Can biochemical tracers reveal ontogenetic trophic shift and individual prey selection in white sharks from Guadalupe Island, Northeast Pacific?

Refining the role of apex predators in marine food webs is a necessary step in predicting the consequences of their global decline under the footprint of fishing activities. White sharks (Carcharodon carcharias) are vulnerable predators, performing large migrations and able to forage on a variety of prey in different habitats. In the Northeast Pacific, juvenile and adult white sharks are found seasonally at the same aggregation sites, such as Guadalupe Island off Mexico. While adults are thought to target local pinniped colonies, very few predator-prey interactions have been documented and the diet of juveniles in this area remains poorly understood. Here we used carbon/nitrogen stable isotopes and fatty acids to characterize the trophic ecology of white sharks at Guadalupe Island. In contrast to the ontogenetic trophic shift paradigm, we detected no influence of size on muscle stable isotope and fatty acid composition, revealing no significant dietary variation between juvenile and adult sharks. Stable isotopes did not allow definitive conclusions to be drawn regarding the diet of white sharks at Guadalupe Island, due to significant variability in the contribution of different potential prey depending on the trophic discrimination factors used. However, most sharks were rich in polyunsaturated fatty acids (such as long-chain omega 3), suggesting a local diet of mainly pelagic prey (potentially large fish or cephalopods). A few individuals appeared to show recent consumption of pinnipeds, with higher proportions of saturated and monounsaturated fatty acids. These individual differences in fatty acid composition could reflect an ecological trade-off between consumption of prey rich in fat (marine mammals) versus prey rich in polyunsaturated fatty acids (pelagic prey), respectively meeting the energetic and physiological needs of white sharks. Although ontogenetic trophic changes were not able to be discerned, our results provide new insights into the physiological drivers of predator-prey interactions, which can benefit the definition of conservation strategies in a changing ocean.

Differential Effects of a Telemonitoring Platform in the Development of Chemotherapy-Associated Toxicity: A Randomized Trial Protocol.

Chemotherapy requires careful monitoring, but traditional follow-up approaches face significant challenges that were highlighted by the COVID-19 pandemic. Hence, exploration into telemonitoring as an alternative emerged. The objective is to assess the impact of a telemonitoring platform that provides clinical data to physicians overseeing solid tumor patients, aiming to enhance the care experience. The methodology outlines a parallel-group randomized clinical trial involving recently diagnosed patients with solid carcinomas preparing for curative intent chemotherapy. Eligible adult patients diagnosed with specific carcinoma types and proficient in Spanish, possessing smartphones, will be invited to participate. They will be randomized using concealed allocation sequences into two groups: one utilizing a specialized smartphone application called Contigo for monitoring chemotherapy toxicity symptoms and accessing educational content, while the other receives standard care. Primary outcome assessment involves patient experience during chemotherapy using a standardized questionnaire. Secondary outcomes include evaluating severe chemotherapy-associated toxicity, assessing quality of life, and determining user satisfaction with the application. The research will adhere to intention-to-treat principles. This study has been registered at ClinicalTrials.gov (NCT06077123).

Effects on Quality of Life of a Telemonitoring Platform amongst Patients with Cancer (EQUALITE): A Randomized Trial Protocol.

Cancer, a pervasive global health challenge, necessitates chemotherapy or radiotherapy treatments for many prevalent forms. However, traditional follow-up approaches encounter limitations, exacerbated by the recent COVID-19 pandemic. Consequently, telemonitoring has emerged as a promising solution, although its clinical implementation lacks comprehensive evidence. This report depicts the methodology of a randomized trial which aims to investigate whether leveraging a smartphone app called Contigo for disease monitoring enhances self-reported quality of life among patients with various solid cancers compared to standard care. Secondary objectives encompass evaluating the app's impact on depressive symptoms and assessing adherence to in-person appointments. Randomization will be performed independently using an allocation sequence that will be kept concealed from clinical investigators. Contigo offers two primary functions: monitoring cancer patients' progress and providing educational content to assist patients in managing common clinical situations related to their disease. The study will assess outcomes such as quality of life changes and depressive symptom development using validated scales, and adherence to in-person appointments. Specific scales include the EuroQol Group's EQ-5D questionnaire and the Patient Health Questionnaire (PHQ-9). We hypothesize that the use of Contigo will assist and empower patients receiving cancer treatment, which will translate to better quality of life scores and a reduced incidence of depressive symptoms. All analyses will be undertaken with the intention-to-treat principle by a statistician unaware of treatment allocation. This trial is registered in ClinicalTrials under the registration number NCT06086990.

