown a statistically significant correlation with the operated side (p=0.573), it is believed that further studies should be carried out on this correlation. Level of evidence II; Retrospective study.

RESUMO Objetivo: Avaliar a estenose lombar degenerativa em pacientes sintomáticos submetidos à cirurgia, analisando a correlação entre fatores determinantes prováveis. Métodos: Estudo retrospectivo descritivo, no qual foram avaliados exames de ressonância nuclear magnética de 73 pacientes, totalizando 141 níveis com estenose degenerativa submetidos a tratamento cirúrgico por um único cirurgião do Hospital Ortopédico de Passo Fundo, de 2015 até 2018. Os pacientes foram estratificados de acordo com grau do tropismo facetário, artrose facetária, degeneração discal e lado operado, assim como com dados epidemiológicos como idade, sexo, etc. O tropismo foi aferido pelo método de Karacan e avaliado de forma numérica e categórica. A degeneração discal foi classificada por Pfirrmann e a artrose facetária por Weishaupt. Para análise e obtenção dos resultados foi utilizado o teste do qui-quadrado e ANOVA com oprograma estatístico SPSS versão 18.0. Resultados: Verificou-se significância estatística na relação entre tropismo facetário e degeneração discal (p=0,026) no nível L4-L5. Não foi encontrada correlação entre tropismo e artrose facetária (p=0,161) ou tropismo e lado operado(p=0,573). Conclusões: O grau de tropismo influencia diretamente a degeneração discal, sendo que as assimetrias maiores estão relacionadas a degenerações mais graves. Embora o tropismo não tenha demonstrado correlação estatística significativa com o lado operado (p=0,573), acredita-se que deverão ser realizados novos estudos sobre essa correlação. Nível de evidência II; Estudo retrospectivo.

RESUMEN Objetivo: Evaluar la estenosis lumbar degenerativa en pacientes sintomáticos sometidos a cirugía, analizando la correlación entre probables factores determinantes.. Métodos: Estudio retrospectivo descriptivo, en el que se evaluaronlos exámenes de resonancia magnética nuclear de 73 pacientes, totalizando 141 niveles con estenosis degenerativa sometidos a tratamiento quirúrgico por un único cirujano en el Hospital Ortopédico de Passo Fundo, de 2015 a 2018. Los pacientes fueron estratificados según elgrado de tropismo facetario, artrosis facetaria, degeneración discal y lado operado, así como con datos epidemiológicos como edad, sexo, etc. El tropismo se midió utilizando el método de Karacan y se evaluó numérica y categóricamente. La degeneración discal fue clasificada por Pfirrmann y la artrosis facetaria por Weishaupt. Para analizar y obtener los resultados se utilizó la prueba de chi-cuadrado y ANOVA a través del programa estadístico SPSS versión 18.0. Resultados: Se encontró significación estadística en la relación entre el tropismo facetario y la degeneración discal (p=0,026) en el nivel L4-L5. No se encontró correlación entre el tropismo y la artrosis facetaria (p=0,161) ni el tropismo y el lado operado (p=0,573). Conclusión: El grado de tropismo influye directamente en la degeneración discal, y las mayores asimetrías se relacionan con degeneraciones más severas. Aunque el tropismo no ha mostrado una correlación estadísticamente significativa con el lado operado (p=0,573), se cree que deberían realizarse más estudios sobre esta correlación. Nivel de evidencia II; Estudio retrospectivo.

Genome-Wide Association Study of Peripheral Artery Disease.

