Characterization of a cohort of patients with hypercalcemia in a tertiary pediatric hospital. / Caracterización de una cohorte de pacientes con hipercalcemia en un centro pediátrico de tercer nivel.

Introduction. Hypercalcemia is infrequent in pediatrics, of diverse etiology, and with multiorgan morbidity. Objective. Describe the etiology, biochemistry, clinical, and treatment in pediatric patients with hypercalcemia. Population and methods. Retrospective and descriptive study of a cohort of patients with hypercalcemia between 2008 and 2022. They were classified into three groups (G): hypercalcemia of iatrogenic cause (G1), parathyroid hormone (PTH) independent (G2), or PTH-dependent (G3). Results. One hundred forty-seven patients were included; 57% were male, with a median age of 3.7 years, median calcemia of 11.8 mg/dl, and mean phosphatemia of 4.9 mg/dl. Symptoms were present in 29% of patients, and 28.6% required additional treatments to those of the first line. In G1, 76 patients (51.7%) were included; in G2, 58 (39.4%), and in G3, 13 (8.8%). Median calcemia was lower in G1 vs. G2 and G3 (11.6 mg/dl, 12.6 mg/dl, and 12.3 mg/dl), and mean phosphatemia was lower in G3 vs. G1 and G2 (3.7 mg/dl, 5.3 mg/dl, and 4.9 mg/dl). Most of the patients with hypercalcemia were asymptomatic and did not require additional treatments. The percentage of symptomatic patients and the percentage requiring additional treatment were lower in G1 than in the other two groups. Conclusions. Iatrogenesis was the most frequent cause, presenting lower calcemia, while PTH-dependent causes presented the lowest phosphatemia. PTH-independent causes represented a diagnostic and therapeutic challenge due to lacking a characteristic biochemical profile.

Introducción. La hipercalcemia es infrecuente en pediatría, de etiología diversa y con morbilidad multiorgánica. Objetivo. Describir etiología, bioquímica, clínica y tratamiento en pacientes pediátricos con hipercalcemia. Población y métodos. Estudio retrospectivo y descriptivo de una cohorte de pacientes con hipercalcemia entre 2008 y 2022. Se clasificaron en tres grupos (G): hipercalcemia de causa iatrogénica (G1), paratohormona (PTH) independiente (G2) o PTH dependiente (G3). Resultados. Se incluyeron 147 pacientes; el 57 % eran varones, edad mediana de 3,7 años, calcemia mediana 11,8 mg/dl y fosfatemia media 4,9 mg/dl. El 29,9 % de los pacientes fueron sintomáticos y el 28,6 % requirió tratamientos adicionales a los de la primera línea. En G1 se incluyeron 76 pacientes (51,7 %); en G2, 58 (39,4 %), y en G3, 13 (8,8 %). La calcemia mediana fue menor en G1 vs. G2 y G3 (11,6 mg/dl, 12,6 mg/dl y 12,3 mg/dl). La fosfatemia media fue menor en G3 vs. G1 y G2 (3,7 mg/dl, 5,3 mg/dl y 4,9 mg/dl). La mayoría de los pacientes con hipercalcemia fueron asintomáticos sin requerimientos de tratamientos adicionales. El porcentaje de pacientes sintomáticos y el de requerimiento de tratamientos adicionales fue menor en G1 que en los otros dos grupos. Conclusiones. La iatrogenia fue la causa más frecuente, y se presentó con calcemias más bajas; mientras que las causas PTH dependientes presentaron las fosfatemias más bajas. Las causas PTH independientes representaron un desafío diagnóstico y terapéutico por la falta de un perfil bioquímico característico.

ABCD syndrome, an uncommon cause of hypercalcemia in pediatrics. / Síndrome ABCD, una causa infrecuente de hipercalcemia en pediatría.

