An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Is REBOA the Last Card to Control a Massive Gastrointestinal Bleeding?

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potential tool for the management of massive gastrointestinal bleeding (MGB). This study aims to describe the experience of the use of REBOA as adjunctive therapy in patients with MGB and to evaluate its effectiveness. METHODS: Serial cases of patients with hemorrhagic shock secondary to MGB in whom REBOA was placed were collected. Patient demographics, bleeding severity, etiology, management, and clinical outcomes were recorded. RESULTS: Between 2017 and 2020, five cases were analyzed. All patients had a severe gastrointestinal bleeding (Glasgow Blatchford Bleeding Score range 12-17; Clinical Rockal Score range 5-9). The etiologies of MGB were perforated gastric or duodenal ulcers, esophageal varices, and vascular lesions. Systolic blood pressure increased after REBOA placement and total occlusion time was 25-60 min. REBOA provided temporary hemorrhage control in all cases and allowed additional hemostatic maneuvers to be performed. Three patients survived more than 24 h. All patients died in index hospitalization. The main cause of death was related to hemorrhagic shock. CONCLUSIONS: Endovascular aortic occlusion can work as a bridge to further resuscitation and attempts at hemostasis in patients with MGB. REBOA provides hemodynamic support and may be used simultaneously with other hemostatic maneuvers, facilitating definitive hemorrhage control.

When Maturation is Not Linear: Brain Oscillatory Activity in the Process of Aging as Measured by Electrophysiology.

Changes in brain oscillatory activity are commonly used as biomarkers both in cognitive neuroscience and in neuropsychiatric conditions. However, little is known about how its profile changes across maturation. Here we use regression models to characterize magnetoencephalography power changes within classical frequency bands in a sample of 792 healthy participants, covering the range 13 to 80 years old. Our findings unveil complex, non-linear power trajectories that defy the traditional linear paradigm, with notable cortical region variations. Interestingly, slow wave activity increases correlate with improved cognitive performance throughout life and larger gray matter volume in the elderly. Conversely, fast wave activity diminishes in adulthood. Elevated low-frequency activity during aging, traditionally seen as compensatory, may also signify neural deterioration. This dual interpretation, highlighted by our study, reveals the intricate dynamics between brain oscillations, cognitive performance, and aging. It advances our understanding of neurodevelopment and aging by emphasizing the regional specificity and complexity of brain rhythm changes, with implications for cognitive and structural integrity.

Tic-Tac: A Translational Approach in Mechanisms Associated with Irregular Heartbeat and Sinus Rhythm Restoration in Atrial Fibrillation Patients.

Atrial fibrillation (AF) is a prevalent cardiac condition predominantly affecting older adults, characterized by irregular heartbeat rhythm. The condition often leads to significant disability and increased mortality rates. Traditionally, two therapeutic strategies have been employed for its treatment: heart rate control and rhythm control. Recent clinical studies have emphasized the critical role of early restoration of sinus rhythm in improving patient outcomes. The persistence of the irregular rhythm allows for the progression and structural remodeling of the atria, eventually leading to irreversible stages, as observed clinically when AF becomes permanent. Cardioversion to sinus rhythm alters this progression pattern through mechanisms that are still being studied. In this review, we provide an in-depth analysis of the pathophysiological mechanisms responsible for maintaining AF and how they are modified during sinus rhythm restoration using existing therapeutic strategies at different stages of clinical investigation. Moreover, we explore potential future therapeutic approaches, including the promising prospect of gene therapy.

