Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance.

The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow1,2 through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.

Circulating myeloid-derived MMP8 in stress susceptibility and depression.

Psychosocial stress has profound effects on the body, including the immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.

Exploring the anatomical factors influencing testes elasticity via ultrasound shear wave elastography: Preliminary results

Purpose: The aim of this study is to evaluate the anatomical factors influencing elasticity values of normal testicular parenchyma using shear wave elastography (SWE). Methods: This study examined 68 healthy male volunteers (117 testes in which standard transverse axis ultrasonography views could be obtained) via conventional scrotal ultrasonography and SWE. Both the mean (EMean) and standard deviation (ESD) elasticity values were acquired. Results: In the standard transverse axis view of the rete testis at the mid-lateral edge of the testes, the EMean values in 2mm the testicular parenchyma from the rete testis and the testicular capsule at the same level as the rete testis were all significantly larger than in the central zone (P<0.001, P<0.001, respectively). The EMean value in the testicular parenchyma 2mm from the testicular capsule on the line formed approximately 45° below the horizontal line of the rete testis was significantly larger than in the rete testis approximately 45° above the horizontal line (P<0.001). In two standard transverse axis views, the ESD values in other regions were significantly larger than those in the central zones (all P<0.001). Also, the EMean values in the transmediastinal arteries were larger than those of the surrounding normal testicular parenchyma (P<0.001). Conclusion: Based on SWE, factors including the testicular capsule, the density of testicular fibrous septa, the depth of the Q-Box™, and the transmediastinal artery may influence the testes elasticity measurement. (AU)

Thymic mimetic cells function beyond self-tolerance.

Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2-7. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations.

Strain-rate-dependent material properties of human lung parenchymal tissue using inverse finite element approach.

Automobile crashes and blunt trauma often lead to life-threatening thoracic injuries, especially to the lung tissues. These injuries can be simulated using finite element-based human body models that need dynamic material properties of lung tissue. The strain-rate-dependent material parameters of human parenchymal tissues were determined in this study using uniaxial quasi-static (1 mm/s) and dynamic (1.6, 3, and 5 m/s) compression tests. A bilinear material model was used to capture the nonlinear behavior of the lung tissue, which was implemented using a user-defined material in LS-DYNA. Inverse mapping using genetic algorithm-based optimization of all experimental data with the corresponding FE models yielded a set of strain-rate-dependent material parameters. The bilinear material parameters are obtained for the strain rates of 0.1, 100, 300, and 500 s-1. The estimated elastic modulus increased from 43 to 153 kPa, while the toe strain reduced from 0.39 to 0.29 when the strain rate was increased from 0.1 to 500 s-1. The optimized bilinear material properties of parenchymal tissue exhibit a piecewise linear relationship with the strain rate.

Longitudinal analysis of bovine mammary gland development.

Many studies on bovine mammary glands focus on one stage of development. Often missing in those studies are repeated measures of development from the same animals. As milk production is directly affected by amount of parenchymal tissue within the udder, understanding mammary gland growth along with visualization of its structures during development is essential. Therefore, analysis of ultrasound and histology data from the same animals would result in better understanding of mammary development over time. Thus, this research aimed to describe mammary gland development using non-invasive and invasive tools to delineate growth rate of glandular tissue responsible for potential future milk production. Mammary gland ultrasound images, biopsy samples, and blood samples were collected from 36 heifer dairy calves beginning at 10 weeks of age, and evaluated at 26, 39, and 52 weeks. Parenchyma was quantified at 10 weeks of age using ultrasound imaging and histological evaluation, and average echogenicity was utilized to quantify parenchyma at later stages of development. A significant negative correlation was detected between average echogenicity of parenchyma at 10 weeks and total adipose as a percent of histological whole tissue at 52 weeks. Additionally, a negative correlation between average daily gain at 10 and 26 weeks and maximum echogenicity at 52 weeks was present. These results suggest average daily gain and mammary gland development prior to 39 weeks of age is associated with development of the mammary gland after 39 weeks. These findings could be predictors of future milk production, however this must be further explored.

Analysis of Morphological and Morphometric Changes in a Parenchymal Tissue after the Radiofrequency Ablation Procedure.

