Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation.

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Native Entomopathogenic Fungi Isolated from Rhynchophorus palmarum (Linnaeus, 1758) in Northeast Brazil.

Both palm weevils, the South American (Rhynchophorus palmarum) (SAPW) and the red palm weevil (R. ferrugineus, RPW), are present in South America, affecting commercial, ornamental, and native palms. These pests oviposit and thrive on selected Arecaceae. R. palmarum mainly infests coconut (Cocos nucifera), oil palms (Elaeis guineensis), and other ornamental and native palms in America, causing a significant social impact on growers. The weevils fulfill a significant ectosymbiotic macro- and microorganism role in the first period of larval development, worsening the damage which, during this period, is not yet apparent. Palm protection in the Brazilian context suggests the use of indigenous agents for microbiological biocontrol. This research identifies three Brazilian Beauveria bassiana isolates: CVAD01, CVAD02, and CVAD06. The results suggest that the strain's impact on R. palmarum can also be compared with that of the commercial strain Beauveria bassiana. Phylogenetic analysis allowed the delimitation of species of Beauveria (Hypocreales). Pathogenicity tests caused significant mortality in R. palmarum. The isolates CVAD01, CVAD02, and CVADO6 showed high pathogenicity between 7 and 21 days, with mortality rates between 90 and 100%, suggesting that they may be effective biological control agents of R. palmarum in the field when used, within available means, to mitigate the impact of R. palmarum and R. ferrugineus in South America.

Caveolin-1-dependent tenascin C inclusion in extracellular vesicles is required to promote breast cancer cell malignancy.

Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer.

Caveolin-1 (CAV1) is a protein that in breast cancer increases with disease progression. Extracellular vesicles (EVs) from breast cancer cells with CAV1 also contain Tenascin C (TNC) protein, but the importance of TNC remained to be defined. EVs were identified by size, microscopy and protein analysis. The effects of EVs on breast cancer cells were studied using cells and experiments in animals. CAV1 expression promotes TNC inclusion into EVs, which increased the aggressiveness of recipient breast cancer cells. In animals, only EVs with TNC increased features associated with cancer spread, while EVs lacking TNC reduced tumor growth.

An advanced biphasic porous and injectable scaffold displays a fine balance between mechanical strength and remodeling capabilities essential for cartilage regeneration.

An important challenge in tissue engineering is the regeneration of functional articular cartilage (AC). In the field, biomimetic hydrogels are being extensively studied as scaffolds that recapitulate microenvironmental features or as mechanical supports for transplanted cells. New advanced hydrogel formulations based on salmon methacrylate gelatin (sGelMA), a cold-adapted biomaterial, are presented in this work. The psychrophilic nature of this biomaterial provides rheological advantages allowing the fabrication of scaffolds with high concentrations of the biopolymer and high mechanical strength, suitable for formulating injectable hydrogels with high mechanical strength for cartilage regeneration. However, highly intricate cell-laden scaffolds derived from highly concentrated sGelMA solutions could be deleterious for cells and scaffold remodeling. On this account, the current study proposes the use of sGelMA supplemented with a mesophilic sacrificial porogenic component. The cytocompatibility of different sGelMA-based formulations is tested through the encapsulation of osteoarthritic chondrocytes (OACs) and stimulated to synthesize extracellular matrix (ECM) components in vitro and in vivo. The sGelMA-derived scaffolds reach high levels of stiffness, and the inclusion of porogens impacts positively the scaffold degradability and molecular diffusion, improved fitness of OACs, increased the expression of cartilage-related genes, increased glycosaminoglycan (GAG) synthesis, and improved remodeling toward cartilage-like tissues. Altogether, these data support the use of sGelMA solutions in combination with mammalian solid gelatin beads for highly injectable formulations for cartilage regeneration, strengthening the importance of the balance between mechanical properties and remodeling capabilities.

Ocular Manifestations of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic disease connected to the immune system, with a predilection for the gastrointestinal tract. However, a large proportion of the patients have extraintestinal manifestations (EIM), and the ocular system is affected in some patients. The clinical presentation of ocular pathology is broad, ranging from asymptomatic cases to blindness, leading to high morbidity. Ocular complications can be primary and, in general, are associated with episodes of acute flare-ups that subside with immunological management of the digestive disease. Secondary complications arise from the primary ones and as adverse effects of immunological treatment. In addition, on many occasions, the ocular manifestation may appear prior to the presentation of digestive symptoms. The presence of a multidisciplinary team that includes a gastroenterologist and an ophthalmologist is important in order to achieve early diagnosis of ocular complications, thereby preventing, treating, and avoiding unfavorable and irreversible long-term ocular sequelae.