ABCD syndrome (ABnormal Calcium, Calcinosis, and Creatinine in Down syndrome) is characterized by an association of hypercalcemia, hypercalciuria, nephrocalcinosis, and impaired kidney function in patients with Down syndrome. Only 7 cases have been published worldwide, although it is believed to be underdiagnosed. This report describes 2 new patients with ABCD syndrome and compares them with the cases reported to date. Although it is a rare cause of pediatric hypercalcemia, it should be considered in children with Down syndrome once other more common etiologies have been ruled out. Once this diagnosis is confirmed, the recommended treatment is to reduce dietary calcium intake and work with an interdisciplinary team to maintain an adequate calorie and protein intake.

El síndrome ABCD (por sus siglas en inglés, ABnormal Calcium, Calcinosis and Creatinine in Down syndrome) se caracteriza por la asociación de hipercalcemia, hipercalciuria, nefrocalcinosis y alteración de la función renal en pacientes con síndrome de Down. Existen solo 7 casos previamente publicados en el mundo, aunque se cree que está subdiagnosticado. En este reporte, presentamos 2 nuevos pacientes con este síndrome y realizamos una comparación con los casos informados hasta el momento. Si bien es una causa rara de hipercalcemia pediátrica, debe considerarse en niños con síndrome de Down una vez descartadas otras etiologías más frecuentes. Al confirmarse este diagnóstico, el tratamiento recomendado es la reducción de calcio en la dieta, trabajando de manera interdisciplinaria para mantener un aporte calórico proteico adecuado.

Surgical treatment of secondary hyperparathyroidism in children with chronic kidney disease. Experience in 19 patients.

OBJECTIVES: Secondary hyperparathyroidism (sHPT) is an important contributor to bone disease and cardiovascular calcifications in children with chronic kidney disease (CKD). When conservative measures are ineffective, parathyroidectomy is indicated. The aim of our study was to evaluate the efficacy and safety of subtotal parathyroidectomy (sPTX) in pediatric and adolescent patients, and to provide a rationale for considering this aggressive treatment in CKD patients with uncontrolled sHPT. METHODS: We retrospectively analyzed the medical records of 19 pediatric CKD patients on dialysis with refractory sHPT who underwent sPTX at our institution between 2010 and 2020. All patients had clinical, radiological, and biochemical signs of renal osteodystrophy. RESULTS: One year after sPTX, parathyroid hormone (PTH) levels (median and interquartile range (IQR)) dropped from 2073 (1339-2484) to 164 (93-252) pg/mL (p=0.0001), alkaline phosphatase (ALP) levels from 1166 (764-2373) to 410 (126-421) IU/L (p=0.002), and the mean (±SDS) calcium-phosphate (Ca*P) product from 51±11 to 41±13 mg2/dL2 (p=0.07). Postoperatively, all patients presented with severe hungry bone syndrome (HBS) and required intravenous and oral calcium and calcitriol supplementation. None of them had other postoperative complication. Histological findings had a good correlation with preoperative parathyroid ultrasound imaging (n: 15) in 100 % and with technetium-99m (99mTc) sestamibi scintigraphy (n: 15) in 86.6 %. Clinical and radiological signs of bone disease improved in all patients. CONCLUSIONS: Pediatric sPTX is effective and safe to control sHPT and calcium-phosphate metabolism in children with CKD on dialysis and may mitigate irreversible bone deformities and progression of cardiovascular disease.

AI4FoodDB: a database for personalized e-Health nutrition and lifestyle through wearable devices and artificial intelligence.