Effects of internet-based telemonitoring platforms on the quality of life of oncologic patients: A systematic literature review protocol.

INTRODUCTION: Telemonitoring involves the transmission of clinical information through digital means, including internet-connected devices such as smartphones, health tracking apps and video conferencing platforms. This strategy could provide a viable alternative to facilitate follow-up in several conditions, including cancer. OBJECTIVES: To synthesise the available evidence on the effectiveness of internet-based telemonitoring platforms amongst oncological patients. Relevant endpoints include overall quality of life, the ability to detect postoperative complications, severe toxicity reactions attributable to chemotherapy, reducing the frequency of hospitalisations, emergency department visits and mortality. METHODS: A systematic review of published and unpublished randomised and controlled studies will be carried out. Iterative searches in PubMED/MEDLINE, EMBASE, Epistemonikos, LILACS, and Cochrane CENTRAL repositories from January 2000 to January 2023 will be conducted. Grey literature repositories, such as Clinicaltrials, BioRxiv and MedRxiv will be searched as well. The Cochrane risk of bias tool will be used to assess the quality of the eligible studies. If possible, a meta-analysis based on the random-effects model will be conducted to evaluate changes in any of the aforementioned outcomes. Heterogeneity will be assessed with Cochrane's Q and I2 statistics. Its exploration will be carried out using subgroup and sensitivity analyses. Relevant subgroups include the proportion of elderly patients in each study, characteristics of each platform, study type, type of funding and moment of conduction (i.e. before or after the COVID-19 pandemic). Publication bias will be assessed using funnel plots and Egger's test. REGISTRATION: This systematic review protocol is registered in PROSPERO. Its registration number is CRD42023412705.

How can we improve the quality of health care in hospital attendance of medically complex children? / ¿Cómo podemos mejorar la calidad de la atención hospitalaria de los pacientes crónicos complejos en pediatría?

Hospital care of medically complex children (MCC) is increasing, although its real prevalence in Spain is unknown. OBJECTIVE: to analyze hospital admissions and outpatient follow-up of MCC in order to identify strategies to improve the quality of care of MCC. PATIENTS AND METHOD: An analytical, observational, and retrospective study was carried out. We included MCC who were admitted to Pediatric Hospitalization in the last 5 years, in a tertiary hospital without a specific unit for MCC. Clinical data related to their underlying pathology, outpatient visits, and hospital admissions were collected. A multivariate study was carried out to describe risk factors of the need for technological support and to predict prolonged admissions and the hospital consultation rate. RESULTS: 99 MCC (55.6% males) aged 3.9 (2-8) years were included. 41.4% of MCC required technological support at home and presented the highest number of comorbidities, hospital admissions, and care by different specialists (p < 0.01). Older MCC (p < 0.01) with underlying digestive disease (p < 0.04) and respiratory comorbidity (p < 0.04) presented a longer mean hospital stays. Younger patients with more admissions, longer average stay, and a lack of follow-up by the link nurse were associated with a greater number of annual consultations (p < 0.05). CONCLUSIONS: MCC require a high number of annual consultations and have long hospital stays. The creation of specialized consultations for MCC, multidisciplinary care, and the participation of the link nurse are strategies to improve the quality of care for MCC in hospitals without specific MCC units.

Oxidative damage associated with exposure to heavy metals present in topsoils in central Chile.