A novel porous hydrogel based on hybrid gelation for injectable and tough scaffold implantation and tissue engineering applications.

Although there have been many advances in injectable hydrogels as scaffolds for tissue engineering or as payload-containing vehicles, the lack of adequate microporosity for the desired cell behavior, tissue integration, and successful tissue generation remains an important drawback. Herein, we describe an effective porous injectable system that allowsin vivoformation of pores through conventional syringe injection at room temperature. This system is based on the differential melting profiles of photocrosslinkable salmon gelatin and physically crosslinked porogens of porcine gelatin (PG), in which PG porogens are solid beads, while salmon methacrylamide gelatin remains liquid during the injection procedure. After injection and photocrosslinking, the porogens were degraded in response to the physiological temperature, enabling the generation of a homogeneous porous structure within the hydrogel. The resultant porogen-containing formulations exhibited controlled gelation kinetics within a broad temperature window (18.5 ± 0.5-28.8 ± 0.8 °C), low viscosity (133 ± 1.4-188 ± 16 cP), low force requirements for injectability (17 ± 0.3-39 ± 1 N), robust mechanical properties after photo-crosslinking (100.9 ± 3.4-332 ± 13.2 kPa), and favorable cytocompatibility (>70% cell viability). Remarkably,in vivosubcutaneous injection demonstrated the suitability of the system with appropriate viscosity and swift crosslinking to generate porous hydrogels. The resulting injected porous constructs showed favorable biocompatibility and facilitated cell infiltration for desirable potential tissue remodeling. Finally, the porogen-containing formulations exhibited favorable handling, easy deposition, and good shape fidelity when used as bioinks in 3D bioprinting technology. This injectable porous system serves as a platform for various biomedical applications, thereby inspiring future advances in cell therapy and tissue engineering.

Understanding the Molecular Conformation and Viscoelasticity of Low Sol-Gel Transition Temperature Gelatin Methacryloyl Suspensions.

For biomedical applications, gelatin is usually modified with methacryloyl groups to obtain gelatin methacryloyl (GelMA), which can be crosslinked by a radical reaction induced by low wavelength light to form mechanically stable hydrogels. The potential of GelMA hydrogels for tissue engineering has been well established, however, one of the main disadvantages of mammalian-origin gelatins is that their sol-gel transitions are close to room temperature, resulting in significant variations in viscosity that can be a problem for biofabrication applications. For these applications, cold-water fish-derived gelatins, such as salmon gelatin, are a good alternative due to their lower viscosity, viscoelastic and mechanical properties, as well as lower sol-gel transition temperatures, when compared with mammalian gelatins. However, information regarding GelMA (with special focus on salmon GelMA as a model for cold-water species) molecular conformation and the effect of pH prior to crosslinking, which is key for fabrication purposes since it will determine final hydrogel's structure, remains scarce. The aim of this work is to characterize salmon gelatin (SGel) and salmon methacryloyl gelatin (SGelMA) molecular configuration at two different acidic pHs (3.6 and 4.8) and to compare them to commercial porcine gelatin (PGel) and methacryloyl porcine gelatin (PGelMA), usually used for biomedical applications. Specifically, we evaluated gelatin and GelMA samples' molecular weight, isoelectric point (IEP), their molecular configuration by circular dichroism (CD), and determined their rheological and thermophysical properties. Results showed that functionalization affected gelatin molecular weight and IEP. Additionally, functionalization and pH affected gelatin molecular structure and rheological and thermal properties. Interestingly, the SGel and SGelMA molecular structure was more sensitive to pH changes, showing differences in gelation temperatures and triple helix formation than PGelMA. This work suggests that SGelMA presents high tunability as a biomaterial for biofabrication, highlighting the importance of a proper GelMA molecular configuration characterization prior to hydrogel fabrication.

Three double-dose reinforced hepatitis B revaccination scheme for patients with cirrhosis unresponsive to the standard regimen: an open-label randomised clinical trial.