The increasing prevalence of diet-related diseases calls for an improvement in nutritional advice. Personalized nutrition aims to solve this problem by adapting dietary and lifestyle guidelines to the unique circumstances of each individual. With the latest advances in technology and data science, researchers can now automatically collect and analyze large amounts of data from a variety of sources, including wearable and smart devices. By combining these diverse data, more comprehensive insights of the human body and its diseases can be achieved. However, there are still major challenges to overcome, including the need for more robust data and standardization of methodologies for better subject monitoring and assessment. Here, we present the AI4Food database (AI4FoodDB), which gathers data from a nutritional weight loss intervention monitoring 100 overweight and obese participants during 1 month. Data acquisition involved manual traditional approaches, novel digital methods and the collection of biological samples, obtaining: (i) biological samples at the beginning and the end of the intervention, (ii) anthropometric measurements every 2 weeks, (iii) lifestyle and nutritional questionnaires at two different time points and (iv) continuous digital measurements for 2 weeks. To the best of our knowledge, AI4FoodDB is the first public database that centralizes food images, wearable sensors, validated questionnaires and biological samples from the same intervention. AI4FoodDB thus has immense potential for fostering the advancement of automatic and novel artificial intelligence techniques in the field of personalized care. Moreover, the collected information will yield valuable insights into the relationships between different variables and health outcomes, allowing researchers to generate and test new hypotheses, identify novel biomarkers and digital endpoints, and explore how different lifestyle, biological and digital factors impact health. The aim of this article is to describe the datasets included in AI4FoodDB and to outline the potential that they hold for precision health research. Database URL https://github.com/AI4Food/AI4FoodDB.

Prevalent Technique and Results of Hemorrhoidal Embolization.

Hemorrhoids are blood cushions located in the anus and lower rectum, acknowledged as a common cause of bleeding, which can reduce quality of life. The development of minimally invasive techniques such as endovascular embolization of superior rectal artery, "Emborrhoid technique", is an effective treatment, with no pain or ischemic complications, and allows quick patient recovery. Our purpose is to describe the general technique and discuss the results of the current literature.

Automatized FACEmemory® scoring is related to Alzheimer's disease phenotype and biomarkers in early-onset mild cognitive impairment: the BIOFACE cohort.

BACKGROUND: FACEmemory® is the first computerized, self-administered verbal episodic memory test with voice recognition. It can be conducted under minimal supervision and contains an automatic scoring system to avoid administrator errors. Moreover, it is suitable for discriminating between cognitively healthy and amnestic mild cognitive impairment (MCI) individuals, and it is associated with Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers. This study aimed to determine whether FACEmemory scoring is related to performance on classical memory tests and to AD biomarkers of brain magnetic resonance imaging (MRI) and CSF in patients with early-onset MCI (EOMCI). METHODS: Ninety-four patients with EOMCI from the BIOFACE study completed FACEmemory, classical memory tests (the Spanish version of the Word Free and Cued Selective Reminding Test -FCSRT-, the Word List from the Wechsler Memory Scale, third edition, and the Spanish version of the Rey-Osterrieth Complex Figure Test), and a brain MRI. Eighty-two individuals also underwent a lumbar puncture. RESULTS: FACEmemory scoring was moderately correlated with FCSRT scoring. With regard to neuroimaging MRI results, worse execution on FACEmemory was associated with lower cortical volume in the right prefrontal and inferior parietal areas, along with the left temporal and associative occipital areas. Moreover, the total FACEmemory score correlated with CSF AD biomarkers (Aß1-42/Aß1-40 ratio, p181-tau, and Aß1-42/p181-tau ratio). When performance on FACEmemory was compared among the ATN classification groups, significant differences between the AD group and normal and SNAP groups were found. CONCLUSIONS: FACEmemory is a promising tool for detecting memory deficits sensitive to early-onset AD, but it also allows the detection of memory-impaired cases due to other etiologies. Our findings suggest that FACEmemory scoring can detect the AD endophenotype and that it is also associated with AD-related changes in MRI and CSF in patients with EOMCI. The computerized FACEmemory tool might be an opportunity to facilitate early detection of MCI in younger people than 65, who have a growing interest in new technologies.

Pediatric adrenocortical tumors cohort characteristics and long-term follow-up at a single Argentinian tertiary center.

Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies. OBJECTIVES: To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center. METHODS: A retrospective review of medical records of children with PACT (diagnosed before <18 years of age) followed between 1987-2018 at Hospital de Pediatría Garrahan, Buenos Aires, Argentina. RESULTS: Mean age at diagnosis was 4.6 years (range, 0.3-17.3 years) and median follow-up was 4.17 years (range, 0-12 years). Female to male ratio was 2.5:1. Signs and symptoms that prompted medical intervention were hormonal overproduction (57%), abdominal complaints (36%), and hypertensive encephalopathy (7%). In patients with clinically virilizing tumors (n=16) mean height standard deviation score (SDS) and bone age advance were significantly higher while body mass index (BMI) SDS was significantly lower than in those with clinical Cushing's (n=10) (p<0.05). Serum dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in stage IV than in stage I (p=0.03). Total adrenalectomy was performed in 26 patients. Eight patients (stage III-IV) received adjuvant chemotherapy. Five-year overall and disease-free survival were 100% for ST I-II, and 51% (95% CI 21-82) and 33% (95% CI 1.2-65) for ST III-IV, respectively (p=0.002). No statistical difference was found when comparing 2-year parameters with and without adjuvant chemotherapy. CONCLUSIONS: Height SDS and BMI SDS seem to mirror hormonal secretion in pediatric adrenocortical tumors. Higher DHEAS levels were found in patients with more advanced disease. Further large-scale studies are needed to validate a possible role for DHEAS as a biochemical marker of tumor stage and to draw robust conclusions on the use of adjuvant chemotherapy.

Clinical and epidemiological characteristics of mothers with COVID-19 and their neonates: vertical transmission. / Características clínicas y epidemiológicas de madres con COVID-19 y sus neonatos: transmisión vertical.

INTRODUCTION: COVID-19 disease can affect women at any stage of pregnancy, and newborns could become infected with SARS-CoV-2 through vertical or horizontal transmission. OBJECTIVE: To determine clinical and epidemiological characteristics of mothers with COVID-19, associated neonatal outcomes, and to evaluate SARS-CoV-2 vertical transmission. METHODS: We conducted an observational, descriptive, cross-sectional study. We included all mothers with positive serology for SARS-CoV-2 and their newborns at the Hospital Regional Docente de Trujillo from April 18 to September 30, 2020. Variables were collected from the medical records, and descriptive statistics were used for the analysis. RESULTS: A total of 647 mothers and 656 neonates were enrolled. Of all live births, 85.3% and 14.7% were term and preterm neonates, respectively. We found 1.7% (11/656) of newborns with positive RT-PCR for SARS-CoV-2; and that 27.3% (3/11) of these neonates required hospitalization. Neonatal mortality was 4/656 (0.6%), and no case was attributed to COVID-19. Of all mothers affected with COVID-19, 95.7% were asymptomatic, and 4.3% presented clinical symptoms attributed to COVID-19, most of which were mild. The most frequent obstetric complications were preeclampsia-eclampsia, prelabour rupture of membranes, and acute fetal distress. All the mothers were discharged. CONCLUSION: We found 1.7% of newborns with positive RT-PCR test for SARS-CoV-2; and that 20.1% of these neonates were hospitalized. The most frequent morbidity was neonatal sepsis and prematurity. The infection was mild among newborns, showing a 0.6% overall mortality, with no cases attributed to COVID-19. We found that only 5% of mothers presented symptoms, most of which were mild to moderate symptoms. There was no record of maternal mortality in this study group. It is not possible to conclude whether vertical transmission or intrapartum-acquired infection is responsible for neonatal COVID-19 infections.