BACKGROUND: Peripheral artery disease (PAD) affects >200 million people worldwide and is associated with high mortality and morbidity. We sought to identify genomic variants associated with PAD overall and in the contexts of diabetes and smoking status. METHODS: We identified genetic variants associated with PAD and then meta-analyzed with published summary statistics from the Million Veterans Program and UK Biobank to replicate their findings. Next, we ran stratified genome-wide association analysis in ever smokers, never smokers, individuals with diabetes, and individuals with no history of diabetes and corresponding interaction analyses, to identify variants that modify the risk of PAD by diabetic or smoking status. RESULTS: We identified 5 genome-wide significant (Passociation ≤5×10-8) associations with PAD in 449 548 (Ncases=12 086) individuals of European ancestry near LPA (lipoprotein [a]), CDKN2BAS1 (CDKN2B antisense RNA 1), SH2B3 (SH2B adaptor protein 3) - PTPN11 (protein tyrosine phosphatase non-receptor type 11), HDAC9 (histone deacetylase 9), and CHRNA3 (cholinergic receptor nicotinic alpha 3 subunit) loci (which overlapped previously reported associations). Meta-analysis with variants previously associated with PAD showed that 18 of 19 published variants remained genome-wide significant. In individuals with diabetes, rs116405693 at the CCSER1 (coiled-coil serine rich protein 1) locus was associated with PAD (odds ratio [95% CI], 1.51 [1.32-1.74], Pdiabetes=2.5×10-9, Pinteractionwithdiabetes=5.3×10-7). Furthermore, in smokers, rs12910984 at the CHRNA3 locus was associated with PAD (odds ratio [95% CI], 1.15 [1.11-1.19], Psmokers=9.3×10-10, Pinteractionwithsmoking=3.9×10-5). CONCLUSIONS: Our analyses confirm the published genetic associations with PAD and identify novel variants that may influence susceptibility to PAD in the context of diabetes or smoking status.

Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: The REMOVAL trial.

AIM: To determine whether metformin's effects on carotid artery intima-media thickness (cIMT) in type 1 diabetes differ according to smoking status. METHODS: Regression model effect estimates for the effect of metformin versus placebo (double-blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. RESULTS: In 428 randomized participants (227 never-smokers, 201 ever-smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.012 mm, 95% CI -0.021 to -0.002; p = .0137) but not in ever-smokers (0.003 mm, 95% CI -0.008 to 0.014; p = .5767); and similarly in non-current smokers (-0.008 mm, 95% CI -0.015 to -0.00001; p = .0497) but not in current smokers (0.013 mm, 95% CI -0.007 to 0.032; p = .1887). Three-way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p = .0373, prespecified) and non-current versus current smoking (p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never-smokers (-0.020 mm, 95% CI -0.034 to -0.006; p = .0067) but not in ever-smokers (-0.006 mm, 95% CI -0.020 to 0.008; p = .4067), although this analysis was not supported by a significant three-way interaction term. CONCLUSIONS: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes.

Incidence of Hearing Impairment and Changes in Pure-Tone Average Across Generations.

Importance: Age-adjusted prevalence of hearing impairment (HI) decreased across generations in the 20th century, suggesting that HI is partially preventable. It is not known whether HI incidence differs by generation. Objectives: To examine whether HI incidence and change in pure-tone average (PTA) differ by generation and identify factors underlying these differences. Design, Setting, and Participants: This cohort study used data from the Epidemiology of Hearing Loss Study (EHLS) and Beaver Dam Offspring Study (BOSS), a pair of studies of adults in Beaver Dam, Wisconsin. Baseline examinations occurred from 1993 to 1995 in the EHLS and 2005 to 2008 in BOSS, with two 5-year follow-up examinations in each cohort. This longitudinal cohort study assessed 3651 participants without HI at baseline who had follow-up data. Main Outcomes and Measures: The primary outcome was incident HI measured by pure-tone audiometry, defined as PTA greater than 25-dB hearing level (dB HL) in either ear. Associations of 5-year incidence were estimated by relative risks (RRs) and 10-year cumulative incidence with generation, as categorized by commonly used sociodemographic descriptors of year of birth, by hazard ratios (HRs). The 10-year change in PTA was investigated using a generation × time interaction term in generalized estimating equation models. Results: Among the 3651 participants (mean [SD] age at baseline 53.1 [10.6] years; 2255 [61.8%] female; and 3567 [97.7%] non-Hispanic White), the 5-year HI incidence was 14.1% (95% CI, 13.0%-15.3%) and the 10-year cumulative incidence was 26.0% (95% CI, 24.6%-27.6%). The incidence increased with age. The risk of 5-year incident HI decreased by generation (RR, 0.80; 95% CI, 0.66-0.97) when adjusting for multiple covariates. The decreased risk was similar in the 10-year period (HR, 0.86; 95% CI, 0.73-1.01). The PTA change rate (per 5 years of follow-up) decreased by generation, with the Greatest Generation (born 1901-1924) experiencing the highest rate (7.03 dB HL). The rates were all significantly lower for the other generations (Silent Generation [born 1925-1945], 3.30 dB HL; Baby Boom Generation [born 1946-1964], 3.36 dB HL; and Generation X [born 1965-1984], 2.33 dB HL). Conclusions and Relevance: This study suggests that the risk of HI and rate of PTA change is lower for the Silent Generation and Baby Boom Generation compared with the Greatest Generation. Part of this lower risk is likely associated with changes in modifiable factors. A potential continued benefit may exist for Generation X. Combined with the reduced risk of HI for the Silent Generation and Baby Boom Generation, this finding implies that the future HI burden may be lower than current estimates suggest.