Impact of Public Health Policies on Alcohol-Associated Liver Disease in Latin America: An Ecological Multinational Study.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin America, yet the impact of public health policies (PHP) on liver disease is unknown. We aimed to assess the association between alcohol PHP and deaths due to ALD in Latin American countries. APPROACH AND RESULTS: We performed an ecological multinational study including 20 countries in Latin America (628,466,088 inhabitants). We obtained country-level sociodemographic information from the World Bank Open Data source. Alcohol-related PHP data for countries were obtained from the World Health Organization Global Information System of Alcohol and Health. We constructed generalized linear models to assess the association between the number of PHP (in 2010) and health outcomes (in 2016). In Latin America, the prevalence of obesity was 27% and 26.1% among male and female populations, respectively. The estimated alcohol per capita consumption among the population at 15 years old or older was 6.8 L of pure alcohol (5.6 recorded and 1.2 unrecorded). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of male and 40.0% of female populations. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were limiting drinking age (95%), tax regulations (90%), drunk-driving policies and countermeasures (90%), and government monitoring systems and community support (90%). A higher number of PHP was associated with a lower ALD mortality (PR, 0.76; 95% CI, 0.61-0.93; P = 0.009), lower AUD prevalence (PR, 0.80; 95% CI, 0.65-0.99; P = 0.045), and lower alcohol-attributable road traffic deaths (PR, 0.81; 95% CI, 0.65-1.00; P = 0.051). CONCLUSIONS: Our study indicates that in Latin America, countries with higher number of PHP have lower mortality due to ALD, lower prevalence of AUD, and lower alcohol-attributable road traffic mortality.

"It's a beer!": Brain functional hyperconnectivity during processing of alcohol-related images in young binge drinkers.

Alcohol attentional bias has been pointed as a major marker of alcohol misuse. Recent evidence has revealed that brain functional connectivity (FC) may be a valuable index of the brain networks' integrity in young binge drinkers (BDs). However, there is no study to date examining the FC networks linked to the processing of alcohol-related images in this population. The present study aimed to explore the FC signatures underlying alcohol attention bias in young BDs. Thus, electroencephalographic (EEG) activity was recorded in 54 college students (55.5% females; 27 non/low-drinkers and 27 BDs) while performing a visual alcohol cue-reactivity task. We evaluated whole-brain FC profiles during the processing of alcoholic and non-alcoholic cues, as well as their potential relationship with craving and severity of alcohol use. Results showed that, at the behavioural level, BDs rated alcohol-related images as more pleasant/attractive than non/low-drinkers. Furthermore, at the electrophysiological level, BDs exhibited increased beta-band FC-particularly in the fronto-parieto-occipital network-when processing alcoholic cues. Conversely, they displayed reduced theta-band FC relatively to non/low-drinkers for non-alcoholic images. These hyper-/hypo-connectivity patterns were associated with higher alcohol craving levels. Findings are congruent with previous neurofunctional studies reporting an attentional bias towards alcohol-related information in BDs. These results may have important clinical implications as this neural reactivity to alcoholic cues may contribute to the maintenance and/or escalation of the drinking pattern. Finally, the present study constitutes the first evidence showing that FC networks may be a sensitive indicator to alcohol attentional bias in BDs.

Alcohol-related stimuli modulate functional connectivity during response inhibition in young binge drinkers.

Binge drinking is a pattern of intermittent excessive alcohol consumption that is highly prevalent in young people. Neurocognitive dual-process models have described substance abuse and adolescence risk behaviours as the result of an imbalance between an overactivated affective-automatic system (related to motivational processing) and damaged and/or immature reflective system (related to cognitive control abilities). Previous studies have evaluated the reflective system of binge drinkers (BDs) through neutral response inhibition tasks and have reported anomalies in theta (4-8 Hz) and beta (12-30 Hz) bands. The present study aimed to investigate the influence of the motivational value of alcohol-related stimuli on brain functional networks devoted to response inhibition in young BDs. Sixty eight BDs and 78 control participants performed a beverage Go/NoGo task while undergoing electrophysiological recording. Whole cortical brain functional connectivity (FC) was evaluated during successful response inhibition trials (NoGo). BDs exhibited fast-beta and theta hyperconnectivity in regions related to cognitive control. These responses were modulated differently depending on the motivational content of the stimuli. The increased salience of alcohol-related stimuli may lead to overactivation of the affective-automatic system in BDs, and compensatory neural resources of the reflective system will thus be required during response inhibition. In BDs, inhibition of the response to alcohol stimuli may require higher theta FC to facilitate integration of information related to the task goal (withholding a response), while during inhibition of the response to no-alcoholic stimuli, higher fast-beta FC would allow to apply top-down inhibitory control of the information related to the prepotent response.

