Biomarcadores de enfermedad de Alzheimer en deterioro cognitivo leve: experiencia en una clínica de memoria de Latinoamérica / Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a memory clinic from Latin America

Objetivo: El objetivo de este estudio fue investigar el rol y pronóstico de los biomarcadores de enfermedad de Alzheimer en pacientes con diagnóstico clínico de deterioro cognitivo leve (DCL) en una clínica de memoria de Latinoamérica.MétodoOchenta y nueve pacientes con DCL, 43 con demencia tipo Alzheimer y 18 controles normales apareados por edad, sexo y escolaridad fueron estudiados con un extenso protocolo demográfico, neurológico y neuropsicológico en la clínica de memoria del Instituto FLENI de Buenos Aires. Todos completaron una RM cerebral, una PET con FDG, una PET con estudios amiloideo (PIB), genotipificación de APOE y estudio de Aβ1-42, tau and f-tau de líquido cefalorraquídeo. Basado en la presencia/ausencia de patología amiloidea y neurodegeneración los pacientes fueron categorizados como A+/A− y N+/N− respectivamente.ResultadosEn el estudio de líquido cefalorraquídeo el 18% de los controles, el 64% de los DCL y el 92% de las demencia tipo Alzheimer tenían patología amiloidea; y un 11% de los controles, el 6% de los DCL y el 8% de las DTA eran sospechosos de fisiopatología no Alzheimer. En el seguimiento a los 30 meses el 45% de los DCL con amiloide positivo y el 20% de los que presentaron amiloide negativo progresaron a demencia.ConclusionesEste estudio muestra el pronóstico de los DCL basado en los biomarcadores, y respalda su importancia en la toma de decisiones en la práctica diaria. (AU)

Objective: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America.MethodsWe studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aβ1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration.ResultsAmyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non–Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia.ConclusionsThis study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice. (AU)

Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a memory clinic from Latin America. / Biomarcadores de enfermedad de Alzheimer en deterioro cognitivo leve: experiencia en una clínica de memoria de Latinoamérica.

OBJECTIVE: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. METHODS: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aß1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. RESULTS: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non-Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. CONCLUSIONS: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice.

Prediction of Gait without Physical Assistance after Inpatient Rehabilitation in Severe Subacute Stroke Subjects.

BACKGROUND: Gait recovery is one of the main therapeutic goals of the rehabilitation for patients after a stroke. OBJECTIVE: This study is aimed at describing the frequency of achievement of gait without physical assistance in poststroke subacute patients by the time of discharge from a rehabilitation hospitalized program. Secondarily, our goal is to identify gait without physical assistance predictors in this same population based on the admission's clinical and demographic conditions. METHODS: Data from 185 first unilateral hemispheric stroke patients that need physical assistance to walk at admission were analyzed. The sample was dichotomized into gait with physical assistance and gait without physical assistance to calculate the frequency of achievement of gait without assistance at discharge. Multivariate logistic modeling was applied to identify prognostic factors for regaining gait without physical assistance. RESULTS: Gait without assistance was achieved in 50.27% of the subjects. Five variables were identified for the prediction model: age (Odds ratio [OR] = .87, 95% confidence interval [CI] = .83-.92), gender (OR = .37, 95% CI = .14-.94), time between stroke and hospitalization (OR = .96, 95% CI = .94-.99), initial Berg Balance (OR = 1.52, 95% CI = 1.23-1.88), and initial lower limb Fugl Meyer (OR = 1.17, 95% CI = 1.07-1.27). CONCLUSIONS: Although discharge planning is complex, achievement of gait without physical assistance is undoubtedly a landmark to decide on hospitalization discharge. Half of this sample was able to walk without physical assistance at hospitalization discharge. Five clinical and demographic conditions at admission were found predictors of gait without physical assistance at inpatient discharge.

National Trends and Outcomes of Patients Bridged to Transplant With Continuous Flow Left Ventricular Assist Devices.