The influence of the COVID-19 pandemic on traumatic brain injuries in Tyrol: experiences from a state under lockdown.

PURPOSE: In February 2020, the federal state of Tyrol in Austria has become one of the epicenters of the COVID-19 pandemic. Tyrol is known for numerous skiing areas. Thus, winter sport resorts became a starting point for COVID-19 infections spreading towards the rest of the state, Austria and other countries, leading to a mandatory quarantine for almost a million people, who were placed under a curfew and restrictions in daily life. Additionally, all ski resorts and hotels were closed. We aimed to analyze the influence of the COVID-19 quarantine on traumatic brain injury (TBI) cases in Tyrol. METHODS: We retrospectively compared demographical and injury characteristics from all TBI patients within the 2020 strict quarantine period with the respective time periods from 2016 to 2019. As our department is the only neurosurgical unit in Tyrol, all patients with moderate or severe TBI are transferred to our hospital. RESULTS: During 3 weeks of the full quarantine period, the weekly TBI cases load decreased significantly in comparison to the same time periods in the years 2016-2019. Furthermore, concomitant skull fractures decreased significantly (p < 0.016), probably reflecting different causative mechanisms. The other demographical and injury characteristics and particularly falls at home stayed relatively unchanged. CONCLUSION: TBI remained an important contributor to the neurosurgical workflow during the COVID-19 pandemic. Strategies to ensure neurosurgical care also under pandemic-induced lockdown are important.

13q deletion syndrome resulting from balanced chromosomal rearrangement in father: the significance of parental karyotyping.

BACKGROUND: Retinoblastoma is a malignancy of the eye in children characterized by biallelic inactivation of the retinoblastoma 1 gene (RB1), located at chromosome 13q14.2. Children with interstitial chromosome 13q deletions that include the RB1 gene show a predisposition to develop retinoblastoma and variable other features. Large 13q deletions with severe clinical phenotype are nearly always the result of a de novo mutation, i.e. the pathogenic alteration is not detected in parents. This results in a low risk for siblings to develop 13q deletion syndrome. RESULT: Here, we describe a patient with profound muscle hypotonia, severe developmental delay and bilateral retinoblastoma carrying a large deletion in 13q13.3q14 with the size of 16 Mb, involving the RB1 gene. Neither parent showed retinoblastoma, muscle hypotonia or developmental delay. Chromosome analysis and Fluorescence in situ hybridization (FISH) showed a balanced complex chromosomal rearrangement (CCR) between chromosome 12 and 13 [ins(12;13)(q21.2;q12.3q14.3)] and an additional balanced translocation of chromosome 7 and 15 [t(7;15)(q31.2;q25.3)] in the healthy father. Malsegregation of the paternal insertional translocation involving chromosome 12 and 13 resulted in a 13q deletion syndrome of the child [46,XY,ins(12;13)(q21.2;q12.3q14.3)]. CONCLUSION: Balanced translocations in parents are a rare cause of de novo RB1 deletions in offspring. This case report emphasizes the need for parental chromosomal analysis and FISH in parents of children diagnosed with 13q deletion syndrome or large RB1 gene deletions to precisely determine the recurrence risk in siblings. Guidelines for genetic testing should be revised accordingly.