Background and Objectives: Prostate cancer is on the rise in the European Union, and radiofrequency ablation (RFA) is one of the minimally invasive treatment options used for its treatment. Therefore, the aim of this study was to investigate and analyze the effects of RFA on prostate tissues. Materials and Methods: A standard prostate RFA procedure was performed on 13 non-purebred dogs in three sessions: no cooling (NC), cooling with a 0.1% NaCl solution (C.01), and cooling using a 0.9% NaCl solution (C.09). Microtome-cut 2-3 µm sections of prostate samples were stained with hematoxylin and eosin and further examined. Results: A histopathologic evaluation identified four zones of exposure: direct, application, necrosis, and transitional, as the damage on tissues decreased going further from the ablation site. The areas and perimeters of these zones were calculated, and geometric shapes of ablative lesions were evaluated using the quotient formula. Areas and perimeters of prostate tissue lesions in the NC and C.09 sessions were of similar size, whereas those found in C.01 were statistically significantly smaller. Lesions observed in session C.01 were of the most regular geometric shape, while the most irregular ones were found in session C.09. The shapes of lesions closest to the ablation electrode were the most irregular, becoming more regular the further away from the electrode they were. Conclusions: Prostate RFA leads to tissue damage with distinct morphological zones. Notably, the prostate lesions were the smallest and the most regular in shape after RFA procedures using the 0.1% NaCl cooling solution. It can be argued that smaller ablation sites may result in smaller scars, thus allowing for faster tissue healing if the blood flow and innervation at the ablation site are not compromised.

Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts.

BACKGROUND: Gilts experiencing sustained hyperprolactinemia from d 90 to 109 of gestation showed an early onset of lactogenesis coupled with premature mammary involution. To better understand the molecular mechanisms underlying the premature mammary involution observed in these gilts, a transcriptomic analysis was undertaken. Therefore, this study aimed to explore the effect of hyperprolactinemia on the global transcriptome in the mammary tissue of late gestating gilts and identify the molecular pathways involved in triggering premature mammary involution. METHODS: On d 90 of gestation, gilts received daily injections of (1) canola oil until d 109 ± 1 of gestation (CTL, n = 18); (2) domperidone (to induce hyperprolactinemia) until d 96 ± 1 of gestation (T7, n = 17) or; (3) domperidone (until d 109 ± 1 of gestation (T20, n = 17). Mammary tissue was collected on d 110 of gestation and total RNA was isolated from six CTL and six T20 gilts for microarray analysis. The GeneChip® Porcine Gene 1.0 ST Array was used for hybridization. Functional enrichment analyses were performed to explore the biological significance of differentially expressed genes, using the DAVID bioinformatics resource. RESULTS: The expression of 335 genes was up-regulated and that of 505 genes down-regulated in the mammary tissue of T20 vs CTL gilts. Biological process GO terms and KEGG pathways enriched in T20 vs CTL gilts reflected the concurrent premature lactogenesis and mammary involution. When looking at individual genes, it appears that mammary cells from T20 gilts can simultaneously upregulate the transcription of milk proteins such as WAP, CSN1S2 and LALBA, and genes triggering mammary involution such as STAT3, OSMR and IL6R. The down-regulation of PRLR expression and up-regulation of genes known to inactivate the JAK-STAT5 pathway (CISH, PTPN6) suggest the presence of a negative feedback loop trying to counteract the effects of hyperprolactinemia. CONCLUSIONS: Genes and pathways identified in this study suggest that sustained hyperprolactinemia during late-pregnancy, in the absence of suckling piglets, sends conflicting pro-survival and cell death signals to mammary epithelial cells. Reception of these signals results in a mammary gland that can simultaneously synthesize milk proteins and initiate mammary involution.

Protocolo clínico de atendimento de pneumonia adquirida na comunidade para Pronto-Socorro Infantil do Hospital do Servidor Público Municipal de São Paulo / Clinical protocol for community-acquired pneumonia care for the Children's Emergency Room of the Hospital do Servidor Público Municipal de São Paulo