BACKGROUND: Continuous flow left ventricular assist devices (CF-LVAD) are widely used as a bridge to transplantation (BTT) among patients with advanced heart failure. The primary outcome of the current study was to study the incidence of waitlist mortality and morbidity of CF-LVAD patients bridged to heart transplantation in the current BTT era and to determine the factors that increased their risk of delisting. METHODS: Patients who were bridged to heart transplant with a CF-LVAD between April 2008 and September 2015 were identified from the United Network for Organ Sharing heart transplant registry. They were then categorized based on the development of complications. Cox proportional hazards and Kaplan-Meier survival curves were used for time-to-event analysis for the primary outcome. RESULTS: Out of 7070 patients who were bridged to heart transplant, 2510 (36%) developed device-related complications. The primary outcome was present in 1631 of 7070 patients (23%). Independent predictors of primary outcome were age, ABO blood group, etiology of cardiomyopathy, and history of diabetes mellitus. Developing one device-related complication was associated with a hazard ratio (HR) of 2.59 of having the primary outcome. The HR increased to 3.45 when ≥2 of the defined complications occurred. In patients who developed the primary outcome, they most likely had a device infection (odds ratio 2.51). CONCLUSION: Findings from the current study add to the existing literature about the incidence of morbidity and mortality in the current BTT era. Development of one device-related complication increases the risk of death or delisting among patients on the heart transplant waitlist; however, this risk almost doubles when 2 or more complications occur.

Impact of Baseline Mitral Regurgitation on Postoperative Outcomes After Left Ventricular Assist Device Implantation as Destination Therapy.

BACKGROUND: Currently, there are no guidelines for management of moderate to severe mitral regurgitation (MR) in patients undergoing left ventricular assist device (LVAD) implantation. The present study aimed to investigate the impact of baseline MR on short and midterm survival in patients who had LVAD as destination therapy (DT). METHODS: The DT-LVAD patients were classified into 2 groups based on baseline MR status: ≥ moderate MR and < moderate MR. Baseline clinical characteristics and post-LVAD implant adverse events were compared. Unadjusted mortality rates at 30 days, 1 year, and 2 years were analyzed. RESULTS: Of 91 patients studied, 62 (68%) had ≥ moderate MR before LVAD implantation; ≥ moderate MR patients had a higher incidence of concomitant pulmonary disease (11% vs 0%; P = .001) and ≥ moderate tricuspid regurgitation (55% vs 23%, P = .004) than < moderate MR patients. Other baseline clinical characteristics were similar in both groups. Post-LVAD adverse events did not differ between the 2 groups. Survival rates at 30 days, 1 year, and 2 years for both groups (≥ moderate MR vs < moderate MR) were 90% vs 100% (P = .03), 63% vs 90% (P = .001), and 52% vs 83% (P = .002), respectively. On multivariable analysis, age, female sex, ≥ moderate tricuspid regurgitation, and ≥ moderate MR at baseline were found to be independent predictors of overall all-cause mortality. Overall survival was significantly lower in the ≥ moderate MR group than the < moderate MR group (log-rank test, P = .03). CONCLUSION: In DT LVAD patients, ≥ moderate MR is common and is associated with worse survival at both short and midterm follow-up.

Abusive early child rearing and early childhood aggression.

Childhood aggression is significant for children, their families, and the society because aggressive children often become violent adolescents. This article examines the relationship between maltreatment and early childhood aggression. Data are from a longitudinal study of maltreated and nonmaltreated children assessed as preschoolers and again at school age. The dependent variable is the child's teacher's rating of aggression at school age. The independent variables are from preschool and school age observations of the mother-child interaction and the mother's report of physical discipline practices. Using structural equation modeling, harshness of interaction at preschool age but not school age and severity of physical discipline at school age but not preschool age, relate to aggression at school age. Results suggest a difference in the developmental stage at which different features of harsh child rearing exert their influence. Strategies for intervening to prevent the development of childhood aggression are suggested.

Intracellular trehalose improves the survival of cryopreserved mammalian cells.

We report that the introduction of low concentrations of intracellular trehalose can greatly improve the survival of mammalian cells during cryopreservation. Using a genetically engineered mutant of Staphylococcus aureus alpha-hemolysin to create pores in the cellular membrane, we were able to load trehalose into cells. Low concentrations (0.2 M) of trehalose permitted long-term post-thaw survival of more than 80% of 3T3 fibroblasts and 70% of human keratinocytes. These results indicate that simplified and widely applicable freezing protocols may be possible using sugars as intracellular cryoprotective additives.

Increase in admission threshold explains stable asthma hospitalization rates.