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations. We took blood samples from 140 adults living in sites with high concentrations of heavy metals in the soil and compared them with blood samples from 140 adults living in areas with normal heavy metal concentrations. We assessed lipid peroxidation, damage to genetic material, and Total Antioxidant Capacity in these blood samples. Our results indicate an association between oxidative damage and heavy metal exposure, where the inhabitants living in exposed areas have a higher level of DNA damage compared with those living in control areas. Given that DNA damage is one of the main factors in carcinogenesis, these results are of interest, both for public health and for public policies aimed at limiting human exposure to environmental pollution.

Identification of Radiomic Signatures in Brain MRI Sequences T1 and T2 That Differentiate Tumor Regions of Midline Gliomas with H3.3K27M Mutation.

BACKGROUND: Radiomics refers to the acquisition of traces of quantitative features that are usually non-perceptible to human vision and are obtained from different imaging techniques and subsequently transformed into high-dimensional data. Diffuse midline gliomas (DMG) represent approximately 20% of pediatric CNS tumors, with a median survival of less than one year after diagnosis. We aimed to identify which radiomics can discriminate DMG tumor regions (viable tumor and peritumoral edema) from equivalent midline normal tissue (EMNT) in patients with the positive H3.F3K27M mutation, which is associated with a worse prognosis. PATIENTS AND METHODS: This was a retrospective study. From a database of 126 DMG patients (children, adolescents, and young adults), only 12 had H3.3K27M mutation and available brain magnetic resonance DICOM file. The MRI T1 post-gadolinium and T2 sequences were uploaded to LIFEx software to post-process and extract radiomic features. Statistical analysis included normal distribution tests and the Mann-Whitney U test performed using IBM SPSS® (Version 27.0.0.1, International Business Machines Corp., Armonk, NY, USA), considering a significant statistical p-value ≤ 0.05. RESULTS: EMNT vs. Tumor: From the T1 sequence 10 radiomics were identified, and 14 radiomics from the T2 sequence, but only one radiomic identified viable tumors in both sequences (p < 0.05) (DISCRETIZED_Q1). Peritumoral edema vs. EMNT: From the T1 sequence, five radiomics were identified, and four radiomics from the T2 sequence. However, four radiomics could discriminate peritumoral edema in both sequences (p < 0.05) (CONVENTIONAL_Kurtosis, CONVENTIONAL_ExcessKurtosis, DISCRETIZED_Kurtosis, and DISCRETIZED_ExcessKurtosis). There were no radiomics useful for distinguishing tumor tissue from peritumoral edema in both sequences. CONCLUSIONS: Less than 5% of the radiomic characteristics identified tumor regions of medical-clinical interest in T1 and T2 sequences of conventional magnetic resonance imaging. The first-order and second-order radiomic features suggest support to investigators and clinicians for careful evaluation for diagnosis, patient classification, and multimodality cancer treatment planning.

The genetic history of the Southern Andes from present-day Mapuche ancestry.

The southernmost regions of South America harbor some of the earliest evidence of human presence in the Americas. However, connections with the rest of the continent and the contextualization of present-day indigenous ancestries remain poorly resolved. In this study, we analyze the genetic ancestry of one of the largest indigenous groups in South America: the Mapuche. We generate genome-wide data from 64 participants from three Mapuche populations in Southern Chile: Pehuenche, Lafkenche, and Huilliche. Broadly, we describe three main ancestry blocks with a common origin, which characterize the Southern Cone, the Central Andes, and Amazonia. Within the Southern Cone, ancestors of the Mapuche lineages differentiated from those of the Far South during the Middle Holocene and did not experience further migration waves from the north. We find that the deep genetic split between the Central and Southern Andes is followed by instances of gene flow, which may have accompanied the southward spread of cultural traits from the Central Andes, including crops and loanwords from Quechua into Mapudungun (the language of the Mapuche). Finally, we report close genetic relatedness between the three populations analyzed, with the Huilliche characterized additionally by intense recent exchanges with the Far South. Our findings add new perspectives on the genetic (pre)history of South America, from the first settlement through to the present-day indigenous presence. Follow-up fieldwork took these results back to the indigenous communities to contextualize the genetic narrative alongside indigenous knowledge and perspectives. VIDEO ABSTRACT.