The Contribution of Ototoxic Medications to Hearing Loss Among Older Adults.

BACKGROUND: Ototoxicity may interact with the effects of aging, leading to a more severe hearing loss than that associated with age alone. The purpose of this study was to explore the associations between ototoxic medication use and the incidence and progression of hearing loss in older adults with a population-based longitudinal study. METHODS: Epidemiology of Hearing Loss Study participants (n = 3,753) were examined. Medication use was assessed using a standardized questionnaire by the examiners at each examination every 5 year. The ototoxic medications include loop diuretics, nonsteroidal anti-inflammatory drugs, antibiotics, chemotherapeutic agents, quinine, and acetaminophen in this study. Generalized estimating equations model was used as a proportional hazard discrete time analysis. RESULTS: Number of ototoxic medications was associated with the risk of developing hearing loss during the 10-year follow-up period (hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.06, 1.25) after adjusting for age, sex, smoking, and body mass index. Loop diuretics (HR = 1.40, 95% CI = 1.05, 1.87) were associated with the 10-year incidence of hearing loss. Nonsteroidal anti-inflammatory drugs (HR = 1.45, 95% CI = 1.22, 1.72) and loop diuretics (HR = 1.33 95% CI = 1.08, 1.63) were associated with risk of progressive hearing loss over 10 years. CONCLUSION: These ototoxic medications are commonly used in older adults and should be considered as potentially modifiable contributors to the incidence and severity of age-related hearing loss.

Severe pressure ulcers requiring surgery impair the functional outcome after acute spinal cord injury.

STUDY DESIGN: Retrospective matched cohort study. OBJECTIVES: Assessing the influence of surgically managed grade 3 and 4 pressure ulcers (PU) in the acute phase after spinal cord injury (SCI) on the neurological and functional outcome after 1 year. SETTING: Specialized SCI-unit within a level 1 trauma center in Murnau, Germany. METHODS: We performed a retrospective matched cohort study. For every patient with acute SCI and a PU requiring surgery, we identified matched controls within our database in a 1:3 ratio. Matching criteria were: AIS-grade (American Spinal Injury Association Impairment Scale), neurological level and age. The scores of the SCIM-III (Spinal Cord Independence Measure) and the ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) as well as the total length of stay (LOS) at the hospital were used as outcome parameters. We applied a stratified analysis using a conditional logistic regression to test for group differences in each outcome parameter of the study. RESULTS: In a 6-year period (2010-2015) 28 patients required flap surgery due to 3-4° PU in the acute phase after SCI. Of these patients, 15 had complete data sets according to the EMSCI (European Multicenter Study about Spinal Cord Injury) protocol. Patients with severe PUs during the acute SCI phase had a significantly impaired functional outcome. After 1 year the improvement of the SCIM score was significantly lower in the PU group compared to the control group (17.4 versus 30.5; p < 0.006). However, the change in AIS grade after 1 year was not significantly affected. The LOS was prolonged by a mean of 48 days in the PU group (p < 0.006). CONCLUSIONS: Severe PUs requiring surgery in the acute phase after SCI impair the functional outcome and increase LOS. Preventive measures should be applied to all acute SCI patients. Patients should be transferred to specialized SCI-centers as soon as possible.

Cadmium, obesity, and education, and the 10-year incidence of hearing impairment: The beaver dam offspring study.