Electrophysiological resting-state hyperconnectivity and poorer behavioural regulation as predisposing profiles of adolescent binge drinking.

Adolescent Binge Drinking (BD) has become an increasing health and social concern, with detrimental consequences for brain development and functional integrity. However, research on neurophysiological and neuropsychological traits predisposing to BD are limited at this time. In this work, we conducted a 2-year longitudinal magnetoencephalography (MEG) study over a cohort of initially alcohol-naïve adolescents with the purpose of exploring anomalies in resting-state electrophysiological networks, impulsivity, sensation-seeking, and dysexecutive behaviour able to predict future BD patterns. In a sample of 67 alcohol-naïve adolescents (age = 14.5 ± 0.9), we measured resting-state activity using MEG. Additionally, we evaluated their neuropsychological traits using self-report ecological scales (BIS-11, SSS-V, BDEFS, BRIEF-SR and DEX). In a second evaluation, 2 years later, we measured participant's alcohol consumption, sub-dividing the original sample in two groups: future binge drinkers (22 individuals, age 14.6 ± 0.8; eight females) and future light/no drinkers (17 individuals, age 14.5 ± 0.8; eight females). Then, we searched for differences predating alcohol BD intake. We found abnormalities in MEG resting state, in a form of gamma band hyperconnectivity, in those adolescents who transitioned into BD years later. Furthermore, they showed higher impulsivity, dysexecutive behaviours and sensation seeking, positively correlated with functional connectivity (FC). Sensation seeking and impulsivity mainly predicted BD severity in the future, while the relationship between dysexecutive trait and FC with future BD was mediated by sensation seeking. These findings shed light to electrophysiological and neuropsychological traits of vulnerability towards alcohol consumption. We hypothesise that these differences may rely on divergent neurobiological development of inhibitory neurotransmission pathways and executive prefrontal circuits.

[Efficacy of a standardized and simplified strategy for the treatment of high blood pressure in Chile: the HEARTS Initiative in the AmericasEficácia de uma estratégia padronizada e simplificada para o tratamento da hipertensão arterial no Chile: a iniciativa HEARTS nas Américas]. / Eficacia de una estrategia estandarizada y simplificada para tratamiento de la hipertensión arterial en Chile: la Iniciativa HEARTS en las Américas.

Objective: To evaluate the effectiveness of a standardized and simplified protocol based on the technical pillars of the HEARTS Initiative for the control of hypertensive patients in the Cardiovascular Health Program at the first level of care in Chile. Methods: Longitudinal observational study (historical cohort) in two family health centers at the first level of care in Santiago. The control of blood pressure in hypertensive adults using a standardized and simplified protocol was compared to the usual protocol based on national guidelines. Innovations in the standardized protocol included changes in how the health team is coordinated, initiation of pharmacological treatment immediately after confirmed diagnosis, standardized pharmacological treatment with a combination of at least two or three antihypertensive drugs taken daily in a single tablet. Follow-up was conducted after one year to assess the percentage of adherence to treatment and achievement of blood pressure control targets (< 140/90 mmHg). Results: A total of 1490 patients were evaluated: 562 who followed the standardized and simplified protocol, and 928 who were treated with the usual protocol (family health centers: 650; family health centers: 278). After one year, patients in the standardized and simplified protocol group had a higher proportion of adherence to blood pressure control targets (65% versus 37% and 41%, p<0.001) and higher adherence to treatment compared to those following the usual protocol (71% versus 18% and 23%, p<0.001). Conclusions: The results show that the standardized and simplified protocol is more effective than the usual protocol in controlling arterial hypertension in patients undergoing treatment at the first level of care in Chile. Its implementation at the national level could contribute to a decrease in major cardiovascular events.