Diaphragmatic Ultrasound Predictors of High-Flow Nasal Cannula Therapeutic Failure in Critically Ill Patients With SARS-CoV-2 Pneumonia.

OBJECTIVES: High flow nasal cannula (HFNC) is frequently used in patients with acute respiratory failure, but there is limited evidence regarding predictors of therapeutic failure. The objective of this study was to assess diaphragmatic ultrasound criteria as predictors of failure to HFNC, defined as the need for orotracheal intubation or death. METHODS: Prospective cohort study including adult patients consecutively admitted to the critical care unit, from July 24 to October 20, 2020, with respiratory failure secondary to SARS-CoV-2 pneumonia who required HFNC. After 12 hours of HFNC initiation we measured ROX index (ratio of SpO2 /FiO2 to respiratory rate), excursion and diaphragmatic contraction speed (diaphragmatic excursion/inspiratory time) by ultrasound, both in supine and prone position. RESULTS: In total, 41 patients were analyzed, 25 succeeded and 16 failed HFNC therapy. At 12 hours, patients who succeeded HFNC therapy presented higher ROX index in supine position (9.8 [9.1-15.6] versus 5.4 [3.9-6.8], P < .01), and higher PaO2 /FiO2 ratio (186 [135-236] versus 117 [103-162] mmHg, P = .03). To predict therapeutic failure, the supine diaphragmatic contraction speed presented sensitivity of 89% and a specificity of 57%, while the ROX index presented a sensitivity of 92.8% and a specificity of 75%. CONCLUSIONS: Diaphragmatic contraction speed by ultrasound emerges as a diagnostic complement to clinical tools to predict HFNC success. Future studies should confirm these results.

Correlation of Biomarkers of Endothelial Injury and Inflammation to Outcome in Hospitalized COVID-19 Patients.

COVID-19 can trigger an intense systemic inflammation and prothrombotic state, leading to a rapid and disproportionate deterioration of lung function. An effective screening tool is essential to identify the patients at risk for severe disease. This observational study was conducted on hospitalized patients with moderate and severe COVID-19 pneumonia in a general hospital in Mexico City between 1 March 2021 and 15 March 2021. Serum samples were analyzed to explore the role of biomarkers of inflammation, coagulation, oxidative stress, and endothelial damage with the severity of the disease. Our results demonstrated that Syndecan-1 and nitrites/nitrates showed a high correlation in severely ill patients. In conclusion, COVID-19 patients with elevated levels of SDC-1 were associated with severe disease. This molecule can potentially be used as a marker for the progression or severity of COVID-19. Preservation of glycocalyx integrity may be a potential treatment for COVID-19.

IL-36γ is secreted through an unconventional pathway using the Gasdermin D and P2X7R membrane pores.

Mucosal innate immunity functions as the first line of defense against invading pathogens. Members of the IL-1 family are key cytokines upregulated in the inflamed mucosa. Inflammatory cytokines are regulated by limiting their function and availability through their activation and secretion mechanisms. IL-1 cytokines secretion is affected by the lack of a signal peptide on their sequence, which prevents them from accessing the conventional protein secretion pathway; thus, they use unconventional protein secretion pathways. Here we show in mouse macrophages that LPS/ATP stimulation induces cytokine relocalization to the plasma membrane, and conventional secretion blockade using monensin or Brefeldin A triggers no IL-36γ accumulation within the cell. In silico modeling indicates IL-36γ can pass through both the P2X7R and Gasdermin D pores, and both IL-36γ, P2X7R and Gasdermin D mRNA are upregulated in inflammation; further, experimental blockade of these receptors' limits IL-36γ release. Our results demonstrate that IL-36γ is secreted mainly by an unconventional pathway through membrane pores formed by P2X7R and Gasdermin D.