BACKGROUND: Asthma morbidity and mortality has increased substantially in recent years, but asthma hospitalization rates among many geographic and sociodemographic groups have remained stable. Observations on asthma hospitalization rates and severity of acute episodes might provide valuable insight into the functioning of the health care system during this period of health care reform. OBJECTIVE: To analyze changes between 1991 and 1995 in childhood asthma hospitalization rates and severity of acute episodes. DESIGN AND METHODS: All 29 329 hospitalizations, including 2028 for asthma, for the 198 893 children (<19 years of age) in Monroe County (Rochester), New York, were studied during this 5-year period. Severity was determined by hospital record review on a 22% random sample. Using the worst oxygen saturation (SaO(2)) during the first 24 hours of hospitalization as the primary index of severity, episodes were categorized as mild (0 to >/=95), moderate (90 to 94), or severe (<90). RESULTS: Hospitalization rates are expressed as hospitalizations per 1000 child-years. The overall asthma hospitalization rate was 2.04 (95% confidence interval, 1.95-2.13). The overall annual asthma hospitalization rate remained relatively stable from 1991 (1.90) to 1995 (2.31), whereas the hospitalization rates for severe asthma rose 270%-from 0.57 to 1.55-during this period. Simultaneously, the hospitalization rates for mild asthma decreased from 0.26 to 0.12. As a proportion of all asthma hospitalizations between 1991 and 1995, severe episodes increased from 31.5% to 60.4%; conversely, mild episodes decreased from 14.1% to 4.7%. CONCLUSIONS: Severity increased significantly among children hospitalized for asthma while the overall asthma hospitalization rate remained stable. It seems that the health care system in this community has responded to an increase in severity of asthma by raising the severity threshold for admission.

Socioeconomic variation in asthma hospitalization: excess utilization or greater need?

OBJECTIVE: To assess the hypothesis that higher incidence of severe acute asthma exacerbation, not lower severity threshold for admission, explains the difference between the asthma hospitalization rates of inner-city and suburban children. METHODS: All 2028 asthma hospitalizations between 1991 and 1995 for children (aged >1 month and <19 years) dwelling in Rochester, New York, were analyzed. ZIP codes defined residences as inner-city, other urban, or suburban. Based principally on the worst oxygen saturation (SaO2) during the first 24 hours of hospitalization, severity was examined by hospital record review (n = 443) of random samples of inner-city, other urban, and suburban asthma admissions. RESULTS: Large inner-city/suburban differences were noted in many sociodemographic attributes, and there was also a distinct, stepwise gradient in risk factors in moving from the suburbs to other urban areas and to the inner city. Racial and economic segregation was particularly striking. Black individuals accounted for 62% of inner-city births versus <3% in the suburbs. Medicaid covered 65% of inner-city births, whereas Medicaid covered only 6% of suburban births. The overall asthma hospitalization rate was 2.04 admissions/1000 child-years. Children <24 months old, those most commonly hospitalized for asthma, were fourfold more likely to be hospitalized (OR: 3.97, 95% CI: 3. 44-4.57) than children between the ages of 13 and 18 years. The hospitalization rate of asthma in boys was almost twice the rate of asthma in girls. The greatest gender difference was observed among children who were <24 months old. For these children, the rate for boys was 6.10/1000 child-years compared with 2.65/1000 child-years for girls (OR: 2.31, 95% CI: 1.95-3.03). This gender difference diminished gradually in older age groups to the extent that there was no difference among girls and boys between the ages of 13 and 18 years (males, 1.12/1000 child-years vs females, 1.09/1000 child-years). Based on worst SaO2 values, mild (worst SaO2 >/=95%), moderate (90%-94%), and severe (<90%) admissions constituted 10.3%, 41.9%, and 47.7% of all hospitalizations, respectively. Although rates within the community followed a distinct geographic pattern of suburban (1.05/1000 child-years) < other urban (2.99/1000 child-years) < inner-city (5.21/1000 child-years), the proportions of admissions with low severity did not vary among areas. Likewise, the proportions of admissions that were severe (SaO2 <90%) were not significantly different (44.8, 45.7, and 52.1% for suburban, other urban, and inner-city areas, respectively). The distributions of asthma severity, measured by the duration of frequent nebulized bronchodilator treatments and the length of hospital stay, were also similar among children from different socioeconomic areas. CONCLUSION: The marked socioeconomic and racial disparity in Rochester's asthma hospitalization rates is largely attributable to higher incidence of severe acute asthma exacerbations among inner-city children; it signals greater need, not excess utilization. Both adverse environmental conditions and lower quality primary care might explain the higher incidence. Interventions directed at the environment offer the possibility of primary prevention, whereas primary care directed at asthma is focused on secondary prevention, principally on improved medication use. Higher hospitalization rates cannot be assumed to identify opportunities for cost reduction. The extent to which our observations about asthma hold true under other conditions and in other communities warrants systematic attention. Knowledge of when higher rates signal excess utilization and when, instead, they signify greater needs should guide equitable national health policy.