OBJECTIVE: We aimed to compare the response rates between two different hepatitis B virus vaccination schedules for cirrhotic subjects who were non-responders to the first three 40 µg doses (month 0-1-2), and identify factors associated with the final response. DESIGN: A total of 120 cirrhotic patients (72.5% decompensated) were randomised at a 1:1 ratio to receive a single 40 µg booster vaccination at month 6 (classical arm) versus an additional round of three new 40 µg doses administered at monthly intervals (experimental arm). The main outcome was the rate of postvaccinal anti-hepatitis B surface antibodies levels ≥10 mIU/mL. RESULTS: Efficacy by ITT analysis was higher in the experimental arm (46.7%) than in the classical one (25%); OR 2.63, p=0.013. The experimental arm increased response rates compared with the classical one from 31% to 68% (OR 4.72; p=0.007), from 24.4% to 50% (OR 3.09; p=0.012) and from 24.4% to 53.8% (OR 3.62; p=0.007), in Child A, Model for End-Stage Liver Disease (MELD) <15 and MELD-Na<15 patients, respectively. Patients with more advanced liver disease did not benefit from the reinforced scheme. Both regimens showed similar safety profiles. Multivariable analysis showed that the experimental treatment was independently response associated when adjusted across three logistic regression models indicating equivalent cirrhosis severity. CONCLUSION: For cirrhotic patients, the revaccination of non-responders to the first three dose cycle, with three additional 40 µg doses, achieved significantly better response rates to those obtained with an isolated 40 µg booster dose. TRIAL REGISTRATION NUMBER: NCT01884415.

KRAS Gene Mutation in Patients Undergoing Liver Resections for Colorectal Cancer. Is There an Advantage to Anatomical Resections?

Introduction: Several factors have been described to make a prognostic assessment of patients with liver metastases due to colorectal cancer and to define the benefit of the surgical management of metastatic involvement; one of these factors is the status of the KRAS gene since its mutation is associated with worse outcomes. This study aims to describe the outcomes for a retrospective series of patients after liver resections for metastatic colorectal cancer concerning KRAS gene status. Materials and methods: The study involves a retrospective cohort of patients undergoing liver metastasectomy for colorectal cancer with KRAS mutation study from 2009-2013 at the National Institute of Cancerology in Colombia. Five-year survival analyses (overall and disease-free) were performed according to KRAS mutation status and the type of liver resection performed using the Kaplan-Meier estimate. Results: 35 patients undergoing liver metastasectomy were analyzed, of which 42.8% had KRAS gene mutation. Median overall survival was 34.2 months for patients with KRAS- mutant and 46.5 for non-mutant. The median survival for KRAS-mutant patients with anatomic resections was 43.5 months versus 23.5 months for nonanatomic resections. Conclusions: Performing anatomic resections during liver metastasectomy in patients with KRAS mutants could be associated with an improvement in overall survival. It is necessary to continue building the evidence for adequate decision-making in patients with KRAS mutants who will undergo liver resections.

Introducción: se han descrito varios factores para realizar una evaluación pronóstica de los pacientes con metástasis hepáticas por cáncer colorrectal y definir el beneficio en el manejo quirúrgico del compromiso metastásico; uno de estos factores es el estado del gen KRAS, debido a que su mutación está relacionada con peores desenlaces. El objetivo de este estudio es describir los desenlaces para una serie retrospectiva de pacientes después de resecciones hepáticas por metástasis de cáncer colorrectal en relación con el estado del gen KRAS. Metodología: cohorte retrospectiva de pacientes llevados a metastasectomía hepática por cáncer colorrectal con estudio de mutación KRAS durante el período 2009-2013, en el Instituto Nacional de Cancerología en Colombia. Se realizaron análisis de supervivencia a 5 años (global y libre de enfermedad) según el estado de mutación KRAS y según el tipo de resección hepática realizada mediante el método de Kaplan-Meier. Resultados: se analizaron a 35 pacientes llevados a metastasectomía hepática, de los cuales el 42,8% presentaba mutación del gen KRAS. La supervivencia global media fue de 34,2 meses para los pacientes con KRAS mutado y de 46,5 para los no mutados. La supervivencia media para los pacientes con KRAS mutado con resecciones anatómicas fue de 43,5 meses frente a 23,5 meses en los que se realizaron resecciones no anatómicas. Conclusiones: realizar resecciones anatómicas durante la metastasectomía hepática en los pacientes con KRAS mutado podría estar asociado con una mejoría en la supervivencia global. Se requiere continuar en la construcción de la evidencia que permita una adecuada toma de decisiones de los pacientes con KRAS mutado que serán llevados a resecciones hepáticas.