OBJECTIVES/HYPOTHESIS: To determine the 10-year incidence of hearing impairment (HI) and associated risk factors in the Beaver Dam Offspring Study (BOSS; 2004-present), a large middle-aged cohort followed for 10 years. STUDY DESIGN: Prospective cohort study. METHODS: Hearing thresholds were measured at baseline (2005-2008) and 5- (2010-2013) and 10-year (2015-2017) follow-up examinations. HI was defined as a pure-tone average >25 dB HL in either ear. BOSS participants free of HI at baseline with at least one follow-up examination (N = 2,065) were included. Potential risk factors evaluated included cardiovascular measures, health history, lifestyle factors, inflammatory markers, vitamins D and B12, lead, and cadmium. RESULTS: Participants were 21 to 79 years (mean age = 47.9 years) at baseline. The 10-year cumulative HI incidence was 17.4% (95% confidence interval [CI]: 15.7-19.2) and was twice as likely in men (24.4%, 95% CI: 21.5-27.7) than in women (12.2%, 95% CI: 10.3-14.3). In a multivariable adjusted model, age (hazard ratio [HR] = 1.48, 95% CI: 1.38-1.59, per 5 years), male sex (HR = 2.47, 95% CI: 1.91-3.18), less than a college education (HR = 1.35, 95% CI: 1.02-1.79), body mass index (HR = 1.03, 95% CI: 1.01-1.05, per kg/m2 ), and higher cadmium levels (HR = 1.42, 95% CI: 1.05-1.92, quintile 5 vs. quintiles 1-4) were associated with the 10-year cumulative incidence of HI. There was no association between high lead levels, vitamins D or B12, and 10-year incidence of HI. CONCLUSIONS: In addition to age and sex, obesity, education, and blood cadmium levels were associated with increased incidence of HI. These prospective results add to evidence that age-related HI is a multifactorial preventable disorder. LEVEL OF EVIDENCE: 2b Laryngoscope, 130:1396-1401, 2020.

Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly. OBJECTIVE: This study aimed to determine the association between dietary patterns and food groups (used to make them) with the 18-year incidence of AMD. METHODS: ARIC (Atherosclerosis Risk in Communities) participants who showed change in AMD lesions between retinal photographs taken at visit 3 and visit 5 were graded side by side to determine incident AMD (any=144; early=117; late=27). A 66-line item food frequency questionnaire, administered at visit 1 and visit 3, was used to identify 29 food groups. Principal component analysis was used to derive dietary patterns from average food group servings. Logistic regression was used to estimate ORs and 95% CIs for incident AMD (any, early and late) by tertiles of dietary pattern scores, adjusted for age, race, education, total calories and smoking status. P-trend was estimated using continuous scores. RESULTS: Western (unhealthy) and Prudent (healthy) dietary patterns were identified. No significant associations were observed between either dietary pattern and incident any or incident early AMD. However, a threefold higher incidence of late AMD was observed among participants with a Western pattern score above, as compared with below, the median (OR=3.44 (95% CI 1.33 to 8.87), p-trend=0.014). The risk of developing late AMD was decreased, but not statistically significant, among participants with a Prudent pattern score above, as compared with below, the median (OR=0.51 (95% CI 0.22 to 1.18), p-trend=0.054). CONCLUSIONS: Diet patterns were not significantly associated with incident any or incident early AMD. However, consumption of a Western pattern diet may be a risk factor for development of late AMD.

Central arterial stiffness and retinal vessel calibers: the Atherosclerosis Risk in Communities Study-Neurocognitive Study.

BACKGROUND: The retinal microvasculature provides a window to the cerebral vasculature and enables examination of changes in retinal caliber that may mimic those occurring in cerebrovascular disease. The association of central arterial stiffness and retinal vessel caliber in a population sample is not fully understood. METHODS: In 1706 older adults (mean age 76.3, 58.1% women) from the population-based Atherosclerosis Risk in Communities Study, we examined the cross-sectional association of central arterial stiffness [carotid-femoral pulse wave velocity (cfPWV)] with retinal vessel calibers [central retinal arteriolar equivalent (CRAE) and central retinal vein equivalent (CRVE)]. We estimated the association of cfPWV with CRAE narrowing (<25th percentile) and CRVE widening (>75th percentile) after adjustment for age, sex, race-field center, BMI, smoking, and type 2 diabetes. We tested for effect modification by sex, hypertension, and type 2 diabetes. RESULTS: Carotid-femoral PWV (m/s) was not associated with the odds of CRAE narrowing [odds ratio (OR): 0.99; 95% CI: 0.95-1.03]. The association of cfPWV with CRVE widening was stronger in those without hypertension (OR: 1.10; 95% CI: 1.01-1.20) versus those with hypertension (OR: 1.01 95% CI: 0.96-1.05) and slightly stronger in those with type 2 diabetes (OR: 1.07; 95% CI: 1.00-1.14) versus without type 2 diabetes (OR: 1.01; 95% CI: 0.96-1.06). CONCLUSIONS: In older adults, cfPWV was associated with wider retinal venular caliber, particularly in individuals without hypertension. Central arterial stiffening may be associated with cerebral microvascular changes, as exhibited in its retinal vasculature component.