Objetivo: Avaliar a eficácia de um protocolo padronizado e simplificado, com base nos pilares técnicos da iniciativa HEARTS, para o controle de pacientes com hipertensão arterial do Programa de Saúde Cardiovascular na atenção primária à saúde do Chile. Métodos: Estudo observacional longitudinal (coorte histórica) em 2 centros de atenção primária de saúde da família em Santiago, que comparou o controle da pressão arterial em adultos com hipertensão, atingido com o protocolo padronizado e simplificado, versus o protocolo habitual, de acordo com as diretrizes nacionais. As inovações do protocolo padronizado incluíram mudanças na coordenação da equipe de saúde, início do tratamento farmacológico imediatamente após a confirmação do diagnóstico e tratamento farmacológico padronizado com associação de pelo menos 2 ou 3 anti-hipertensivos em um único comprimido, tomados uma vez ao dia. O acompanhamento foi realizado por 1 ano para avaliar o percentual de adesão ao tratamento e o cumprimento das metas de controle da pressão arterial (menor que 140/90 mmHg). Resultados: Foram avaliados 1.490 pacientes: 562 que utilizaram o protocolo padronizado e simplificado e 928 que foram tratados com o protocolo habitual (unidade de saúde da família 1: 650, unidade de saúde da família 2: 278). Em 1 ano de seguimento, os pacientes do grupo do protocolo padronizado e simplificado apresentaram maior proporção de cumprimento das metas de controle da pressão arterial (65% versus 37% e 41%, p<0,001) e maior percentual de adesão ao tratamento, em comparação com aqueles que utilizaram o protocolo habitual (71% versus 18% e 23%, p<0,001). Conclusões: Os resultados mostram que o protocolo padronizado e simplificado é mais eficaz que o protocolo habitual no controle da hipertensão arterial em pacientes que estão em tratamento na atenção primária do Chile. Sua implementação no nível nacional poderia contribuir para a redução de eventos cardiovasculares maiores.

[Effectiveness of regional citrate anticoagulation in continuous renal replacement therapy]. / Efectividad de anticoagulación regional con citrato en terapia de reemplazo renal continua.

BACKGROUND: Anticoagulation in continuous renal replacement therapy (CRRT) is essential to counteract the coagulation cascade activation, induced by the dialysis circuit. Heparin is the most widely used anticoagulant, followed by regional citrate anticoagulation (RCA). AIM: To determine the effectiveness and safety of anticoagulant treatment with citrate in CRRT. MATERIAL AND METHODS: Retrospective study of adults in CRRT hospitalized between the years 2014 and 2020 in critical units, who required change to RCA according to established protocols. RESULTS: We studied 24 patients aged 63 ± 13 years (12 females). The reasons for admission were acute kidney injury (AKI) in 80% and stage 5 chronic kidney disease in 20%. The indication of RCA in 75% of patients was by coagulation of more than 3 circuits in 24 hours. The duration of the circuit in RCA was 18.5 ± 4.8 hours versus 11.9 ± 4.9 hours with heparin (p < 0.0001). There were 19 mild complications that did not affect the RCA. CONCLUSIONS: RCA is feasible to perform, it is a safe and efficient procedure if it is protocolized, allowing a longer duration of the dialysis circuit.

Long-term outcome of early steroid withdrawal in pediatric renal transplantation.

