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1.
Cir Esp (Engl Ed) ; 2024 Jun 20.
Article En | MEDLINE | ID: mdl-38908514

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

2.
Cir Cir ; 92(3): 399-402, 2024.
Article En | MEDLINE | ID: mdl-38862120

Massive bleeding due to rupture of hypogastric artery pseudoaneurysm is an exceptional complication of colorectal anastomotic leakage. A 41-year-old woman with history of rectal cancer surgery, who debuted with massive rectorrhagia and hypovolemic shock due to rupture of a hypogastric artery pseudoaneurysm as a late complication of a colorectal anastomosis leak. The ruptured hypogastric artery pseudoaneurysm should be taken into account in the differential diagnosis of patients with massive rectorrhagia and history of colorectal anastomosis leak. Endovascular embolization is considered the first-line treatment.


La hemorragia masiva por rotura de un pseudoaneurisma de la arteria hipogástrica es una complicación muy rara de la fuga anastomótica colorrectal. Mujer de 41 años con antecedentes de cirugía por cáncer de recto, que debutó con un cuadro de rectorragias masivo y shock hipovolémico secundario a la rotura de un pseudoaneurisma de la arteria hipogástrica como complicación tardía de una fuga de la anastomosis colorrectal. La rotura de un pseudoaneurisma de la arteria hipogástrica se debe tener presente en el diagnostico diferencial de pacientes con rectorragia masiva y antecedentes de dehiscencia de anastomosis colorrectal. La embolización endovascular es actualmente el tratamiento de elección.


Anastomotic Leak , Aneurysm, False , Shock, Hemorrhagic , Humans , Aneurysm, False/etiology , Female , Adult , Anastomotic Leak/etiology , Shock, Hemorrhagic/etiology , Aneurysm, Ruptured/surgery , Rectum/surgery , Rectal Neoplasms/surgery , Colon/surgery , Colon/blood supply , Anastomosis, Surgical
3.
Curr Oncol Rep ; 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38865004

PURPOSE OF REVIEW: This review aims to summarize the current evidence regarding the prognostic role of frailty in older patients diagnosed with cancer and to explore the evidence regarding its prognostic implications in cancer survivors. RECENT FINDINGS: Frailty has been consistently associated with mortality/overall survival, postoperative complications, short- and long-term postoperative mortality, length of stay, among other adverse health-related outcomes in several oncological contexts. The possible association between frailty and treatment toxicity has been less explored, however most studies suggest frailty is a predictor of treatment induced toxicity. In addition, in cancer survivors, frailty is a risk factor for cardiovascular disease, incident type 2 diabetes mellitus, mortality, altered cognitive performance and increased symptom severity. Due to its usefulness in establishing prognosis and informing treatment decision making, it is expected that frailty screening and assessment will continue to gain popularity as part of the pretreatment evaluation of older patients with cancer.

4.
AIDS Care ; : 1-11, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38838046

The number of older people living with HIV (OPLHIV) is increasing worldwide. However, little is known about the factors that better predict their health-related quality of life (HRQoL). We administered the validated WHOQoL-HIV BREF questionnaire to 247 Spanish OPLHIV (192 men and 55 women). In addition to the six domains of the questionnaire, we constructed a seventh domain as theaverage of punctuations of all domains. Multivariable Poisson regression models with robust estimates by sex were constructed for the seven domains (14 in total). The best-subset selection method together with Mallow's Cp metric was used to select the model factors. The percentage of variability explained by Poisson models ranged from15-38% for men and 29-70% for women. The analysis showed that women were most affected by ageing (four domains), mobility impairments (five domains), and mental disorders (five domains). The factors with the greatest negative influence on men were heterosexuality (six domains), mental disorders (six domains), being single (five domains), and poverty risk (three domains). Physical activity was found to improve HRQoL in both men (six domains) and women (four domains). Future OPLHIV programmes would benefit from considering sex specific HRQoL factors. This could also improve the cost-effectiveness of interventions.

5.
BMC Infect Dis ; 24(1): 634, 2024 Jun 25.
Article En | MEDLINE | ID: mdl-38918705

BACKGROUND: CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels. METHODS: This is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes. RESULTS: The main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2). CONCLUSIONS: We conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.