A pneumonia adquirida na comunidade (PAC) é a infecção aguda do parênquima pulmonar que ocorre no meio comunitário. A PAC representa a maior causa de morbidade e mortalidade em todo o mundo em crianças abaixo de cinco anos. Nesta faixa etária, a etiologia viral é a mais comum; porém, dentre as causas bacterianas, o Streptoccocus pneumoniae é o mais prevalente. As manifestações clínicas variam de acordo com o patógeno, hospedeiro e da gravidade da doença, sendo geralmente descrita com tosse, febre e desconforto respiratório. A PAC complicada é a pneumonia que, apesar do uso de antibióticos, evolui com complicações locais ou sistêmicas. Nos pacientes hospitalizados, as hemoculturas devem ser consideradas para auxiliar no diagnóstico etiológico e planejamento terapêutico. O tratamento inicial deve ser iniciado empiricamente com antibióticos. Caso haja necessidade de hospitalização, hemoculturas devem ser consideradas para auxiliar na propedêutica. Após implementação das vacinas pneumocócicas, principalmente após introdução da vacina pneumocócica 13 valente (PCV 13), houve redução significativa dos casos de pneumonia bacteriana e também da necessidade hospitalização. Diante de tal realidade, a elaboração do trabalho possui como objetivo a melhora dos procedimentos e a padronização dos atendimentos da população pediátrica com um quadro clínico sugestivo pneumonia adquirida na comunidade, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), ao construir um protocolo clínico de atendimento específico para a doença. O presente trabalho objetiva elaborar um protocolo clínico de atendimento de pneumonia adquirida na comunidade no Hospital do Servidor Público Municipal de São Paulo, contribuindo na assistência médica dos pacientes pediátricos. Apesar do grande avanço com a introdução das vacinas pneumocócicas, a PAC ainda representa uma importante causa de mortalidade na população infantil, sendo fundamental a elaboração de protocolos clínicos para abordar corretamente os pacientes que recorrem a um Pronto Socorro Infantil. Protocolos clínicos são diretrizes fundamentadas nas melhores práticas para a abordagem e tratamento de determinadas doenças, baseadas em evidência científica. O presente trabalho objetiva a melhora dos procedimentos e a uniformização dos atendimentos da população pediátrica com pneumonia, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), com a construção de um protocolo clínico de atendimento específico para a doença, a partir da revisão de literatura atualizada, cujo período de vigência seguirá os progressos científicos sobre o tema. Palavras-chave: Pneumonia Adquirida da Comunidade. Protocolos clínicos. Pediatria. Serviços Médicos de Emergência. Vacinas Pneumocócicas

Fistula Salival: presentación atípica en parotiditis bacteriana, a propósito de un caso / Salival Fistula, atypical presentation of bacterial parotiditis, by the purpose of a case

Introducción: La fístula salival es la comunicaciónde la glándula salival o el conducto parotídeo hacia la piel,debido a una lesión traumática del parénquima o del conducto deexcreción; no suele ser una complicación frecuente en parotiditisaguda. El objetivo de este trabajo es destacar la presentaciónatípica de un caso de parotiditis bacteriana asociado a fistulasalival hacia el conducto auditivo externo y cavidad oral, y aparálisis facial periférica. Caso clínico: Paciente masculino de15 años de edad, quien consulta por otalgia y otorrea derechaasociado a aumento de volumen en región parotídea ipsilateralde 5 días de evolución. Al examen físico se evidencia, caraasimétrica con desviación de comisura labial hacia la izquierda ycierre palpebral completo sin esfuerzo, con aumento de volumende parótida derecha con signos de flogosis, otorrea purulentaderecha . solución de continuidad en tercio medio de pisode conducto auditivo externo. Ecosonograma de piel y partesblandas, reveló cambios inflamatorios en glándula parótida concolección de 112 cc., Los hallazgos tomográficos de oído medioy mastoides corroboraron hallazgos del ecosonograma. se realizódrenaje quirúrgico del absceso y se trató con Clindamicina600 mg vía endovenosa cada 6 horas y Penicilina Cristalina200 mg/kg/ peso cada 6 horas y su evolución fue satisfactoria.Conclusión:Los abscesos parotídeos pueden presentarse demanera atípica o en raras ocasiones con drenaje a través delconducto auditivo externo(AU)