Early Decompression (<8 Hours) Improves Functional Bladder Outcome and Mobility After Traumatic Thoracic Spinal Cord Injury.

BACKGROUND: There is accumulating evidence of a potential beneficial effect of early surgical intervention after acute cervical spinal cord injury (SCI). However, around one third of all SCIs affect the thoracic spine. This cohort has not been extensively investigated, mainly because of less sensitive clinical readout measures. Apart from regaining full sensorimotor function, improvements in bladder and bowel management remain of the highest priority for patients with chronic paraplegia. Therefore, this study investigates the effect of early decompression (here defined as <8 hours) versus delayed management on neurologic and functional outcome. METHODS: We retrospectively analyzed data from the institutional database, in which follow-up data were collected prospectively according to the European Multicenter Study about Spinal Cord Injury standards. Within a 13-year period, we identified 43 patients who met inclusion and exclusion criteria. Of these, 32 (74%) were managed surgically within the first 8 hours. There was a trend toward a higher rate of patients with clinically complete SCI in the early group at baseline. RESULTS: After 1 year, we did not observe a benefit on the neurologic outcome as assessed via the American Spinal Injury Association Impairment Scale grade. Functional outcome was evaluated using the Spinal Cord Independence Measure (SCIM). The early decompressed group demonstrated significantly improved SCIM 6 (i.e., bladder management) (P < 0.045) and SCIM 9-11 subitems (i.e., mobility, transfer) (P < 0.019). CONCLUSIONS: Early decompression was an independent predictor for improved functional bladder outcome and mobility after 1 year. This effect needs to be studied in future prospective, multicenter studies.

An Association Between Large Optic Nerve Cupping and Cognitive Function.

PURPOSE: To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension. METHODS: We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy. RESULTS: Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04). CONCLUSIONS: Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Serum 25-Hydroxyvitamin D Concentrations and Incidence of Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study.

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentrations at visit 2 (1990-1992) and the 18-year incidence of age-related macular degeneration (AMD) between visit 3 (1993-1995) and visit 5 (2011-2013). Methods: This prospective analysis was conducted in a subset of participants (n = 1225) from the Atherosclerosis Risk in Communities Study. We evaluated the incidence of any, early, and late AMD from visit 3 to 5. The 25(OH)D concentrations were assessed in 2012-2013 by using stored serum from visit 2. Retinal fundus photographs taken at both visits were graded side by side to determine the incidence of AMD. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for incident AMD outcomes during 18 years of follow-up (1993-1995 to 2011-2013) by tertile of 25(OH)D adjusted for age, race, and smoking status. P for linear trend was estimated by using continuous 25(OH)D concentrations. Sensitivity analyses applied inverse probability weights to account for selection to have eye photographs, death, and loss to follow-up. Results: There was a decreased odds of any incident AMD (n = 139) and large, soft drusen (n = 80) in 25(OH)D tertile 3 versus 1, with OR (95% CI) = 0.57 (0.36-0.90), P trend = 0.11 and with 0.52 (0.28-0.93), P trend = 0.18, respectively. Applying sampling weights attenuated these results to 0.66 (0.38-1.16), P trend = 0.32 (any incident AMD) and 0.54 (0.27-1.09), P trend = 0.36 (large, soft drusen), respectively, suggesting these associations may be biased by loss to follow-up and sampling for retinal photographs at visit 5. No statistically significant results were observed with pigmentary abnormalities (n = 46) or incident late AMD (n = 26). Conclusions: High 25(OH)D concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD.