Anti-Bacterial Agents , Bacteremia , Methicillin-Resistant Staphylococcus aureus , Renal Dialysis , Renal Insufficiency, Chronic , Staphylococcal Infections , Vancomycin , Humans , Vancomycin/therapeutic use , Retrospective Studies , Bacteremia/drug therapy , Bacteremia/microbiology , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Male , Renal Dialysis/adverse effects , Female , Renal Insufficiency, Chronic/complications , Aged , Methicillin-Resistant Staphylococcus aureus/drug effects , Middle Aged , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Aged, 80 and over , Microbial Sensitivity Tests
6.
Int J Mol Sci ; 25(11)2024 Jun 05.
Article En | MEDLINE | ID: mdl-38892419

The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota-gut-brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.


Brain-Gut Axis , Gastrointestinal Microbiome , Brain-Gut Axis/physiology , Enterococcus faecalis/physiology , Escherichia coli , Glutamic Acid/metabolism , gamma-Aminobutyric Acid/metabolism , Membrane Potentials , Humans
7.
PLoS One ; 19(5): e0301335, 2024.
Article En | MEDLINE | ID: mdl-38713682

BACKGROUND: Current antiretroviral therapies have increased the life expectancy of people living with HIV (PLHIV). There is, however, limited evidence regarding the health-related quality of life (HRQoL) and living conditions of older people living with HIV (OPLHIV) in Spain. METHODS: We implemented a self-administered online questionnaire to identify sex differences in HRQoL and poverty risk among Spanish OPLHIV (PLHIV ≥50 years). Participants were contacted through non-governmental organisations. We used the standardised WHOQoL-HIV BREF questionnaire and the Europe 2020 guidelines to estimate HRQoL and poverty risk respectively. The statistical analysis included multivariable generalised linear models with potential confounding variables and robust estimates. RESULTS: The study included 247 OPLHIV (192 men and 55 women). On the WHOQoL-HIV BREF questionnaire, men scored higher on 84% of items and in all six domains. Women had significantly lower HRQoL in five domains: physical health (ß: -1.5; 95% CI: -2.5, -0.5; p: 0.002), psychological health (ß: -1.0; 95% CI: -1.9, -0.1; p: 0.036), level of independence (ß: -1.1; 95% CI: -1.9, -0.2; p: 0.019), environmental health (ß: -1.1; 95% CI: -1.8, -0.3; p: 0.008), and spirituality/personal beliefs (ß: -1.4; 95% CI: -2.5, -0.3; p: 0.012). No statistical differences were found in the domain of social relations. Poverty risk was considerable for both men (30%) and women (53%), but women were significantly more likely to experience it (OR: 2.9; 95% CI: 1.3, 6.5; p: 0.009). CONCLUSION: The aging of PLHIV is a public health concern. Our findings indicate that HRQoL and poverty risk among Spanish OPLHIV differ significantly by sex. Spain should, therefore, implement specific policies and interventions to address OPLHIV needs. The strategies must place a high priority on the reduction of sex inequalities in HRQoL and the enhancement of the structural conditions in which OPLHIV live.


HIV Infections , Poverty , Quality of Life , Humans , Male , Female , Spain/epidemiology , HIV Infections/psychology , HIV Infections/epidemiology , HIV Infections/drug therapy , Cross-Sectional Studies , Middle Aged , Aged , Surveys and Questionnaires , Sex Factors
8.
Sensors (Basel) ; 24(10)2024 May 10.
Article En | MEDLINE | ID: mdl-38793882

In this work, we experimentally analyzed and demonstrated the performance of an in-line Mach-Zehnder interferometer in the visible region, with an LED light source. The different waist diameter taper and asymmetric core-offset interferometers proposed used a single-mode fiber (SMF). The visibility achieved was V = 0.14 with an FSR of 23 nm for the taper MZI structure and visibilities of V = 0.3, V = 0.27, and V = 0.34 with FSRs of 23 nm, 17 nm, and 8 nm and separation lengths L of 2.5 cm, 4.0 cm, and 5.0 cm between the core-offset structure, respectively. The experimental investigation of the response to the temperature sensor yielded values from 50 °C to 300 °C; the sensitivity obtained was 3.53 a.u./°C, with R2 of 0.99769 and 1% every 1 °C in the transmission. For a range of 50 °C to 150 °C, 20.3 pm/°C with a R2 of 0.96604 was obtained.