BACKGROUND: Steroid use in renal transplant is related to multiple adverse effects. Long-term effects of early withdrawal steroids in pediatric renal transplant were assessed. METHODS: Renal transplant children with low immunological risk treated on basiliximab, tacrolimus, and mycophenolate with steroid withdrawal or steroid control were evaluated between 2003 and 2019. Clinical variables, treatment adherence, acute rejection, graft loss, and death were analyzed through hazard ratios, and Kaplan-Meier and multivariate analyses. RESULTS: The study included 152 patients, 71.1% steroid withdrawal, mean follow-up 8.5 years, 64.5% structural abnormalities, and 81.6% deceased donor. At 12 years of transplant, event-free survival analysis for graft loss or death showed no significant difference between steroid withdrawal and control steroid treatment (85.9% vs. 80.4%, p = .36) nor in acute rejection at 10 years (18.5% vs. 20.5%, p = .78) or in donor-specific antibody appearance (19.6% vs. 21.4%, p = .98). Delta height Z-score was increased in the steroid withdrawal group (p < .01). The main predictor of graft loss or death was non-adherence to treatment (p = .001; OR: 17.5 [3.3-90.9]). CONCLUSIONS: Steroid withdrawal therapy was effective and safe for low-risk pediatric renal transplant in long-term evaluation. Non-adherence was the main predictor of graft loss or death.

Damage Control Surgery may be a Safe Option for Severe Non-Trauma Peritonitis Management: Proposal of a New Decision-Making Algorithm.

BACKGROUND: Damage control surgery (DCS) has emerged as a new option in the management of non-traumatic peritonitis patients to increase survival in critically ill patients. The purpose of this study was to compare DCS with conventional strategy (anastomosis/ostomies in the index laparotomy) for severe non-traumatic peritonitis regarding postoperative complications, ostomy rate, and mortality and to propose a useful algorithm in the clinical practice. METHODS: Patients who underwent an urgent laparotomy for non-trauma peritonitis at a single level I trauma center in Colombia between January 2003 and December 2018, were retrospectively included. We compared patients who had DCS management versus definitive initial surgical management (DISM) group. We evaluated clinical outcomes and morbidities among groups. RESULTS: 290 patients were included; 81 patients were treated with DCS and 209 patients underwent DISM. Patients treated with DCS had a worse critical status before surgery with higher SOFA score [median, DCS group: 5 (IQR: 3-8) vs. DISM group: 3 (IQR: 1-6), p < 0.001]. The length of hospital stay and overall mortality rate of DCS group were not significant statistical differences with DISM group. Complications rate related to primary anastomosis or primary ostomy was similar. There is not difference in ostomy rate among groups. At multivariate analysis, SOFA > 6 points and APACHE-II > 20 points correlated with a higher probability of DCS. CONCLUSION: DCS in severe non-trauma peritonitis patients is feasible and safe as surgical strategy management without increasing mortality, length hospital of stay, or complications. DCS principles might be applied in the non-trauma scenarios without increase the stoma rate.

Prospective Latin American cohort evaluating outcomes of patients with COVID-19 and abnormal liver tests on admission.

INTRODUCTION & OBJECTIVES: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. MATERIALS & METHODS: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. RESULTS: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. CONCLUSIONS: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection.

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.

Electrophysiological Brain Changes Associated With Cognitive Improvement in a Pediatric Attention Deficit Hyperactivity Disorder Digital Artificial Intelligence-Driven Intervention: Randomized Controlled Trial.