Brain Aging in Midlife: The Beaver Dam Offspring Study.

OBJECTIVES: Middle age has been identified as a critical time period for health later in life. Identifying factors associated with worse brain function in middle-aged adults may help identify ways to preserve brain function with aging. Our objective was to evaluate factors associated with a novel measure of brain aging in middle-aged and older adults. DESIGN: Longitudinal cohort study. SETTING: Beaver Dam Offspring Study (BOSS) baseline (2005-2008), 5-year (2010-2013), and 10-year examinations (2015-2017). PARTICIPANTS: A total of 2285 adults, 22 to 84 years of age, with complete sensorineural and neurocognitive data at the 5-year examination. MEASUREMENTS: Principal component analysis (PCA) was performed combining 5-year sensorineural (hearing, vision, olfaction) and cognitive (Trail Making Test A and B, Digit Symbol Substitution Test, Verbal Fluency Test, Auditory Verbal Learning Test) test data. Participants with a standardized PCA score less than -1 were classified as having brain aging. Incident brain aging was defined as a PCA score less than -1 at 10 years among participants who had a PCA score of -1 or higher at 5 years. Logistic regression and Poisson models were used to estimate associations between baseline factors and prevalent or incident brain aging, respectively. RESULTS: Older age, being male, current smoking, larger waist circumference, not consuming alcohol, cardiovascular disease, and interleukin-6 were associated with greater odds of prevalent brain aging, whereas more education and exercise were associated with decreased odds. In addition to age and sex, less than a college education, higher levels of soluble intercellular adhesion molecule-1, diabetes, depressive symptoms, and history of head injury were associated with an increased 5-year risk of incident brain aging. CONCLUSION: In the current study, vascular and inflammatory factors were associated with a new brain aging marker in middle-aged and older adults. Many of these factors are modifiable, highlighting the importance of addressing health and lifestyle factors in midlife to potentially preserve function for better brain health later in life. J Am Geriatr Soc 67:1610-1616, 2019.

Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium.

OBJECTIVE: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN: Individual participant data meta-analysis. SETTING: Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

Sensorineural Impairments, Cardiovascular Risk Factors, and 10-Year Incidence of Cognitive Impairment and Decline in Midlife: The Beaver Dam Offspring Study.

BACKGROUND: Sensorineural impairments and cardiovascular risk factors (CVRF) and disease (CVD) in midlife may be important predictors of future cognitive health, but longitudinal studies that include multiple sensorineural measures in middle-aged adults are lacking. METHODS: Hearing, vision, and olfaction, and CVRF and CVD were measured at the Beaver Dam Offspring Study baseline (2005-2008) examination. The Mini-Mental State Examination and Trail Making Tests A and B were administered at all phases and additional cognitive function measures were obtained at 5 (2010-2013) and 10 years (2015-2017). Cox proportional hazards models were used to evaluate associations between baseline sensorineural impairments, CVRF, CVD, and 10-year cumulative incidence of cognitive impairment and decline. RESULTS: There were 2,556 participants (22-84 years) without cognitive impairment at baseline and data from at least one follow-up. In a multivariable model including age, sex, education, and head injury, visual impairment (hazard ratio = 2.59, 95% confidence interval = 1.34, 5.02), olfactory impairment (hazard ratio = 3.18, 95% confidence interval = 1.53, 6.59), CVD (hazard ratio = 2.37, 95% confidence interval = 1.24, 4.52), and not consuming alcohol in the past year (hazard ratio = 2.21, 95% confidence interval = 1.16, 4.19) were associated with the 10-year cumulative incidence of cognitive impairment. Current smoking and diabetes were associated with increased risk, and exercise with decreased risk, of 10-year decline in cognitive function. CONCLUSIONS: Visual and olfactory impairments, CVRF, and CVD were associated with the 10-year cumulative incidence of cognitive impairment and decline in middle-aged adults. Identifying modifiable factors associated with cognitive decline and impairment in midlife may provide opportunities for prevention or treatment and improve cognitive health later in life.