INTRODUCCIÓN: La enfermedad de COVID-19 puede afectar a gestantes en cualquier trimestre del embarazo. Por su parte, los neonatos podrían infectarse con SARS-CoV-2 por transmisión vertical u horizontal. OBJETIVO: Determinar las características clínicas y epidemiológicas de madres con COVID-19, de sus neonatos y la transmisión vertical del SARS-CoV-2. MÉTODOS: Estudio observacional, descriptivo, transversal. Se incluyeron todas las madres con serología positiva para SARS-CoV-2 y sus neonatos nacidos en el Hospital Regional Docente de Trujillo desde el 18 de abril hasta el 30 de septiembre de 2020. La información para las variables se recogió de las historias clínicas. Para el análisis se usó estadística descriptiva. RESULTADOS: Participaron 647 madres y 656 neonatos. El 85,3% de los neonatos nació de término y el 14,7% fue prematuro. El 1,7% (11/656) tuvieron PCR-RT positivos para SARS-CoV-2, y de ellos el 27,3% (3/11) requirió hospitalizados. La mortalidad fue de 4/656 (0,6%), no atribuida a COVID-19. De las madres afectadas con COVID-19, 95,7% fue asintomática, el 4,3% presentó sintomatología clínica atribuida a COVID-19, siendo en su mayoría casos leves. Las complicaciones obstétricas más frecuentes fueron preeclampsia, eclampsia, rotura prematura de las membranas y sufrimiento fetal agudo. Todas las madres fueron dadas de alta. CONCLUSIÓN: De los neonatos estudiados, el 1,7% presentó prueba PCR-RT para SARS-CoV-2 positiva. El 20,1% fue hospitalizado. La morbilidad más frecuente fue sepsis neonatal y prematuridad. La mortalidad fue de 0,6%, ningún caso atribuido a COVID-19. El cuadro clínico de esta patología fue leve en los neonatos. El 95% de las madres con COVID-19 fueron asintomáticas. De las gestantes que presentaron cuadro clínico, tuvieron sintomatología leve a moderada. No se tuvo registro de mortalidad materna en el grupo de estudio. No se puede concluir si se trata de casos de transmisión vertical del SARS-CoV-2 o estamos frente a casos de posible infección neonatal adquirida intraparto.

BIOFACE: A Prospective Study of Risk Factors, Cognition, and Biomarkers in a Cohort of Individuals with Early-Onset Mild Cognitive Impairment. Study Rationale and Research Protocols.

BACKGROUND: Mild cognitive impairment (MCI) due to Alzheimer's disease (AD) diagnosis is based on cerebrospinal fluid (CSF) or neuroimaging biomarkers. Currently, non-invasive and inexpensive blood-based biomarkers are being investigated, such as neuronal-derived plasma exosomes (NPEs). Neuroinflammation and early vascular changes have been described in AD pathogenesis and can be traced in plasma and NPEs. However, they have not been studied in early onset MCI (EOMCI). OBJECTIVE: To describe the rationale, design, and baseline characteristics of the participants from the BIOFACE cohort, a two-year observational study on EOMCI conducted at Fundació ACE. The study goal is to characterize the different phenotypes from a clinical, neuropsychological, and biomarker point of view and to investigate the CSF and plasma proteomics as well as the role of NPEs as early biomarkers of AD. METHODS: Participants underwent extended neurological and neuropsychological batteries, multimodal biomarkers including brain MRI, blood, saliva, CSF, anthropometric, and neuro-ophthalmological examinations. RESULTS: Ninety-seven patients with EOMCI were recruited. 59.8%were women. Mean age at symptom onset was 57 years; mean MMSE was 28. First degree and presenile family history of dementia was present in 60.8%and 15.5%, respectively. Depressive and anxiety disorders along with vascular risk factors were the most frequent comorbidities. 29%of participants were APOE ɛ4 carriers, and 67%showed a CSF normal ATN profile. CONCLUSION: BIOFACE is a two-year study of clinical, cognition, and biomarkers that will shed light on the physiopathology and the potential utility of plasma and NPEs as non-invasive early diagnostic and prognostic biomarkers in people younger than 65 years.

Significant Decrease in Annual Cancer Diagnoses in Spain during the COVID-19 Pandemic: A Real-Data Study.