Introduction: Salivary fistula is the communicationof the salivary glands or the parotid duct to the skin, due toa traumatic injury to the parenchyma or the excretion duct; Itis not usually a frequent complication in acute parotitis. the eobjective of this work is to highlight the atypical presentation of acase of bacterial parotitis associated with salivary fistula towardsthe external auditory canal and oral cavity, and peripheralfacial paralysis. Clinical case: A 15-year-old male patient, whoconsulted due to otalgia and right otorrhea associated with anincrease in volume in the ipsilateral parotid region of 5 days ofevolution. On physical examination, an asymmetrical face withdeviation of the lip corner to the leth and complete palpebralclosure without effort, with increased volume of the rightparotid gland with signs of phlogosis, right purulent otorrhea and continuity solution in the middle third of the external auditory canal are evident. Ultrasound of the skin and so the tissues revealed inflammatory changes in the parotid glands with a collection of 112 cc. yhe tomographic findings of the middle ear and mastoids corroborated the findings of the echosonogram; Surgical drainage of the abscess was performed and he was treated with clindamycin 600 mg intravenously every 6 hours and crystalline penicillin 200 mg/kg/weight every 6 hours, and his evolution was satisfactory. Conclusion: Parotid abscesses can present atypically or rarely with drainage through the external auditory canal(AU)

Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid.

Macrophages are important players in the maintenance of tissue homeostasis1. Perivascular and leptomeningeal macrophages reside near the central nervous system (CNS) parenchyma2, and their role in CNS physiology has not been sufficiently well studied. Given their continuous interaction with the cerebrospinal fluid (CSF) and strategic positioning, we refer to these cells collectively as parenchymal border macrophages (PBMs). Here we demonstrate that PBMs regulate CSF flow dynamics. We identify a subpopulation of PBMs that express high levels of CD163 and LYVE1 (scavenger receptor proteins), closely associated with the brain arterial tree, and show that LYVE1+ PBMs regulate arterial motion that drives CSF flow. Pharmacological or genetic depletion of PBMs led to accumulation of extracellular matrix proteins, obstructing CSF access to perivascular spaces and impairing CNS perfusion and clearance. Ageing-associated alterations in PBMs and impairment of CSF dynamics were restored after intracisternal injection of macrophage colony-stimulating factor. Single-nucleus RNA sequencing data obtained from patients with Alzheimer's disease (AD) and from non-AD individuals point to changes in phagocytosis, endocytosis and interferon-γ signalling on PBMs, pathways that are corroborated in a mouse model of AD. Collectively, our results identify PBMs as new cellular regulators of CSF flow dynamics, which could be targeted pharmacologically to alleviate brain clearance deficits associated with ageing and AD.

Calcificaciones torácicas fuera del parénquima pulmonar: una revisión / Chest calcifications beyond the lung parenchyma–a review

Objetivo: Las calcificaciones torácicas se encuentran con frecuencia en las radiografías y TC de tórax, en una gran variedad de trastornos. Si bien la mayoría de las calcificaciones son secuelas benignas de una enfermedad anterior, aportan información importante para establecer el diagnóstico. En este artículo se analizan los diferentes tipos de lesiones calcificadas halladas en el tórax, prestando especial atención a las que se sitúan fuera del parénquima pulmonar. Se utiliza un enfoque basado en la localización para el diagnóstico diferencial, a la vez que se proporcionan al lector perlas diagnósticas y se analiza la importancia clínica de los diferentes tipos de calcificaciones. Conclusión: Las calcificaciones torácicas son un hallazgo frecuente en las pruebas de imagen habituales. El conocimiento de las diferentes etiologías y manifestaciones radiológicas proporciona al radiólogo las herramientas necesarias para elaborar un diagnóstico diferencial, así como para diferenciar correctamente los hallazgos que necesitan un mayor estudio de los que pueden ser descartados.(AU)

Objective: Thoracic calcifications are frequently found in chest radiographs and CTs, occurring in a wide variety of disorders. Although most calcifications are harmless sequelae of previous disease, they provide important information to establish the diagnosis. This article reviews the different types of calcified lesions found in the chest, focusing on lesions outside the lung parenchyma. A location-based approach to the differential diagnosis is used, while providing the reader with diagnostic pearls and discussing the clinical importance of the different types of calcifications. Conclusion: Chest calcifications are a common finding in routine chest imaging. Understanding the different etiologies and radiologic manifestations provide the radiologist with the necessary tools to elaborate a differential diagnosis, as well as to correctly differentiate the findings that need further work-up from the ones that can be dismissed.(AU)

Airway and parenchymal tissue resistance and elastance in ex vivo sheep lungs: effects of bronchochallenge and deep inspiration.

