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Paediatric sepsis remains an important cause of morbidity and mortality in children. This review will summarize the main aspects of the definition, current evidence-base for interventions and suggest possible areas of improvement. Controversy remains regarding accurate definitions for paediatric sepsis, resuscitation fluid volume and type, choice of vasoactive agents for use in resuscitation and antibiotic choices. Many adjunctive therapies have been suggested with theoretical benefit, although few have proven beneficial. Definitive recommendations are not yet supported by data. We describe best practice recommendations based on international guidelines, a review of primary literature, and a discussion of ongoing clinical trials and the nuances of therapeutic choices. Early diagnosis and aggressive intervention with timely antibiotics, fluid resuscitation and vasoactive medications are the most important interventions in to improve outcomes. The implementation of protocols, resource-adjusted sepsis bundles and advanced technologies will impact on reducing sepsis mortality. [ABSTRACT FROM AUTHOR]

Background: New technologies have helped the biological diagnosis of Alzheimer's disease to make it more accurate over the years. However, establishing prognosis for each case is still a significant challenge, as there are different cognitive profiles in the same diagnosis. Also, there is no well‐defined standard for a cognitive profile that predicts future functionality impairment. In this sense, a better understanding of cognitive phenotypes can help establishing prognosis of Alzheimer's dementia. Our aim with this study was to identify the main cognitive profiles of patients with amnestic variant of probable Alzheimer's dementia at a mild presentation (CDR 1) with the amnestic variant. We verified the performance of these cognitive profiles applying the neuropsychological assessment. Method: The study comprised 141 participants with probable Alzheimer dementia, recruited from a Reference Center for the Elderly in Brazil. We conducted a complete neuropsychological assessment evaluating the following domains: memory, executive functions, language, simple attention/processing speed, and visuospatial abilities. Initially, the data were transformed in z‐scores, considering age and education, according to references for the cultural adaptations and validations for the Brazilian population. We use the K‐Nearest Neighbors (K = 3) to solve the missing data problem. After preparing the base for cluster analysis, we performed the ward's hierarchical method and the Euclidean distance to measure similarity. Finally, we performed comparisons of the groups using the Kruskal‐Wallis tests. Result: Data analysis suggested existence of five cognitive subgroups (Figure 1). Bye general comparison, performed by the Kruskal‐Wallis test, we found the groups were different in the neuropsychological assessment instruments (p<0.001). Cognitive phenotypes varied about impaired and/or preserved ability, as well as impairment severity (Figure 2). The cognitive phenotypes were different considering educational level (Figure 3). We observed accentuated global impairment cognitive phenotype in a lower level of formal education group, and less accentuated impairment profiles in a higher formal education. Conclusion: In conclusion, we identified five Cognitive phenotypes which had differences in severity of cognitive symptoms, and impaired abilities. These Cognitive phenotypes were based on different degrees of severity in visuospatial ability, simple attention/processing speed, and planning and had different education level. [ABSTRACT FROM AUTHOR]

Background: The incidence and prevalence of dementia are increasing, mainly in low‐ and middle‐income countries. Alzheimer's disease (AD) accounts for the majority of cases. Thus, cost‐effective techniques with lower cost are necessary for scaling up the number of tested individuals in these countries for research and clinical use. Luminex (Millipore xMap®) is a semi‐automated test that can analyze CSF biomarkers with a cost per sample of one fourth of ELISA's kits. Method: We performed a cross‐sectional, case‐control study. After consent, 35 older adults were submitted to clinical and neuropsychological assessment, and then to a lumbar puncture. Based on clinical and neuropsychological assessment, seven patients had a diagnosis of AD's dementia (McKhann criteria), 17 of amnestic mild cognitive impairment (MCI) (DSM‐5 criteria) and 11 without objective cognitive impairment. CSF biomarkers concentrations were measured by INNOTEST® (ELISA) and Millipore xMap®. Both techniques were compared and the accuracy of the latter was assessed. Result: Millipore xMap® measurements showed a robust accuracy for all biomarkers, with AUC of 0.808 for t‐Tau, 0.935 for p‐Tau and 0.952 for Aβ42 compared to ELISA as the reference test. The Aβ42 showed a great sensibility (100%) and the ratio p‐tau/Aβ42 a good specificity (0,944). So, we propose a stepwise approach for the diagnosis of AD based on CSF biomarkers. A patient with a cognitive assessment suggestive of AD (MCI or initial dementia) could be initially assessed for CSF biomarkers with a more affordable test, such as Luminex. If there is a need of a confirmation due low pretest probability or the need of a more specific test for a high‐cost treatment, researchers and clinicians could order an ELISA test in the same CSF sample or additional molecular neuroimaging techniques. For patients with a high pretest probability, Luminex has excellent accuracy and can define biological diagnosis. Conclusion: The use of Millipore xMap® as the first step in a stepwise approach for the assessment of suspected AD in middle‐ and low‐income countries cases is promising, considering its accuracy and lower cost per sample. Still, the implementation of the proposed approach in this study should be replicated in larger and different samples. [ABSTRACT FROM AUTHOR]