The COVID-19 pandemic has caused a profound change in health organizations at both the primary and hospital care levels. This cross-sectional study aims to investigate the impact of the COVID-19 pandemic in the annual rate of new cancer diagnosis in two university-affiliated hospitals. This study includes all the patients with a pathological diagnosis of cancer attended in two hospitals in Málaga (Spain) during the first year of pandemic. This study population was compared with the patients diagnosed during the previous year 2019. To analyze whether the possible differences in the annual rate of diagnoses were due to the pandemic or to other causes, the patients diagnosed during 2018 and 2017 were also compared. There were 2340 new cancer diagnosis compared to 2825 patients in 2019 which represented a decrease of -17.2% (p = 0.0001). Differences in the number of cancer patients diagnosed between 2018 and 2019 (2840 new cases; 0.5% increase) or 2017 and 2019 (2909 new cases; 3% increase) were not statistically significant. The highest number of patients lost from diagnosis in 2020 was in breast cancer (-26.1%), colorectal neoplasms (-16.9%), and head and neck tumors (-19.8%). The study of incidence rates throughout the first year of the COVID-19 pandemic shows that the diagnosis of new cancer patients has been significantly impaired. Health systems must take the necessary measures to restore pre-pandemic diagnostic procedures and to recover lost patients who have not been diagnosed.

Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis.

Neuropsychiatric symptoms (NPS) have been recently addressed as risk factors of conversion to Alzheimer's disease (AD) and other dementia types in patients diagnosed with Mild Cognitive Impairment (MCI). Our aim was to determine profiles based on the prominent NPS in MCI patients and to explore the predictive value of these profiles on conversion to specific types of dementia. A total of 2137 MCI patients monitored in a memory clinic were included in the study. Four NPS profiles emerged (classes), which were defined by preeminent symptoms: Irritability, Apathy, Anxiety/Depression and Asymptomatic. Irritability and Apathy were predictors of conversion to dementia (HR = 1.43 and 1.56, respectively). Anxiety/depression class showed no risk effect of conversion when compared to Asymptomatic class. Irritability class appeared as the most discriminant neuropsychiatric condition to identify non-AD converters (i.e., frontotemporal dementia, vascular dementia, Parkinson's disease and dementia with Lewy Bodies). The findings revealed that consistent subgroups of MCI patients could be identified among comorbid basal NPS. The preeminent NPS showed to behave differentially on conversion to dementia, beyond AD. Therefore, NPS should be used as early diagnosis facilitators, and should also guide clinicians to detect patients with different illness trajectories in the progression of MCI.

Interaction of neuropsychiatric symptoms with APOE ε4 and conversion to dementia in MCI patients in a Memory Clinic.

To date, very few studies have been focused on the impact of the convergence of neuropsychiatric symptoms (NPS) and APOE ε4 on the conversion to dementia in patients with Mild Cognitive Impairment patients (MCI), and none has been based in a clinical setting. The objective of the study is to determine the predictive value of additive and multiplicative interactions of NPS and APOE ε4 status on the prediction of incident dementia among MCI patients monitored in a Memory Clinic. 1512 patients (aged 60 and older) with prevalent MCI were followed for a mean of 2 years. Neuropsychiatric symptoms were assessed at baseline using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models were calculated. Additive interactions for depression, apathy, anxiety, agitation, appetite, or irritability and a positive ε4 carrier status were obtained, significantly increasing the hazard ratios of incident dementia (HR range 1.3-2.03). Synergistic interactions between NPS and APOE ε4 are identified among MCI patients when predicting incident dementia. The combination of the behavioral status and the genetic trait could be considered a useful strategy to identify the most vulnerable MCI patients to dementia conversion in a Memory Clinic.

Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort.

To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aß) deposition and regional volumetric reduction in areas of interest for Alzheimer's disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. All subjects underwent an 18F-Florbetaben positron emission tomography (FBB-PET) scan to measure global standard uptake value ratio (SUVR), and a magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests significantly associated with amyloid burden, a voxel-based morphometry (VBM) analysis was carried out to explore their correlates with grey matter volume. Multiple regression analysis revealed a statistically significant association between Aß deposition and performance on one of the executive tests (the AI-SKT). Moreover, VBM analysis showed worse AI-SKT scores were related to lower volume in bilateral hippocampus and left inferior frontal regions. In conclusion, in SCD individuals, worse automatic inhibition ability has been found related to higher cerebral Aß deposition and lower volume in the hippocampus and frontal regions. Thus, our results may contribute to the early detection of AD in individuals with SCD.

Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease.