Lung resistance (RL) is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in RL, but the mechanism is not entirely clear. The first step toward understanding the effect of DI is to determine how each of the resistance components is affected by DI. In the present study, we measured RL and apparent airway resistance (RAW, which combines the effects of airway resistance and airway heterogeneity) simultaneously before and after a DI in acetylcholine (ACh)-challenged ex vivo sheep lungs. We found that at normal breathing frequency (0.25 Hz) ACh-challenge led to a doubling of RL, 80.3% of that increase was caused by an increase in RAW; the increase in apparent tissue resistance (RT) was insignificant. 57.7% of the increase in RAW was abolished by a single DI. After subtracting RAW from RL, the remaining RT was mostly independent of ACh-challenge and its reduction after a DI came mostly from the change in the mechanical properties of lung parenchyma. We conclude that at normal breathing frequency, RL in an unchallenged lung is mostly composed of RT, and the increase in RL due to ACh-challenge stems mostly from the increase in RAW and that both RAW and RT can be greatly reduced by a DI, likely due to a reduction in true airway resistance and heterogeneity, as well as parenchymal tissue hysteresis post DI.

Secuestro pulmonar en pacientes adultos. Revisión de la literatura a partir de tres casos clínicos / Pulmonary sequestration in adult patients. Review of the literature from 3 clinical cases

El secuestro pulmonar es una rara enfermedad congénita del tracto respiratorio, en la cual existe un parénquima pulmonar no funcionante que presenta una circulación arterial aberrante. Puede acompañarse de otras alteraciones torácicas como enfisema lobar, el síndrome de la cimitarra o malformaciones adenomatoides quísticas. El diagnóstico en la edad adulta suele ser incidental, aunque también puede presentarse en un menor número de pacientes como infecciones respiratorias de repetición.(AU)

Pulmonary sequestration is a rare congenital disease of the respiratory tract, in which there is a non-functioning lung parenchyma that presents an aberrant arterial circulation. It can be accompanied by other thoracic alterations such as lobar emphysema, scimitar syndrome or cystic adenomatoid malformations. Diagnosis in adulthood is usually incidental, although it can also present in a smaller number of patients as recurrent respiratory infections.(AU)

Mind the gap: IgG4-related disease mimicking infectious cerebral mass lesions.

BACKGROUND: Cerebral intraparenchymal masses represent usually a neoplastic, or infectious differential diagnostic workup in neurology or infectious disease units. CASE PRESENTATION: Our patient was an 82-year-old male presenting with seizures, cerebral masses and a history of past treated pulmonary tuberculosis. Initial workup included a differential diagnosis of an infectious mass/multiple abscess. After exclusion of infectious or primary neoplastic origins by negative HIV serology, the absence of immune suppression, endocarditic lesions, negative results of blood cultures and bronchoalveolar lavage, negative cerebrospinal fluid workout on spinal tap led to exclusion of infectious causes. A surgical procedure was performed to access one of the lesions. This yielded a firm, cyst-like mass of histiocytic granulomatous tissue with a conspicuous plasmacellular component and a relevant IgG4 plasmacellular component consistent with IgG4-related disease. Steroid treatment determined conspicuous improvement and led to discharge of the patient. CONCLUSION: Parenchymal IgG4-related disease may be included as a new entity in the differential diagnosis of single or multiple cerebral masses in addition to infectious or neoplastic etiology.

MORPHOLOGICAL TRAITS OF HEPATIC PARENCHYMAL TISSUE REPAIR FOLLOWING EXPERIMENTAL INJURY.

The aim of the study was to investigate morphological traits of hepatic parenchymal tissue repair in response to injury using the conventional technique (closure) and an innovation method (such as hemostatic medication swab packing and modified batching). The experimental study was carried out on laboratory rats of the Winzar breed using light microscopy, standard stains for micropreparations, and morphometry. Histopathologic examination of micropreparations stained by standard methods revealed pronounced dystrophic processes in hepatocytes located near the necrotic zone (albuminous and hydropic degeneration and chromatin fragmentation in the nuclei). Morphometric studies showed a significant decrease (p<0.001) in almost all indicators of the size of cells and nuclei both near necrosis and distant from it on day 28 of the experiment in the experimental group in comparison to the control group. The results obtained pointed to more intense repair processes when applying the innovation method.