9.
Nutrients ; 16(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38794704

Bariatric surgery therapy (BST) is an effective treatment for obesity; however, little is known about its impacts on health-related quality of life (HRQoL) and related factors. This study aimed to evaluate changes in HRQoL and its relationship with weight loss, depression status, physical activity (PA), and nutritional habits after BST. Data were obtained before and 18 months postprocedure from 56 obese patients who underwent BST. We administered four questionnaires: Short Form-36 health survey for HRQoL, 14-item MedDiet adherence questionnaire, Rapid Assessment of PA (RAPA) questionnaire, and Beck's Depression Inventory-II. Multivariable linear regression analysis was used to identify factors associated with improvement in HRQoL. After the surgery, MedDiet adherence and HRQoL improved significantly, especially in the physical component. No changes in PA were found. Patients without previous depression have better mental quality of life, and patients who lost more than 25% of %TBWL have better results in physical and mental quality of life. In the multivariable analysis, we found that %TBWL and initial PCS (inversely) were related to the improvement in PCS and initial MCS (inversely) with the MCS change. In conclusion, BST is an effective intervention for obesity, resulting in significant weight loss and improvements in HRQoL and nutritional habits.


Bariatric Surgery , Depression , Exercise , Obesity , Quality of Life , Weight Loss , Humans , Bariatric Surgery/psychology , Female , Male , Adult , Middle Aged , Obesity/surgery , Obesity/psychology , Depression/psychology , Exercise/psychology , Surveys and Questionnaires , Feeding Behavior/psychology , Treatment Outcome
10.
Animals (Basel) ; 14(10)2024 May 18.
Article En | MEDLINE | ID: mdl-38791719

Biological invasions are of special conservation concern in the Iberian Peninsula and other regions with high levels of endemism. Environmental variability, such as the seasonal fluctuations of Mediterranean streams, is a key factor that affects the spread of aquatic species in novel habitats. Fish parasites have a great potential to reflect such changes in the habitat features of freshwater ecosystems. The aim of this study consisted of seasonally analysing the health status and parasitological traits of non-native fish in Iberian waters. In particular, a strongly invasive population of Languedoc minnow Phoxinus septimaniae (leuciscid species native to south-east France) was assessed in Tordera Stream (north-eastern Iberian Peninsula, Mediterranean conditions). Fish were sampled in April, July, and October 2023 by electrofishing. Health status (external/internal organs) was significantly better in autumn (HAI = 28.8) than spring (HAI = 35.6). Life-cycle complexity was higher in spring (LCI = 1.98), whereas parasite abundance and Shannon diversity were significantly lower in autumn (TA = 19.6 and H' = 2.15, respectively). In October (more 'benign' environmental conditions in Iberian streams), minnows could display elevated foraging activity, with fish increasing their health condition and level of parasite resistance/tolerance. Overall results showed a particular seasonal profile of health and parasite infra-communities that allow this minnow species to thrive under highly fluctuating habitat conditions. This information could help environmental managers to control non-native fish in Mediterranean streams.

11.
Blood Adv ; 2024 May 22.
Article En | MEDLINE | ID: mdl-38776397

BCMA-targeting CAR-T cells used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (RR) disease, and CAR-T cell expansion post-infusion has been shown to inform depth and duration of response, but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 relapsed MM patients treated with the BCMA-targeting agents cilta-cel and ide-cel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and duration of response (DoR). Patients with ALCmax >1.0 x103/uL had a superior PFS (30.5 versus 6 months, p <0.001) compared to those ≤1.0x103/uL, while patients with ALCmax ≤0.5 x103/uL represent a high-risk group with early disease progression and short PFS (HR 3.4, 95 CI: 2 -5.8, P <0.001). In multivariate analysis, ALCmax >1.0 x103/uL and non-paraskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for ISS staging, age, CAR-T product, high-risk cytogenetics and number of previous lines. Moreover, our flow cytometry data suggests that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in RRMM patients.