BACKGROUND: Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer's disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD. METHODS: The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, Aß-42, p-tau, and total tau levels overall and stratified by APOE genotype and with MCI to AD progression. RESULTS: Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, Aß-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aß-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with Aß-42 levels was found only in APOE ε4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort. CONCLUSIONS: Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration.

Non-Coding and Regulatory RNAs as Epigenetic Remodelers of Fatty Acid Homeostasis in Cancer.

Cancer cells commonly display metabolic fluctuations. Together with the Warburg effect and the increased glutaminolysis, alterations in lipid metabolism homeostasis have been recognized as a hallmark of cancer. Highly proliferative cancer cells upregulate de novo synthesis of fatty acids (FAs) which are required to support tumor progression by exerting multiple roles including structural cell membrane composition, regulators of the intracellular redox homeostasis, ATP synthesis, intracellular cell signaling molecules, and extracellular mediators of the tumor microenvironment. Epigenetic modifications have been shown to play a crucial role in human development, but also in the initiation and progression of complex diseases. The study of epigenetic processes could help to design new integral strategies for the prevention and treatment of metabolic disorders including cancer. Herein, we first describe the main altered intracellular fatty acid processes to support cancer initiation and progression. Next, we focus on the most important regulatory and non-coding RNAs (small noncoding RNA-sncRNAs-long non-coding RNAs-lncRNAs-and other regulatory RNAs) which may target the altered fatty acids pathway in cancer.

Dementia Care in Times of COVID-19: Experience at Fundació ACE in Barcelona, Spain.

BACKGROUND: Fundació ACE is a non-profit organization providing care based on a holistic model to persons with cognitive disorders and their families for 25 years in Barcelona, Spain. Delivering care to this vulnerable population amidst the COVID-19 pandemic has represented a major challenge to our institution. OBJECTIVE: To share our experience in adapting our model of care to the new situation to ensure continuity of care. METHODS: We detail the sequence of events and the actions taken within Fundació ACE to swiftly adapt our face-to-face model of care to one based on telemedicine consultations. We characterize individuals under follow-up by the Memory Unit from 2017 to 2019 and compare the number of weekly visits in 2020 performed before and after the lockdown was imposed. RESULTS: The total number of individuals being actively followed by Fundació ACE Memory Unit grew from 6,928 in 2017 to 8,147 in 2019. Among those newly diagnosed in 2019, most patients had mild cognitive impairment or mild dementia (42% and 25%, respectively). Weekly visits dropped by 60% following the suspension of face-to-face activity. However, by April 24 we were able to perform 78% of the visits we averaged in the weeks before confinement began. DISCUSSION: We have shown that Fundació ACE model of care has been able to successfully adapt to a health and social critical situation as COVID-19 pandemic. Overall, we were able to guarantee the continuity of care while preserving the safety of patients, families, and professionals. We also seized the opportunity to improve our model of care.

Implementing the Triangle of Wound Assessment framework to transform the care pathway for diabetic foot ulcers.

Treating patients with hard-to-heal wounds can be a daily challenge for health professionals. A systematic approach is needed to establish accurate management goals and treatment options. This should include a complete wound assessment that takes into account the wound aetiology and characteristics, as well as the patient as a whole. The Triangle of Wound Assessment is a holistic framework designed to assess and manage all wound areas-the wound bed, wound edge and periwound skin. The framework can be used to guide health professionals when evaluating a wound, setting management goals and selecting treatment options. This article describes the use of the Triangle in clinical practice. It shows how a Spanish hospital implemented the framework and how this led to its inclusion in the diabetic foot ulcer (DFU) care pathway used in the region. The article concludes with three case studies describing the clinical outcomes achieved following implementation of the Triangle when managing wounds.

Association between retinal thickness and ß-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative.