Utilidad del índice de fibrosis hepática (IFH) medido durante la ultrasonografía endoscópica en la evaluación del parénquima pancreático / Usefulness of the Liver Fibrosis Index (LFI) Measured during Endoscopic Ultrasonography in Evaluating the Pancreatic Parenchyma

El ultrasonido endoscópico ha cambiado la evaluación de las enfermedades pancreáticas y ha logrado un diagnóstico histopatológico (cuando se asocia con la punción); sin embargo, este procedimiento requiere de entrenamiento, no está libre de complicaciones y alrededor de 25% de los pacientes puede tener falsos negativos. Por esto se ha implementado el uso de la elastografía cuantitativa con el strain ratio, el cual permite diferenciar las masas benignas de las malignas. Existe evidencia creciente, pero aún no conclusiva, dada la heterogeneidad de los resultados (sin consenso para su realización), por lo que es necesario desarrollar otros métodos, que permitan una mayor certeza diagnóstica, como el índice de fibrosis hepática (IFH) medido por ultrasonografía endoscópica, el cual tienen como base la inteligencia artificial, validado para el diagnóstico y el seguimiento de la fibrosis hepática. Nuestro grupo considera que se podría usar de la misma forma para valorar el parénquima pancreático. Objetivo: evaluar si el IFH puede diferenciar tres tipos diferentes de tejidos pancreáticos: páncreas normal, páncreas graso y cáncer de páncreas. Metodología: estudio prospectivo de corte transversal en un solo centro. Se incluyeron 66 pacientes mayores de 18 años, con indicación de ultrasonografía endoscópica. El grupo 1 fue de pacientes con indicación diferente a la enfermedad biliopancreática (55 pacientes). En este grupo se aplicó la escala de clasificación de páncreas graso por ultrasonografía endoscópica (USE), utilizando como referencia la ecogenicidad del bazo (previamente validada); este grupo se subdividió en uno con parénquima pancreático normal y en otro con páncreas graso. En el grupo 2 (11 pacientes) se incluyeron los pacientes llevados para el estudio de lesión sólida pancreática, con diagnóstico citológico positivo para carcinoma de páncreas. Como herramienta de recolección de datos se utilizó un formulario virtual de Google Drive, disponible con dirección acortada: shorturl.at/pIMWX, diligenciado antes y después del procedimiento por fellows de Gastroenterología, previamente entrenados para este fin. El IFH se tomó en el páncreas en tiempo real mediante un software suministrado por el fabricante (Hitachi-Noblus), en un período comprendido entre enero de 2019 y enero 2020. A todos los pacientes se les realizó una ecoendoscopia biliopancreática completa, con un ecoendoscopio Pentax lineal y procesador Hitachi-Noblus; luego se efectuó una elastografía cualitativa y una cuantitativa, la cual incluyó la medición del IFH. Resultados: en total se incluyeron 66 pacientes: 11 pacientes con diagnóstico confirmado por citología de cáncer de páncreas y 55 pacientes que se enviaron para ecoendoscopia por evaluación de otras patologías diferentes a la biliopancreática. El rango de edad fue de 23-89, media de 56,75 años. El antecedente más frecuente fue la esteatosis o esteatohepatitis (n = 14) (25,45%). La indicación para la realización del procedimiento más frecuente fue la lesión subepitelial (n = 29) (52,73 %). Los porcentajes de pacientes según los grados de ecogenicidad del páncreas fueron de grado I (n = 29) (52,73 %); grado II (n = 5) (9,09 %); grado III (n = 18) (32,73 %); grado IV (n = 3) (5,45 %). Se tomaron los grados I y II como páncreas normal, y los grado III y IV como páncreas graso. Estos se dividieron en n = 34 pacientes (61,82 %) para páncreas normal y n = 21 (38 %) para páncreas graso; es decir, que de acuerdo con la escala utilizada hay una prevalencia para páncreas graso de 38,18 %. Se realizó el IFH en los tres subgrupos diferentes: los considerados como ecoendoscópicamente normales, los clasificados como páncreas graso y los pacientes con diagnóstico de cáncer de páncreas confirmado por citología, tomado en el páncreas. El IFH para los tres diferentes grupos fueron, respectivamente, normal: IFH 2,60, rango 0,97-3,47 (IC 95 % 2,17-3,02); páncreas graso: IFH 3,87, rango 2-5,5 (IC 95 % 3,44-4,29); cáncer de páncreas: IFH 6,35, rango 5,8-7,8 (IC 95 % 5,92-6,77). Conclusiones: este es el primer estudio piloto que usa el IFH aplicado al parénquima pancreático, y se sugiere su utilidad para diferenciar, de manera no invasiva, el páncreas normal, el graso y el carcinoma de páncreas. Este hallazgo se debe confirmar en poblaciones más amplias y heterogéneas, con el fin de ser validado.