BACKGROUND: Cognitive stimulation therapy appears to show promising results in the rehabilitation of impaired cognitive processes in attention deficit hyperactivity disorder. OBJECTIVE: Encouraged by this evidence and the ever-increasing use of technology and artificial intelligence for therapeutic purposes, we examined whether cognitive stimulation therapy implemented on a mobile device and controlled by an artificial intelligence engine can be effective in the neurocognitive rehabilitation of these patients. METHODS: In this randomized study, 29 child participants (25 males) underwent training with a smart, digital, cognitive stimulation program (KAD_SCL_01) or with 3 commercial video games for 12 weeks, 3 days a week, 15 minutes a day. Participants completed a neuropsychological assessment and a preintervention and postintervention magnetoencephalography study in a resting state with their eyes closed. In addition, information on clinical symptoms was collected from the child´s legal guardians. RESULTS: In line with our main hypothesis, we found evidence that smart, digital, cognitive treatment results in improvements in inhibitory control performance. Improvements were also found in visuospatial working memory performance and in the cognitive flexibility, working memory, and behavior and general executive functioning behavioral clinical indexes in this group of participants. Finally, the improvements found in inhibitory control were related to increases in alpha-band power in all participants in the posterior regions, including 2 default mode network regions of the interest: the bilateral precuneus and the bilateral posterior cingulate cortex. However, only the participants who underwent cognitive stimulation intervention (KAD_SCL_01) showed a significant increase in this relationship. CONCLUSIONS: The results seem to indicate that smart, digital treatment can be effective in the inhibitory control and visuospatial working memory rehabilitation in patients with attention deficit hyperactivity disorder. Furthermore, the relation of the inhibitory control with alpha-band power changes could mean that these changes are a product of plasticity mechanisms or changes in the neuromodulatory dynamics. TRIAL REGISTRATION: ISRCTN Registry ISRCTN71041318; https://www.isrctn.com/ISRCTN71041318.

Attended Automated Office Blood Pressure Measurement Versus Ambulatory Blood Pressure Monitoring in a Primary Healthcare Setting in Chile.

OBJECTIVES: As part of the HEARTS in the Americas initiative, Chilean primary healthcare centers have implemented novel hypertension management strategies, including new diagnostic approaches. This study evaluated the concordance between attended automated office blood pressure (AOBP) measurements with an oscillometric device and ambulatory blood pressure monitoring (ABPM). METHODS: This was an observational cohort study to evaluate and compare attended AOBP and ABPM for the diagnosis of hypertension in adults in a primary healthcare setting. RESULTS: The study evaluated 309 participants (54.2 ± 15.7 years; 50.5% male) from four primary healthcare centers in Santiago, Chile. Attended AOBP measurements were obtained at the clinic on two separate days, followed by ABPM. AOBP values indicated that 69.6% of patients had a systolic blood pressure (SBP) of ≥140 mm Hg and 34.6% had a diastolic blood pressure (DBP) of ≥90 mm Hg. A total of 83.5% had hypertension, 45.3% had high SBP, and 56.0% had high DBP. ABPM values indicated that 65.0% of patients had hypertension. The combined AOBP and ABPM analysis showed that 57.0% of patients had sustained hypertension, 26.5% had white coat hypertension, 8.1% had masked hypertension, and 8.4% were normotensive. The concordance between AOBP and ABPM (κ coefficient) was low (κ = 0.133; 95% confidence interval 0.028-0.237). The comparison of AOBP and ABPM measurements (Bland-Altman plots and bias calculations) showed an important bias in BP as measured using the AOBP method, especially for SBP (13.7 ± 11.6, 95% confidence interval -9.1 to 36.5). CONCLUSIONS: Attended AOBP alone may not be sufficient for adequate classification, diagnosis, and management of hypertension in Chile or other countries with similar demographics.

[Rhabdomyolysis as the presentation form of COVID-19 infection. Report of one case]. / Rabdomiólisis como presentación inicial de COVID-19. Caso Clínico.

COVID-19 infection causes a systemic inflammatory response, which mainly presents as a febrile syndrome with respiratory involvement. We report a 37-year-old male who consulted for myalgia, nausea and epigastric pain lasting three days. On admission, he had crepitations at the lung bases. The initial laboratory showed a creatine kinase of 62,768 U/L, a LDH of 1,110 IU/L, a creatinine a 2.1 mg/dL, an aspartate aminotransferase of 1,347 IU/L, a D-dimer of 1,140 ng/mL, a ferritin of 1,201 ng/mL and a lymphocyte count of 810 cells/mm3. The chest CT scan was compatible with multifocal pneumonia, suggesting a COVID-19 infection. COVID-19 PCR was positive. The patient was managed with hydration, sodium bicarbonate, ceftriaxone, and azithromycin, with a good clinical response.