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Background: Comparison between functionality and cognition in elderly patients with Alzheimer’s dementia (AD) and without cognitive impairment with positive and negative Aβ‐42 and p‐Tau biomarkers evaluated using the Luminex technique. Method: Patients with Alzheimer’s dementia and normal cognition (control) were recruited. They were divided in two groups according to their clinical diagnosis: AD group (n=30) and control group (CTRL) (n=10). The AD group was then divided in patients with positive (n=21) and negative (n=9) Aβ‐42 and p‐Tau biomarkers. The participants were submitted to sociodemographic. The general cognition was evaluated through the following instruments: the Mini‐Mental State Examination (MMSE), semantic verbal fluency (SVF), animal fluency, short term memory, and recognition of CERAD battery, and functionality was evaluated by the Pfeffer scale. Samples from the cerebrospinal fluid (CSF) of patients were collected, processed, and stored at ‐80°C until use. The Luminex technique was then used for the Aβ‐42, t‐Tau, p‐Tau, t‐Tau/Aβ‐42 ratio, and p‐Tau/Aβ‐42 ratio biomarker analysis. Obtained data was processed and analyzed through the software SPSS 22.0. Result: Comparison between control patients and patients with AD, as defined by clinical diagnosis, did not show significant differences regarding to Aβ‐42 expression in CSF (U=91,000; p=0,067), (AD=1119,0360, SD=708,98952 vs CTRL=775,2623 SD=341,67835). However, there was a significant difference between groups concerning t‐Tau protein, (U=198,500; p=0,028), p‐Tau (U=250,00, p=0,001) and p‐Tau/Aβ‐42 ratio (U=238,00; p=0,005). In terms of cognitive variables, all showed significant differences between groups: MMSE (U=46,500, p=0,001), SVF (U=39,000; p<0,001), short term memory (U=27,000, p<0,001), recognition (U=72,500,p=0,014), as well as functionality (U=258,500, p<0,001). There was no difference regarding the age (U= 201,500; p=0,109) and formal education (U=201,500, p=0,109). As for the AD groups with positive and negative biomarkers, there was no significant difference in cognitive variables, age, formal education, and functionality. Conclusion: AD group with negative biomarkers non differ in terms of cognition. Comparing the control and AD groups, there were differences in functionality, cognition, and biomarkers. However, comparing AD groups in terms of biomarkers, there was no difference in functionality performance, short‐term memory, fluency and general cognition. Therefore, the biomarkers do not indicate significant cognitive differences in the group of patients with dementia. [ABSTRACT FROM AUTHOR]

Background: Individuals with mild cognitive impairment (MCI) have increased risk to convert to Alzheimer's dementia (AD). Our aim was to evaluate the role of auditory evoked potential N200 and P300 and serum level of BDNF in predicting conversion from MCI patients to AD, considering APOE and BDNF genetic background. Method: 32 MCI patients were prospectively evaluated. They underwent annual geriatric evaluation and neuropsychological assessment. Cognitive and functional status were established considering both neuropsychology and geriatrics evaluation. AD was diagnosed based on McKhann criteria. Genotyping of APOE alleles and BDNF (Val66Met) was performed by real time PCR. Participants were divided in carriers of APOE ε‐4 allele (APOE4+) and non‐carriers (APOE4‐). At baseline, BDNF concentration was assessed by ELISA methodology and, the participants were also submitted to evoked potential tests (N200 and P300) by means of auditory stimuli based on the auditory oddball paradigm. APOE+ were compared with APOE‐. Anova statistical methods, Bonferroni post‐hoc analysis, Mann Whitney and Student T tests were used, in addition to the evaluation of median, mean and standard deviation. Result: At baseline, participants had a mean age of 74.78 ± 8.35 years, 4.61 ± 3.96 years of formal education. 60.9% were female. The follow‐up mean time was 4.02 ± 1.93 years. During the follow‐up period, 11 MCI participants converted to AD (MCI‐c) and 22 remained stable (MCI‐nc). 34.9% of total sample were APOE+. We did not observe any statistical difference in N200 latency (p = 0.715), P300 latency (p = 0.993) and P300 amplitude (p = 0.574) between MCI‐c and MCI‐nc. However, among APOE+ MCI patients who converted to AD, a significant difference was observed in P300 latency in relation to MCI‐nc (419.63 ± 29.74 versus 349.85 ± 35.82ms, p value: 0.023). We did not observe a relationship between BDNF serum level and conversion to AD (p: 0.061). Nevertheless, in Val/Val BDNF genotype, higher BDNF was associated with conversion to AD (10093.03 ± 3055.49pg / ml versus 5755, 85 ± 1873.20pg / ml, p‐value: 0.017). Conclusion: P300 latency and serum BDNF level in APOE+ and Val/Val BDNF genotype patients are related to conversion of MCI to AD. [ABSTRACT FROM AUTHOR]