BACKGROUND: Optical coherence tomography (OCT) of the retina is a fast and easily accessible tool for the quantification of retinal structural measurements. Multiple studies show that patients with Alzheimer's disease (AD) exhibit thinning in several retinal layers compared to age-matched controls. Subjective cognitive decline (SCD) has been proposed as a risk factor for progression to AD. There is little data about retinal changes in preclinical AD and their correlation with amyloid-ß (Aß) uptake. AIMS: We investigated the association of retinal thickness quantified by OCT with Aß accumulation and conversion to mild cognitive impairment (MCI) over 24 months in individuals with SCD. METHODS: One hundred twenty-nine individuals with SCD enrolled in Fundació ACE Healthy Brain Initiative underwent comprehensive neuropsychological testing, OCT scan of the retina and florbetaben (FBB) positron emission tomography (PET) at baseline (v0) and after 24 months (v2). We assessed the association of sixteen retinal thickness measurements at baseline with FBB-PET status (+/-) and global standardize uptake value ratio (SUVR) as a continuous measure at v0 and v2 and their predictive value on clinical status change (conversion to mild cognitive impairment (MCI)) at v2. RESULTS: Mean age of the sample was 64.72 ± 7.27 years; 62.8% were females. Fifteen participants were classified as FBB-PET+ at baseline and 22 at v2. Every 1 µm of increased thickness in the inner nasal macular region conferred 8% and 6% higher probability of presenting a FBB-PET+ status at v0 (OR = 1.08, 95% CI = 1.02-1.14, p = 0.007) and v2 (OR = 1.06, 95% CI = 1.02-1.11, p = 0.004), respectively. Inner nasal macular thickness also positively correlated with global SUVR (at v0: ß = 0.23, p = 0.004; at v2: ß = 0.26, p = 0.001). No retinal measurements were associated to conversion to MCI over 24 months. CONCLUSIONS: Subtle retinal thickness changes in the macular region are already present in SCD and correlate with Aß uptake.

A computerized version of the Short Form of the Face-Name Associative Memory Exam (FACEmemory®) for the early detection of Alzheimer's disease.

BACKGROUND: Computerized neuropsychological tests for early detection of Alzheimer's disease (AD) have attracted increasing interest. Memory for faces and proper names is a complex task because its association is arbitrary. It implicates associative occipito-temporal cerebral regions, which are disrupted in AD. The short form of the Face-Name Associative Memory Exam (FNAME-12), developed to detect preclinical and prodromal AD, asks individuals to learn the names and occupations associated with 12 faces. The current work advances this field by using voice recognition and touchscreen response format. The purpose of this study is to create the first self-administered episodic memory test, FACEmemory®, by adapting the FNAME-12 for tablet use with voice recognition, touchscreen answers, and automatic scoring. The test was minimally supervised by a psychologist to avoid technological problems during execution and scored manually to assess the reliability of the automatic scoring. The aims of the present study were (1) to determine whether FACEmemory® is a sensitive tool for the detection of cognitive impairment, (2) to examine whether performances on FACEmemory® are correlated with those on the S-FNAME (paper-and-pencil version with 16 images), and (3) to determine whether performances on FACEmemory® are related to AD biomarkers in the cerebrospinal fluid (CSF) (Aß42, p-tau, and Aß42/p-tau ratio). METHODS: FACEmemory® was completed by 154 cognitively healthy (CH) individuals and 122 subjects with mild cognitive impairment, of whom 61 were non-amnestic (naMCI) and 61 amnestic (aMCI). A subsample of 65 individuals completed the S-FNAME, and 65 subjects received lumbar punctures. RESULTS: Performance on FACEmemory® was progressively worse from CH to the naMCI and aMCI groups. A cutoff of 31.5 in total FACEmemory® obtained 80.5% and 80.3% sensitivity and specificity values, respectively, for discriminating between CH and aMCI. Automatically corrected FACEmemory® scores were highly correlated with the manually corrected ones. FACEmemory® scores and AD CSF biomarker levels were significantly correlated as well, mainly in the aMCI group. CONCLUSIONS: FACEmemory® may be a promising memory prescreening tool for detecting subtle memory deficits related to AD. Our findings suggest FACEmemory® performance provides a useful gradation of impairment from normal aging to aMCI, and it is related to CSF AD biomarkers.