Sensitivity and Specificity of Patient-Reported Clinical Manifestations to Diagnose COVID-19 in Adults from a National Database in Chile: A Cross-Sectional Study.

(1) Background: The diagnosis of COVID-19 is frequently made on the basis of a suggestive clinical history and the detection of SARS-CoV-2 RNA in respiratory secretions. However, the diagnostic accuracy of clinical features is unknown. (2) Objective: To assess the diagnostic accuracy of patient-reported clinical manifestations to identify cases of COVID-19. (3) Methodology: Cross-sectional study using data from a national registry in Chile. Infection by SARS-CoV-2 was confirmed using RT-PCR in all cases. Anonymised information regarding demographic characteristics and clinical features were assessed using sensitivity, specificity, and diagnostic odds ratios. A multivariable logistic regression model was constructed to combine epidemiological risk factors and clinical features. (4) Results: A total of 2,187,962 observations were available for analyses. Male participants had a mean age of 43.1 ± 17.5 years. The most common complaints within the study were headache (39%), myalgia (32.7%), cough (31.6%), and sore throat (25.7%). The most sensitive features of disease were headache, myalgia, and cough, and the most specific were anosmia and dysgeusia/ageusia. A multivariable model showed a fair diagnostic accuracy, with a ROC AUC of 0.744 (95% CI 0.743-0.746). (5) Discussion: No single clinical feature was able to fully confirm or exclude an infection by SARS-CoV-2. The combination of several demographic and clinical factors had a fair diagnostic accuracy in identifying patients with the disease. This model can help clinicians tailor the probability of COVID-19 and select diagnostic tests appropriate to their setting.

Arsenic concentration in topsoil of central Chile is associated with aberrant methylation of P53 gene in human blood cells: a cross-sectional study.

Gene expression can be modified in people who are chronically exposed to high concentrations of heavy metals. The soil surrounding the Ventanas Industrial Complex, located on the coastal zone of Puchuncaví and Quintero townships (Chile), contain heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed international standards. The aim of this study was to determine the potential association of the heavy metals in soils, especially arsenic, with the status of methylation of four tumor suppressor genes in permanent residents in those townships. To study the methylation status in genes p53, p16, APC, and RASSF1A, we took blood samples from adults living in areas near the industrial complex for at least 5 years and compared it to blood samples from adults living in areas with normal heavy metal concentrations of soils. Results indicated that inhabitants of an area with high levels of heavy metals in soil have a significantly higher proportion of methylation in the promoter region of the p53 tumor suppressor gene compared with control areas (p-value: 0.0035). This is the first study to consider associations between heavy metal exposure in humans and aberrant DNA methylation in Chile. Our results suggest more research to support consistent decision-making on processes of environmental remediation or prevention of exposure.

Improvement in Quality of Life with Use of Ambient-Assisted Living: Clinical Trial with Older Persons in the Chilean Population.

In Chile, 18% of the population is over 60 years old and is projected to reach 31% in three decades. An aging population demands the development of strategies to improve quality of life (QoL). In this randomized trial, we present the implementation and evaluation of the Quida platform, which consists of a network of unintrusive sensors installed in the houses of elderly participants to monitor their activities and provide assistance. Sixty-nine elderly participants were included. A significant increase in overall QoL was observed amongst participants allocated to the interventional arm (p < 0.02). While some studies point out difficulties monitoring users at home, Quida demonstrates that it is possible to detect presence and movement to identify patterns of behavior in the sample studied, allowing us to visualize the behavior of older adults at different time intervals to support their medical evaluation.