"Ectomosphere": Insects and Microorganism Interactions.

This study focuses on interacting with insects and their ectosymbiont (lato sensu) microorganisms for environmentally safe plant production and protection. Some cases help compare ectosymbiont microorganisms that are insect-borne, -driven, or -spread relevant to endosymbionts' behaviour. Ectosymbiotic bacteria can interact with insects by allowing them to improve the value of their pabula. In addition, some bacteria are essential for creating ecological niches that can host the development of pests. Insect-borne plant pathogens include bacteria, viruses, and fungi. These pathogens interact with their vectors to enhance reciprocal fitness. Knowing vector-phoront interaction could considerably increase chances for outbreak management, notably when sustained by quarantine vector ectosymbiont pathogens, such as the actual Xylella fastidiosa Mediterranean invasion episode. Insect pathogenic viruses have a close evolutionary relationship with their hosts, also being highly specific and obligate parasites. Sixteen virus families have been reported to infect insects and may be involved in the biological control of specific pests, including some economic weevils. Insects and fungi are among the most widespread organisms in nature and interact with each other, establishing symbiotic relationships ranging from mutualism to antagonism. The associations can influence the extent to which interacting organisms can exert their effects on plants and the proper management practices. Sustainable pest management also relies on entomopathogenic fungi; research on these species starts from their isolation from insect carcasses, followed by identification using conventional light or electron microscopy techniques. Thanks to the development of omics sciences, it is possible to identify entomopathogenic fungi with evolutionary histories that are less-shared with the target insect and can be proposed as pest antagonists. Many interesting omics can help detect the presence of entomopathogens in different natural matrices, such as soil or plants. The same techniques will help localize ectosymbionts, localization of recesses, or specialized morphological adaptation, greatly supporting the robust interpretation of the symbiont role. The manipulation and modulation of ectosymbionts could be a more promising way to counteract pests and borne pathogens, mitigating the impact of formulates and reducing food insecurity due to the lesser impact of direct damage and diseases. The promise has a preventive intent for more manageable and broader implications for pests, comparing what we can obtain using simpler, less-specific techniques and a less comprehensive approach to Integrated Pest Management (IPM).

A Psychrophilic GelMA: Breaking Technical and Immunological Barriers for Multimaterial High-Resolution 3D Bioprinting.

The increasing demand for tissue replacement has encouraged scientists worldwide to focus on developing new biofabrication technologies. Multimaterials/cells printed with stringent resolutions are necessary to address the high complexity of tissues. Advanced inkjet 3D printing can use multimaterials and attain high resolution and complexity of printed structures. However, a decisive yet limiting aspect of translational 3D bioprinting is selecting the befitting material to be used as bioink; there is a complete lack of cytoactive bioinks with adequate rheological, mechanical, and reactive properties. This work strives to achieve the right balance between resolution and cell support through methacrylamide functionalization of a psychrophilic gelatin and new fluorosurfactants used to engineer a photo-cross-linkable and immunoevasive bioink. The syntonized parameters following optimal formulation conditions allow proficient printability in a PolyJet 3D printer comparable in resolution to a commercial synthetic ink (∼150 µm). The bioink formulation achieved the desired viability (∼80%) and proliferation of co-printed cells while demonstrating in vivo immune tolerance of printed structures. The practical usage of existing high-resolution 3D printing systems using a novel bioink is shown here, allowing 3D bioprinted structures with potentially unprecedented complexity.

Laminin as a Biomarker of Blood-Brain Barrier Disruption under Neuroinflammation: A Systematic Review.