How commonly are children hospitalized for asthma eligible for care in alternative settings?

OBJECTIVE: To estimate the proportion of children hospitalized for acute asthma exacerbation who might be cared for successfully in alternative settings such as short-stay units or in-home nursing. DESIGN: Descriptive study based on analysis of hospital discharge files and on retrospective medical record review of a random sample of asthma hospitalizations. METHODS: The 2028 asthma hospitalizations between 1991 and 1995 for children (aged <19 years) dwelling in Rochester, NY, were studied. Measures included the duration of frequent administration of nebulized medication (2 or more times in a 4-hour period), worst oxygen saturation levels, deterioration, and hospital length of stay. Oxygen saturation values and nebulized medication frequency were determined by hospital record review on a random sample of 443 asthma episodes. Length of stay was available for all admissions. RESULTS: Worst oxygen saturation following hospital admission was 95% or greater, 90% to 94%, and less than 90% for 21.3%, 51.6%, and 27.1% of episodes, respectively. Children received frequent nebulized medication treatments for a mean of 2.0 nursing shifts (8 hours per shift), although they remained hospitalized, on average, for 4.3 nursing shifts longer. Deterioration to a critical level of severity was uncommon. Among children initially admitted to the regular pediatric inpatient unit, only 0.7% subsequently deteriorated to the point that they were transferred to the critical care unit. CONCLUSION: More than 70% of asthma hospitalizations in this community could be cared for in alternative settings with supplemental oxygen, nebulized medication treatments, and close nursing observation provided, in most cases, for 2 nursing shifts.

Cryopreservation of rat hepatocytes in a three-dimensional culture configuration using a controlled-rate freezing device.

From engineered tissues to transfected cell lines, the long term storage of living biologicals is desirable for a variety of medical, scientific, economic, and regulatory concerns, including transport, the expense of development, repeatability issues, and the point of use. Currently, the best option is cryogenic storage, placing the biomaterials in suspended animation at very low temperatures (-196°C), halting all chemical reactions, limiting genetic drift, and ensuring the maintenance of cell viability and function upon thawing (1). Obtaining such an advantageous state, however, can be a difficult achievement. This problem becomes further complicated as we move toward next generation multicomponent products such as engineered skin and cartilage substitutes, composed of multiple cell types oriented in complicated three-dimensional geometries within an extracellular matrix scaffold (2-4).

The relationship between early maltreatment and teenage parenthood.

In a longitudinal study of the effects of early childhood maltreatment, 92 adolescents who had become parents while under 20 years of age were compared to 297 adolescents who had not become parents during their teenage years. Preschool and school-age physical abuse alone and in combination with neglect were found to have significant relationships with teenage parenthood. Low self-esteem, as evaluated by elementary school teachers, was related to both early maltreatment and teenage parenthood. Sexual abuse, based on retrospective reports of the adolescents, had a significant but weaker relationship to teenage parenthood. The implications of these findings and the findings that high school dropout, assaultive behavior, and drug use are also related to teenage parenthood are discussed.

Reversible permeabilization of plasma membranes with an engineered switchable pore.

By using an engineered, self-assembling, proteinaceous, 2-nm pore equipped with a metal-actuated switch, a technique to reversibly permeabilize the plasma membrane to small molecules (approximately 1000 Da) has been developed. We have demonstrated the dose-dependent permeabilization of fibroblasts by pores designed to be blocked and unblocked by the addition and removal of microM concentrations of Zn2+. Further, we have shown that the activity of the switch allows permeabilized cells to maintain viability and ultrastructural integrity following the unconstrained flux of small molecules. This ability to control the transmembrane influx and efflux of molecules and thereby vary the intracellular environment yet maintain cell viability will impact an array of biological and medical problems.