[Hypophosphatemia induced by carboxymaltose iron and imatinib. Report of two cases]. / Hipofosfatemia inducida por drogas: fierro carboximaltosa e imatinib. Casos clínicos.

Hypophosphatemia is a relatively frequent and a potentially serious adverse drug effect. Clinically it is characterized by bone pain and muscle weakness. There are several mechanisms by which a drug can induce hypophosphatemia and they can be classified according to whether or not they are mediated by an excess of Fibroblast Growth Factor 23 (FGF23). We report two patients with the condition: (i) A 49-year-old woman with Chronic Myeloid Leukemia (CML) and gastric sleeve surgery at 46 years of age. After receiving intravenous carboxymaltose iron in one occasion due to refractory anemia, she developed symptomatic hypophosphatemia. Urinary phosphate losses associated with high FGF23 levels were confirmed. Plasma phosphate returned to normal values 90 days after the iron administration. (ii) A 40-year-old man with a history of CML in whom imatinib was started. He developed symptomatic hypophosphatemia due to non FGF23-mediated hyperphosphaturia. As treatment with imatinib could not be interrupted, hypophosphatemia and its symptoms resolved with oral phosphate intake. These cases illustrate the importance of recognizing and treating drug-induced hypophosphatemia in a timely manner, and thus avoid the morbidity associated with this entity.

Erythropoietin induces bone marrow and plasma fibroblast growth factor 23 during acute kidney injury.

It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI. We found that erythroid progenitor cells of bone marrow express FGF23. Erythropoietin increased FGF23 expression in vivo and in bone marrow cell cultures via the homodimeric erythropoietin receptor. In experimental AKI secondary to hemorrhagic shock or sepsis in rodents, there was a rapid increase of plasma erythropoietin, and an induction of bone marrow FGF23 expression together with a rapid increase of circulating FGF23. Blockade of the erythropoietin receptor fully prevented the induction of bone marrow FGF23 and partially suppressed the increase of circulating FGF23. Finally, there was an early increase of both circulating FGF23 and erythropoietin in a cohort of patients with severe sepsis who developed AKI within 48 hours of admission. Thus, increases in plasma erythropoietin and erythropoietin receptor activation are mechanisms implicated in the increase of plasma FGF23 in AKI.

Cost-effectiveness analysis of interventions for prevention of invasive aspergillosis among leukemia patients during hospital construction activities.

OBJECTIVES: Invasive Aspergillosis (IA) is a serious problem among hematological patients and it is associated with high mortality. This situation can worsen at times of hospital construction, however there are several preventive measures available. This work aims to define the cost-effectiveness of some of these interventions. PATIENTS AND METHODS: A decision tree model was used, it was divided into four arms according to each 1 of the interventions performed. A cost-effectiveness incremental analysis comparing environmental control measures, high efficiency particulate absorption (HEPA) filter installation and prophylaxis with posaconazole was done. Probabilistic and deterministic sensitivity analyses were also carried out. RESULTS: Among 86 patients with 175 hospitalization episodes, the incidence of IA with environmental protection measures, antifungal prophylaxis and hospitalization in rooms with HEPA filters was 14.4%, 6.3% and 0%, respectively. An Incremental Cost Effectiveness Ratio analysis was performed and it was found that HEPA filtered rooms and environmental protection measures are cost saving interventions when compared with posaconazole prophylaxis (-$2665 vs -$4073 vs $42 531 US dollars, respectively) for IA episode prevented. CONCLUSION: The isolation of inpatients with acute leukemia during hospital construction periods in HEPA filtered rooms could reduce the incidence of IA and might be a cost-effective prevention strategy.