Laminin, a non-collagenous glycoprotein present in the brain extracellular matrix, helps to maintain blood-brain barrier (BBB) integrity and regulation. Neuroinflammation can compromise laminin structure and function, increasing BBB permeability. The aim of this paper is to determine if neuroinflammation-induced laminin functional changes may serve as a potential biomarker of alterations in the BBB. The 38 publications included evaluated neuroinflammation, BBB disruption, and laminin, and were assessed for quality and risk of bias (protocol registered in PROSPERO; CRD42020212547). We found that laminin may be a good indicator of BBB overall structural integrity, although changes in expression are dependent on the pathologic or experimental model used. In ischemic stroke, permanent vascular damage correlates with increased laminin expression (ß and γ subunits), while transient damage correlates with reduced laminin expression (α subunits). Laminin was reduced in traumatic brain injury and cerebral hemorrhage studies but increased in multiple sclerosis and status epilepticus studies. Despite these observations, there is limited knowledge about the role played by different subunits or isoforms (such as 411 or 511) of laminin in maintaining structural architecture of the BBB under neuroinflammation. Further studies may clarify this aspect and the possibility of using laminin as a biomarker in different pathologies, which have alterations in BBB function in common.

Perfil demográfico y clínico de la poliarteritis nodosa sistémica y cutánea en un grupo de pacientes pediátricos de Medellín, 2010-2019 / Demographic and clinical profile of systemic and cutaneous Polyarteritis nodosa in a group of pediatric patients in Medellin, 2010-2019

Resumen Objetivo: describir las principales características demográficas y clínicas de los pacientes pediátricos con poliarteritis nodosa (PAN). Metodología: estudio descriptivo retrospectivo. Resultados: se obtuvieron las historias clínicas de menores de 18 años con diagnóstico de vasculitis o PAN atendidos entre el 2010 y 2019 en dos hospitales de Medellín. Se incluyeron 19 pacientes, 11 clasificados como PAN cutánea (PANC) según la definición de la Liga Europea contra el Reumatismo y la Sociedad Europea de Reumatología Pediátrica, y 8 como PAN sistémica (PANS) acorde con los criterios de Ankara 2008. El 57,9 % fueron varones (n = 11). La mediana de la edad en el diagnóstico fue 10 años (3-17 años) y del tiempo de seguimiento: 15 meses (0-105 meses). Las manifestaciones más frecuentes fueron nódulos subcutáneos (84,2 %), fiebre (57,9 %), artralgias (57,9 %) y dolor en las pantorrillas (52,6 %). Los pacientes con PANS presentaron más pérdida de peso y hemoglobina baja. 5 niños cursaron con úlceras (26,3 %) cuatro con PANC; 2 exhibieron necrosis lingual (10,5 %) y 2 necrosis digital (10,5 %), todos con PANC. El promedio de la PCR fue de 10,2 mg/dl (0,33-45,3) y, de la eritrosedimentación: 74 mm/hora (15-127 mm/hora). En las imágenes hubo un realce meníngeo, aneurismas intrahepáticas y mesentéricos, entre otros hallazgos. Todos recibieron esteroides sistémicos. Ninguno falleció. Conclusión: en esta serie, la PAN pediátrica fue más común en niños de edad escolar. La PANC fue más frecuente que la PANS. Las manifestaciones más descritas fueron los nódulos subcutáneos, las mialgias, la fiebre, las artralgias y el dolor en las pantorrillas. Aunque se ha considerado la PANC como una enfermedad benigna, estos pacientes pueden requerir tratamiento con glucocorticoides e inmunosupresores.

Summary Objective: To describe the main demographic and clinical characteristics of patients who were diagnosed with childhood polyarteritis nodosa (PAN). Methods: A descriptive study was conducted using retrospective data Results: The clinical registries from patients under 18th years with vasculitis or PAN diagnosis attended between 2010 and 2019 in two Medical Centers from Medellín were obtained. Nineteen patients were included: eleven classified as cutaneous PAN (PANC) according to the definition of the European League Against Rheumatism and the European Society of Pediatric Rheumatology and eight as systemic PAN according to Ankara 2008 Criteria. 57.9% were male. The median age at diagnosis was ten years (3-17), and the median follow-up period was 15 months (0-105). The most common clinical characteristics were subcutaneous nodules (84.2%), fever (57.9%), arthralgias (57.9%), and calf pain (52.6%). SPAN patients had more frequent weight loss and lower hemoglobin. Five patients had ulcers (26.3%), four of them with CPAN; two patients had lingual necrosis (10.5%), and two digital necrosis (10.5%), all of them also with CPAN. CRP mean was 10.2 mg/dl (0.33-45.3) and mean erythrocyte sedimentation rate (ESR) was 74 mm/h (15-127 mm/h). Meningeal enhancing, intrahepatic, and mesenteric aneurism, among others, were reported in diagnostic images. All patients required treatment with systemic glucocorticoid. None of the patients died during the follow-up period. Conclusions: In this pediatric series from Medellín-Colombia, PAN was more common in boys of school age. CPAN was more frequent than SPAN. The clinical characteristics most reported were subcutaneous nodules, myalgias, arthralgias, and calf pain. Although CPAN has been considered a benign disease, these patients may require systemic glucocorticoid and immunosuppressive therapy.

Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study.

BACKGROUND & AIMS: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. METHODS: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. RESULTS: Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. CONCLUSIONS: This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.

Recommendations for the diagnosis and management of persons with suspected vaccine-induced immune thrombotic thrombocytopenia (VITT) / Recomendaciones para diagnostico y manejo de personas con trombocitopenia trombotica inmune inducida por vacunas (VITT)

Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.

Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo

Isolation of a Novel Alphabaculovirus (Baculoviridae) from Automeris liberia (Cramer, 1780) (Lepidoptera: Saturniidae) in African Oil Palms in Brazil.

A novel baculovirus observed to infect Automeris liberia (Cramer) (bullseye moth) is here described. Caterpillars of A. liberia with symptoms of viral infection were collected from African oil palm plantations in Tailândia, PA, Brazil. Macerated caterpillars were then offered to caterpillars of Automeris cinctistriga (Felder & Rogenhoper), leading to viral symptoms and death before pupation. A transmission electron microscope was used for virus ultrastructural identification. The presence of viral occlusion bodies (OBs) containing multiple nucleocapsids was observed and such features are compatible with Alphabaculovirus (Baculoviridae). Molecular detection by PCR with primers for polyhedrin gene (polh) and for late expression factor-8 gene (lef-8), confirmed that this isolate belonged to Alphabaculovirus genus. To our knowledge, this is the first record of a baculovirus isolated from or associated to Automeris. The name Automeris liberia nucleopolyhedrovirus (AuliNPV) is proposed for the new virus.

Computed tomography (CT) scan identified necrosis, but is it a reliable single parameter for discerning between malignant and benign adrenocortical tumors?

BACKGROUND: Adrenocortical carcinoma is a rare malignant tumor with a poor prognosis. Discernment of adrenocortical carcinoma in an adrenal mass through imaging studies is paramount for early surgical treatment. Recently, necrosis has been proposed as a single morphological parameter for adrenocortical carcinoma diagnosis. The aim of this study was to analyze the measures of diagnostic efficiency of necrosis and the different computed tomography-scan features related to adrenocortical carcinoma diagnosis. METHODS: We conducted a case-control study of patients surgically treated for an adrenal mass with histopathological report consistent with adrenocortical carcinoma (cases) and adrenocortical adenoma (control patients) between 1987 and 2019. Radiological features on computed tomography scan were collected. Bivariate and multivariate statistical analyses were performed for the different imaging features. The measures of diagnostic efficiency for each feature were calculated. Concordance analysis between image-detected and histopathological-identified necrosis was performed. RESULTS: Eighteen adrenocortical carcinoma and 41 adrenocortical adenomas were included. Differences between adrenocortical carcinoma and adrenocortical adenoma were found regarding heterogeneity (odds ratio 4.53, 95% confidence interval 2.3-8.9; P < .0001), tumor size ≥4 cm (odds ratio 3.5, 95% confidence interval 2.05-6.14; P < .0001), and attenuation index ≥10 Hounsfield units (odds ratio 1.9, 95% confidence interval 1.3-2.6; P = .001). Necrosis was the most important imaging feature significantly associated with adrenocortical carcinoma (odds ratio 35, 95% confidence interval 5.1-241.6; P < .0001), present in all adrenocortical carcinoma cases. After measures of diagnostic efficiency calculation, necrosis had the highest diagnostic accuracy (98%). Cohen's kappa for concordance between image-detected and histopathological-identified necrosis was 90.4% (P < .0001). CONCLUSION: Computed tomography scan-detected necrosis is a reliable radiological feature to discern adrenocortical carcinoma from adrenocortical adenomas.