Cambios en la vía aérea después de cirugía ortognática bimaxilar / Airway change after bimaxillary orthognathic surgery

RESUMEN: La cirugía ortognática se realiza en sujetos con algún tipo de alteración esqueletal. Los movimientos maxilo mandibulares tienen impacto en la vía aérea (VA) y este aspecto se debe incorporar en la planificación quirúrgica. El objetivo de esta investigación fue determinar los cambios generados en la VA después de realizada la cirugía ortognática. Se realizó un estudio piloto incluyendo 51 sujetos con deformidad facial de clase II y clase III; se incluyeron en base al estudio del ángulo ANB y el tipo de oclusión dentaria. Se realizaron estudios con tomografía de haz cónico identificando el volumen máximo en la vía área y las áreas mínimas y máximas; además se incluyó la posición del hueso hioide y la inclinación del plano mandibular para relacionar con la morfología de la VA; para definir significancia estadística se estableció un valor de p<0,05 incluyendo las pruebas T de student y T test. Los resultados indicaron que los sujetos clase II aumentaron significativamente el volumen y áreas máximas y mínimas de la VA; los sujetos de clase III esqueletal no presentaron diferencias significativas entre la etapa pre y post quirúrgica; el hueso hioides se presentó significativamente más anterior en ambos en casos de clase II y clase III. Es posible concluir que la VA mejora sustancialmente en sujetos con clase esqueletal facial tipo II y que se mantiene sin cambios en sujetos con clase facial tipo III.

SUMMARY: Orthognathic surgery is performed in subjects with some type of skeletal alteration. Maxillomandibular movements have an impact on the airway (AW) and this aspect must be included into surgical planning. The aim of this research is to determine the changes in the AW after orthognathic surgery. A pilot study was conducted including 51 subjects with class II and class III facial deformity; they were included using the ANB angle and the type of dental occlusion. Cone beam computed tomography were performed showing the maximum volume in the airway and the minimum and maximum areas; in addition, the position of the hyoid bone and the angle of the mandibular plane were included to relate it to the morphology of the AW; to define statistical significance, a value of p<0.05 was established, including the student's t-test and the t-test. The results showed that class II subjects significantly increased the volume and maximum and minimum areas of the AW; skeletal class III subjects did not presented significant differences between the pre- and post-surgical stage; the hyoid bone was in an anterior position in both class II and class III cases. It is possible to conclude that AW improves substantially in subjects with facial class II and remains unchanged in subjects with facial class III.

Relación neutrófilo a linfocito, recuento linfocitario e índices de actividad inflamatoria como factores pronóstico en infecciones por SARS-CoV-2: Un estudio de cohorte prospectiva / Neutrophil to lymphocite ratio and inflammatory biomarkers as prognostic factors amongst patients with COVID-19: A prospective cohort study

INTRODUCTION: Patients with COVID-19 can develop respiratory failure requiring treatment with invasive mechanical ventilation (IMV) and death. It is important to have clinical predictors of these outcomes. OBJECTIVES: To establish the diagnostic accuracy of neutrophil to lymphocyte ratios (NLr) in predicting the need of IMV and survival amongst patients with COVID-19 and to compare this accuracy with other laboratory tests. METHODOLOGY: Prospective cohort study of hospitalized patients with a SArS-CoV-2 infection confirmed by rT-PCr. Clinical, demographic and laboratory predictors were assessed, including LDH, C-reactive protein, absolute lymphocyte counts, serum ferritin and NLr. Statistical analyses were undertaken using receiver-operator characteristics (ROC) curves, which were in turn compared using the method described by Hanley and McNeal. RESULTS: One hundred and twelve patients were studied, most were male (60.7%) with a mean age of 63.4 ± 18.3 years. Twenty-two patients required IMV during their stay and 28 died. The NLr showed a good diagnostic accuracy in detecting patients that would require IMV (AUC 0.70, 95% CI 0.57-0.86) or died during the hospitalization (AUC 0.83, 95%CI 0.75-0.91). A cutoff point of 5.5 or higher had an 80.8% sensitivity and 73.1% specificity in detecting patients that died during their stay. CONCLUSIONS. NLR showed favorable diagnostic properties in detecting patients with COVID-19 at risk of adverse outcomes. Its wide availability and low cost are desirable features that might facilitate its implementation in routine clinical practice.