Abstract Endoscopic ultrasound has changed the evaluation of pancreatic diseases and has achieved a histopathological diagnosis (when associated with a puncture); however, this procedure requires training, is not free of complications, and around 25 % of patients may have false negatives. Therefore, quantitative elastography with the strain ratio has been implemented to differentiate benign masses from malignant ones. There is growing but not yet conclusive evidence, given the heterogeneity of the results (without consensus on its performance). It is necessary to develop other methods that allow for greater diagnostic certainty, such as the liver fibrosis index (LFI) measured by endoscopic ultrasonography. This method is based on artificial intelligence and validated for diagnosing and monitoring liver fibrosis. Our group considers that it could also be used to assess the pancreatic parenchyma. Aim: To evaluate whether the LFI can differentiate three types of pancreatic tissues: normal pancreas, fatty pancreas, and pancreatic cancer. Materials and methods: Prospective cross-sectional single-center study. We included sixty-six patients over 18 years of age with an indication for endoscopic ultrasonography. Group 1 consisted of patients with an indication other than the biliopancreatic disease (55 patients). The endoscopic ultrasonography (EUS) fatty pancreas classification scale was applied to this group, taking the echogenicity of the spleen (previously validated) as a reference; this group was subdivided into normal pancreatic parenchyma and fatty pancreas. Group 2 (11 patients) included those examined for solid pancreatic lesions with a positive cytological diagnosis of pancreatic carcinoma. We used a Google Form as a data collection tool, available with a shortened address (shorturl.at/pIMWX). It was filled out before and after the procedure by Gastroenterology fellows, previously trained for this purpose. The LFI was measured in the pancreas in real-time using software supplied by the manufacturer (Hitachi Noblus) between January 2019 and January 2020. All patients underwent a complete biliopancreatic echoendoscopy, with a linear Pentax echoendoscope and Hitachi Noblus processor. Then, qualitative and quantitative elastography was performed, including LFI measurement. Results: We included a total of 66 patients: 11 with a diagnosis of pancreatic cancer confirmed by cytology and 55 sent for ultrasound endoscopy due to pathologies other than the biliopancreatic disease. The age range was 23-89, with a mean of 56.75 years. The most frequent history was steatosis or steatohepatitis (n = 14) (25.45 %). The most frequent indication for performing the procedure was subepithelial lesion (n = 29) (52.73 %). The percentages of patients according to pancreatic echogenicity were Grade I (n = 29) (52.73 %); Grade II (n = 5) (9.09 %); Grade III (n = 18) (32.73 %); Grade IV (n = 3) (5.45 %). Grades I and II were taken as a normal pancreas and Grades III and IV as a fatty pancreas, divided into n = 34 patients (61.82 %) for a normal pancreas and n = 21 (38 %) for a fatty pancreas. According to the scale used, there is a fatty pancreas prevalence of 38.18 %. The LFI was measured in three subgroups: those considered endoscopically normal, those classified as fatty pancreas, and patients diagnosed with pancreatic cancer confirmed by cytology taken from the pancreas. The LFI for these groups were, respectively, normal pancreas: LFI 2.60, range 0.97-3.47 (95 % CI 2.17-3.02); fatty pancreas: LFI 3.87, range 2-5.5 (95 % CI 3.44-4.29); pancreatic cancer: LFI 6.35, range 5.8-7.8 (95 % CI 5.92-6.77). Conclusions: This is the first pilot study that applies the LFI to the pancreatic parenchyma. It is useful in differentiating a normal pancreas, a fatty pancreas, and pancreatic carcinoma non-invasively. This finding must be validated in larger and more heterogeneous populations.

Angiosarcoma radioinducido de mama: reporte de caso / Radioinduced angiosarcoma of the breast: Case report / Angiossarcoma radioinduzido de mama: reporte de caso

El angiosarcoma es un tumor vascular maligno poco frecuente. Constituye menos del 2% de todos los sarcomas. Existen varias formas clínicas, una es la producida después de radioterapia, en pacientes que fueron tratadas por un cáncer de mama, con cirugía conservadora y radioterapia. Se presenta como un sarcoma de alto grado, localizado en la piel o en el tejido subcutáneo y, ocasionalmente, el parénquima mamario. El único tratamiento curativo es la cirugía, con tendencia a la recurrencia y a hacer metástasis hematógena, el pronóstico es malo, con alta tasa de mortalidad.