14.
Cuad Bioet ; 35(113): 27-40, 2024.
Article Es | MEDLINE | ID: mdl-38734921

The consumption of pornography over the Internet by minors has been increasing exponentially in recent years. The use of digital technologies and the ease of access to these contents are causes that explain this event. Simultaneously, there is concern about the increase in sexual violence, associated with discriminatory behavior, despite the efforts of laws and programs that promote sexual reproductive health (SRH) and the principle of equality. From a bioethical point of view, it is urgent to address this issue, which affects the physical and psychological health of minors and their affective-sexual education. The study addresses whether it is possible to relate the consumption of online pornography by minors and sexual violence. To do this, legal sources, reports from associations, audiovisual councils and scientific studies are consulted. In all of them, the relationship between the consumption of online pornography by adolescents and risky behavior in emotional-sexual matters and gender inequality is evident. In the legal and fiscal sphere, it is alerted to the damage that is occurring and points out the need to propose lines of action that reverse this situation. We propose measures to technically regulate access to content. These measures are based on the precautionary principle, a tool that has been applied in fields such as health and the environment. More studies and political actions are needed to make the Internet a safe place for minors.


Erotica , Internet , Erotica/legislation & jurisprudence , Erotica/psychology , Humans , Adolescent , Minors/legislation & jurisprudence , Minors/psychology , Female , Male , Child , Sex Offenses/legislation & jurisprudence , Sex Offenses/psychology
15.
J Inflamm (Lond) ; 21(1): 15, 2024 May 02.
Article En | MEDLINE | ID: mdl-38698414

INTRODUCTION: PM exposure can induce inflammatory and oxidative responses; however, differences in these adverse effects have been reported depending on the chemical composition and size. Moreover, inflammatory mechanisms such as NLRP3 activation by PM10 have yet to be explored. OBJECTIVE: To assess the impact of PM10 on cell cytotoxicity and the inflammatory response through in vitro and in vivo models. METHODOLOGY: Peripheral blood mononuclear cells (PBMCs) from healthy donors were exposed to PM10. Cytotoxicity was determined using the LDH assay; the expression of inflammasome components and the production of pro-inflammatory cytokines were quantified through qPCR and ELISA, respectively; and the formation of ASC complexes was examined using confocal microscopy. For in vivo analysis, male C57BL6 mice were intranasally challenged with PM10 and bronchoalveolar lavage fluid was collected to determine cell counts and quantification of pro-inflammatory cytokines by ELISA. RNA was extracted from lung tissue, and the gene expression of inflammatory mediators was quantified. RESULTS: PM10 exposure induced significant cytotoxicity at concentrations over 100 µg/mL. Moreover, PM10 enhances the gene expression and release of pro-inflammatory cytokines in PBMCs, particularly IL-1ß; and induces the formation of ASC complexes in a dose-dependent manner. In vivo, PM10 exposure led to cell recruitment to the lungs, which was characterized by a significant increase in polymorphonuclear cells compared to control animals. Furthermore, PM10 induces the expression of several inflammatory response-related genes, such as NLRP3, IL-1ß and IL-18, within lung tissue. CONCLUSION: Briefly, PM10 exposure reduced the viability of primary cells and triggered an inflammatory response, involving NLRP3 inflammasome activation and the subsequent production of IL-1ß. Moreover, PM10 induces the recruitment of cells to the lung and the expression of multiple cytokines; this phenomenon could contribute to epithelial damage and, thus to the development and exacerbation of respiratory diseases such as viral infections.

16.
J Dairy Res ; 91(1): 19-24, 2024 Feb.
Article En | MEDLINE | ID: mdl-38757385

The objective of this study was to determine the effect of dietary calcium soaps from garlic (Allium sativum) and willow (Salix babylonica) extracts on nematode loads, nutrient intake and digestibility, nitrogen balance and rumen fermentation kinetics in dairy goats. Nine adult non-lactating Saanen goats were grouped into a complete randomized block design with 3 treatments (n = 3) over a period of 28 d. Animals were fed a diet based on alfalfa hay and a concentrate that was supplemented (65 g/kg DM) with calcium soaps of safflower (control), garlic or willow. Intake of dry matter (DM), organic matter (OM) and neutral detergent fiber (NDF) were not affected by dietary calcium soaps. However, the highest digestibility of DM and OM were observed in willow supplemented goats. In vitro gas kinetics and fermentation profile were not affected by diets. Results from fecal egg count indicated a reduction in total count, Haemonchus spp. and Trychostrongylus spp. for both garlic and willow compared to control. Our results suggest that calcium soaps of garlic or willow extracts can be used to reduce gastrointestinal parasites in goats without compromising productive traits or rumen function.