INTRODUCCIÓN: La infección a SArS-CoV-2 puede generar insuficiencia respiratoria con requerimientos de ventilación mecánica invasiva (VMI). Contar con predictores de este evento es fundamental. OBJETIVOS: Determinar la capacidad diagnóstica de la relación neutrófilo a linfocito (RNL) para predecir necesidad de VMI o muerte y compararla con otros índices de laboratorio. MÉTODOS: Cohorte prospectiva de pacientes hospitalizados con diagnóstico confirmado de COVID-19 por PCr. Se evaluaron predictores clínicos, demográficos y de laboratorio, incluyendo LDH, proteína C reactiva, recuento linfocitario, ferritina y la RNL. Los pacientes fueron seguidos hasta el alta hospitalaria. El análisis estadístico se realizó mediante curvas de características de receptor-operador (rOC) que se compararon mediante el método de Hanley y McNeal. RESULTADOS: Se estudiaron 112 pacientes, 60,7% hombres con media de edad de 63,4 ± 18,3 años. Veintidos ingresaron a ventilación invasiva y 28 fallecieron. La RNL mostró una buena capacidad diagnóstica para detectar pacientes que necesitaron VMI (AUC: 0,70, IC95% 0,57-0,86) o fallecieron durante la hospitalización (AUC: 0,83, IC95% 0,75-0,91). Un punto de corte de 5,5 o superior tuvo una sensibilidad del 80,8% y especificidad del 73,1% para detectar pacientes en riesgo de fallecer por la enfermedad. CONCLUSIONES: La RNL tiene favorables aptitudes diagnósticas en establecer el riesgo de evolución tórpida en casos de infecciones a SArS-CoV-2. La amplia disponibilidad de la prueba y su bajo costo representan características atractivas para su uso en clínica.

Late correction of orbital deformities using customized 3D implant / Corrección tardía de deformidades de órbita usando implantes personalizados 3D

SUMMARY: Late orbital reconstruction is a complex and challenge for surgeons. The aim of this article is to present complex orbital reconstruction using patient specific implant (PSI) strategy and polyetheretherketone (PEEK). A literature review and a cases series of sequelae after complex orbital trauma are presented; cases with great middle third deformities showing defect in the maxilla, nasal area, body of the zygoma and zygomatic arch were included; in both cases the sequelae was for more than 10 years. Virtual planning and PEEK implants were manufacture using a puzzle (two or three parts) by 3D print or injection. Patients were treated and their surgeries carried out without complications, using a minimal surgical approach. No infections were observed, and after 12 months follow-up they were stable showing normal function. PSI based-PEEK for orbital reconstruction are safe, efficient, effective and to obtain orbital morphology with low complications.

RESUMEN: La reconstrucción tardía de la órbita es un desafío complejo para cirujanos. El objetivo de este artículo fue presentar la reconstrucción orbitaria compleja utilizando implante paciente específico (PSI) y polietereterketona (PEEK). Son presentados una revisión de literatura y una serie de casos con secuelas posteriores a un trauma orbitario complejo; además, son presentados casos con gran deformidad del tercio medio del rostro mostrando defectos en maxila, área nasal, cuerpo del hueso cigomático y arco cigomático; ambos casos de secuela fueron por más de 10 años. Planificación virtual e implantes en PEEK fueron creados usando una estrategia de puzzle (dos o tres partes) por inyección o impresión 3D. Los pacientes fueron tratados y sus cirugías realizadas sin complicaciones usando accesos quirúrgicos reducidos. No se observaron infecciones y después de 12 meses de seguimiento permanecieron estables mostrando función normal. Los PSI para reconstrucción orbitaria son seguros, eficientes, efectivos y recuperan morfología de órbita con bajas complicaciones.

Comparative Efficacy of a High-Dose vs Standard-Dose Hepatitis B Revaccination Schedule Among Patients With HIV: A Randomized Clinical Trial.