Angiosarcoma is a rare malignant vascular tumor. It constitutes less than 2% of all sarcomas. There are several clinical forms; the one produced after radiation therapy is that associated with patients who were treated for breast cancer with conservative surgery and radiation therapy. It presents as a high-grade sarcoma located on the skin or the subcutaneous tissue and, occasionally, the breast parenchyma. The only curative treatment is surgery, with a tendency to recurrence and visceral hematogenous metastasis, with a poor prognosis and a high mortality rate.

El angiossarcoma é um tumor vascular maligno pouco frequente. Constitui menos de 2% de todos os sarcomas. Existem várias formas clínicas, uma é a produzida depois da radioterapia, em pacientes que foram tratadas por um câncer de mama, com cirurgia conservadora e radioterapia. Se apresenta como um sarcoma de alto grau, localizado na pele ou no tecido subcutâneo e, ocasionalmente, o parênquima mamário. O único tratamento curativo é a cirurgia, com tendência à recorrência e a fazer metástasehematogênica, o prognóstico é mau, com alta taxa de mortalidade.

Interferon gamma constrains type 2 lymphocyte niche boundaries during mixed inflammation.

Allergic immunity is orchestrated by group 2 innate lymphoid cells (ILC2s) and type 2 helper T (Th2) cells prominently arrayed at epithelial- and microbial-rich barriers. However, ILC2s and Th2 cells are also present in fibroblast-rich niches within the adventitial layer of larger vessels and similar boundary structures in sterile deep tissues, and it remains unclear whether they undergo dynamic repositioning during immune perturbations. Here, we used thick-section quantitative imaging to show that allergic inflammation drives invasion of lung and liver non-adventitial parenchyma by ILC2s and Th2 cells. However, during concurrent type 1 and type 2 mixed inflammation, IFNγ from broadly distributed type 1 lymphocytes directly blocked both ILC2 parenchymal trafficking and subsequent cell survival. ILC2 and Th2 cell confinement to adventitia limited mortality by the type 1 pathogen Listeria monocytogenes. Our results suggest that the topography of tissue lymphocyte subsets is tightly regulated to promote appropriately timed and balanced immunity.

Microdialysis and CO2 sensors detect pancreatic ischemia in a porcine model.

BACKGROUND: Pancreatic transplantation is associated with a high rate of early postoperative graft thrombosis. If a thrombosis is detected in time, a potentially graft-saving intervention can be initiated. Current postoperative monitoring lacks tools for early detection of ischemia. The aim of this study was to investigate if microdialysis and tissue pCO2 sensors detect pancreatic ischemia and whether intraparenchymal and organ surface measurements are comparable. METHODS: In 8 anaesthetized pigs, pairs of lactate monitoring microdialysis catheters and tissue pCO2 sensors were simultaneously inserted into the parenchyma and attached to the surface of the pancreas. Ischemia was induced by sequential arterial and venous occlusions of 45-minute duration, with two-hour reperfusion after each occlusion. Microdialysate was analyzed every 15 minutes. Tissue pCO2 was measured continuously. We investigated how surface and parenchymal measurements correlated and the capability of lactate and pCO2 to discriminate ischemic from non-ischemic periods. RESULTS: Ischemia was successfully induced by arterial occlusion in 8 animals and by venous occlusion in 5. During all ischemic episodes, lactate increased with a fold change of 3.2-9.5 (range) in the parenchyma and 1.7-7.6 on the surface. Tissue pCO2 increased with a fold change of 1.6-3.5 in the parenchyma and 1.3-3.0 on the surface. Systemic lactate and pCO2 remained unchanged. The area under curve (AUC) for lactate was 0.97 (95% confidence interval (CI) 0.93-1.00) for parenchymal and 0.90 (0.83-0.97) for surface (p<0.001 for both). For pCO2 the AUC was 0.93 (0.89-0.96) for parenchymal and 0.85 (0.81-0.90) for surface (p<0.001 for both). The median correlation coefficients between parenchyma and surface were 0.90 (interquartile range (IQR) 0.77-0.95) for lactate and 0.93 (0.89-0.97) for pCO2. CONCLUSIONS: Local organ monitoring with microdialysis and tissue pCO2 sensors detect pancreatic ischemia with adequate correlation between surface and parenchymal measurements. Both techniques and locations seem feasible for further development of clinical pancreas monitoring.