Animal Feed , Diet , Digestion , Fermentation , Garlic , Goats , Nitrogen , Plant Extracts , Rumen , Salix , Animals , Goats/physiology , Garlic/chemistry , Salix/chemistry , Rumen/parasitology , Rumen/metabolism , Digestion/drug effects , Nitrogen/metabolism , Female , Plant Extracts/pharmacology , Animal Feed/analysis , Diet/veterinary , Goat Diseases/parasitology , Goat Diseases/prevention & control , Dietary Supplements , Nematoda/drug effects , Nutrients , Feces/parasitology , Feces/chemistry , Parasite Egg Count/veterinary , Animal Nutritional Physiological Phenomena , Calcium
17.
Life (Basel) ; 14(5)2024 May 20.
Article En | MEDLINE | ID: mdl-38792669

Patients with fibromyalgia syndrome tend to report deficits in cognitive functions; however, there is no clear consensus on which cognitive domains are impaired. The aim of this study was to compare the differences in cognitive performance between a group of patients with fibromyalgia syndrome and a group of pain-free subjects controlling for the covariables anxiety, depression, and sleep quality. In total, 130 patients with fibromyalgia syndrome and 111 pain-free subjects with an average age of 54.96 years completed the evaluation protocol consisting of sociodemographic data, psychological data, and neurocognitive tests. All data were collected from May 2022 to May 2023. Multivariate analyses of covariance (MANCOVAs) were conducted to assess intergroup differences in all neurocognitive tests. MANCOVA analyses showed that the group of patients with fibromyalgia showed a worse cognitive performance than the group of pain-free subjects after controlling for anxiety, depression, and sleep quality. This study found that fibromyalgia patients exhibited worse cognitive performance and executive function than pain-free subjects. Thus, cognitive performance seems to not be related with anxiety, depression, or sleep quality in our sample of women with FMS.

18.
Front Microbiol ; 15: 1346639, 2024.
Article En | MEDLINE | ID: mdl-38812688

In cats and humans, several physiological and environmental factors have been shown to alter the gut microbiota of healthy individuals. Cats share several diseases with humans such as inflammatory bowel diseases and low-grade intestinal T-cell lymphoma. The physiopathology of these chronic enteropathies is poorly understood but may involve disequilibrium of the gut microbiota composition and disruption of normal microbiome activity profiles. These disorders are increasingly diagnosed in the feline species due to improved medicalization and easier access to endoscopy in veterinary practice. This review addresses the current data on the gut microbiota of cats in health and in chronic enteropathies. Such functional analysis will help the advancement of innovative diagnostic tools and targeted therapeutic strategies.

20.
Ageing Res Rev ; 96: 102290, 2024 Apr.
Article En | MEDLINE | ID: mdl-38580173

Biomarkers that predict the clinical onset of Alzheimer's disease (AD) enable the identification of individuals in the early, preclinical stages of the disease. Detecting AD at this point may allow for more effective therapeutic interventions and optimized enrollment for clinical trials of novel drugs. The current biological diagnosis of AD is based on the AT(N) classification system with the measurement of brain deposition of amyloid-ß (Aß) ("A"), tau pathology ("T"), and neurodegeneration ("N"). Diagnostic cut-offs for Aß1-42, the Aß1-42/Aß1-40 ratio, tau and hyperphosphorylated-tau concentrations in cerebrospinal fluid have been defined and may support AD clinical diagnosis. Blood-based biomarkers of the AT(N) categories have been described in the AD continuum. Cross-sectional and longitudinal studies have shown that the combination of blood biomarkers tracking neuroaxonal injury (neurofilament light chain) and neuroinflammatory pathways (glial fibrillary acidic protein) enhance sensitivity and specificity of AD clinical diagnosis and improve the prediction of AD onset. However, no international accepted cut-offs have been identified for these blood biomarkers. A kit for blood Aß1-42/Aß1-40 is commercially available in the U.S.; however, it does not provide a diagnosis, but simply estimates the risk of developing AD. Although blood-based AD biomarkers have a great potential in the diagnostic work-up of AD, they are not ready for the routine clinical use.


Alzheimer Disease , Humans , Alzheimer Disease/metabolism , tau Proteins , Cross-Sectional Studies , Amyloid beta-Peptides , Biomarkers/cerebrospinal fluid
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