Importance: Active immunization for hepatitis B virus (HBV) infection is recommended in patients living with HIV. Limited evidence is available about the most appropriate regimen of HBV vaccination among those who have not responded to an initial schedule. Objective: To determine the efficacy of a high-dose schedule compared with a standard dose of HBV vaccination. Design, Setting, and Participants: This double-masked, parallel-group, randomized controlled trial included patients living with HIV at a single outpatient HIV and hepatology clinic in Chile for whom previous HBV vaccination had failed. Patients with hepatitis B surface antibody (anti-HBs) titers less than 10 IU/L after an initial HBV vaccination regimen were included. Consecutive patients were recruited between December 2013 and March 2018. Data were analyzed in June 2018 using intention-to-treat analysis. Intervention: The high-dose HBV vaccination group consisted of 3 doses of 40 µg recombinant hepatitis B vaccine at 0, 1, and 2 months. The standard-dose group received 3 doses 20 µg each at 0, 1, and 2 months. Main Outcomes and Measures: Primary outcome was the serologic response to HBV vaccination (anti-HBs greater than 10 IU/L) 4 to 8 weeks after completion of the schedule. Secondary outcomes were anti-HBs greater than 100 IU/L and seroprotective anti-HBs at 1 year follow up. Results: A total of 107 patients underwent randomization (55 to the standard-dose group, 52 to the high-dose group); 81 (75.7%) were men, and the mean (SD) patient age was 47.0 (13.3) years. Nearly all patients were receiving antiretroviral therapy (105 patients [98%]) and 92 patients (86%) had an undetectable HIV viral load. Mean (SD) CD4 count was 418 (205) cells/mm3. There were no differences in baseline characteristics between groups. Serological response in the high-dose group was found in 36 of 50 patients (72%; 95% CI, 56.9%-82.9%) compared with 28 of 55 patients in the standard-dose group (51%; 95% CI, 37.1%-64.6%) (odds ratio, 2.48; 95% CI, 1.02-6.10; P = .03). Mean (SD) anti-HB levels were 398.0 (433.4) IU/L in the high-dose group and 158.5 (301.4) IU/L in the standard-dose group (P < .001). Of patients with a serological response in the high-dose group, 29 of 36 (80.6%) had anti-HBs titers greater than 100 IU/L compared with 14 of 28 responders (50.0%) in the standard-dose group (P = .02). At 1-year follow-up, 20 of 25 patients (80.0%) with a serological response in the high-dose group had protective anti-HBs vs 9 of 23 patients (39.1%) in the standard-dose group (P = .01). Conclusions and Relevance: The results of this randomized clinical trial suggest that use of a high-dose regimen for HBV revaccination for patients with HIV achieves a higher and longer-lasting serological response as compared with a standard-dose regimen. Trial Registration: ClinicalTrials.gov Identifier: NCT02003703.

Rictor/Mammalian Target of Rapamycin Complex 2 Signaling Protects Colonocytes from Apoptosis and Prevents Epithelial Barrier Breakdown.

Epithelial barrier impairment is a hallmark of several pathologic processes in the gut, including inflammatory bowel diseases. Several intracellular signals prevent apoptosis in intestinal epithelial cells. Herein, we show that in colonocytes, rictor/mammalian target of rapamycin complex 2 (mTORC2) signaling is a prosurvival stimulus. Mechanistically, mTORC2 activates Akt, which, in turn, inhibits apoptosis by phosphorylating B-cell lymphoma 2 (BCL2) associated agonist of cell death (Bad) and preventing caspase-3 activation. Nevertheless, during inflammation, rictor/mTORC2 signaling declines and Akt activity is reduced. Consequently, active caspase-3 increases in surface colonocytes undergoing apoptosis/anoikis and causes epithelial barrier breakdown. Likewise, Rictor ablation in intestinal epithelial cells interrupts mTORC2/Akt signaling and increases apoptosis/anoikis of surface colonocytes without affecting the crypt architecture. The increase in epithelial permeability induced by Rictor ablation produces a mild inflammatory response in the colonic mucosa, but minimally affects the development/establishment of colitis. The data identify a previously unknown mechanism by which rictor/mTORC2 signaling regulates apoptosis/anoikis in intestinal epithelial cells during colitis and clarify its role in the maintenance of the intestinal epithelial barrier.