RESUMEN

Pathologists face many challenges when diagnosing sclerosing biliary lesions on liver biopsy. First, histologic findings tend to be nonspecific with similar to identical features seen in numerous conditions, from benign to outright malignant. In addition, the patchy nature of many of these entities amplifies the inherent limitations of biopsy sampling. The end result often forces pathologists to issue descriptive sign outs that require careful clinical correlation; however, certain clinical, radiologic, and histologic features may be of diagnostic assistance. In this article, we review key elements of four sclerosing biliary processes whose proper identification has significant prognostic and therapeutic implications.

Asunto(s)

Colangitis Esclerosante , Humanos , Colangitis Esclerosante/diagnóstico , Colangitis Esclerosante/patología , Inmunoglobulina G , Biopsia , Diagnóstico Diferencial

RESUMEN

INTRODUCTION AND IMPORTANCE: Heterotopic Pancreas (HP) is defined by the presence of pancreatic tissue in an anatomically distinct location from the main pancreas. While often clinically silent, it may present symptomatically. If located in the gastric antrum, HP may cause gastric outlet obstruction (GOO). The objective of this paper is to present a rare case of HP in the gastric antrum causing GOO. CASE PRESENTATION: Herein, we report a 43-year-old man who presented with abdominal pain and non-bilious emesis in the setting of COVID-19 infection and alcohol consumption. During the initial workup, computed-tomography (CT) was non-specific but demonstrated GOO, concerning for cancer. Cold forceps biopsies taken during esophagogastroduodenoscopy (EGD) confirmed benign HP. Since the patient was symptomatic from gastric outlet compression, he underwent resection via laparoscopic distal gastrectomy and Billroth II gastrojejunostomy. At 1-month postoperative follow-up, the patient recovered uneventfully. We hypothesized that GOO by HP in this case may have been associated with cumulative effects of alcohol consumption and COVID-19 infection on the ectopic tissue. CLINICAL DISCUSSION: HP is rare and difficult to diagnose preoperatively. When located in gastric antrum, HP can cause GOO, mimicking gastric malignancy. Combination of EGD/EUS, biopsy/FNA, and surgical resection are necessary to definitively make the diagnosis. Finally, it is important to consider that heterotopic pancreatitis or structural changes in HP may occur due to classic pancreatic stressors like alcohol and viral infections. CONCLUSION: HP may cause GOO presenting with non-bilious emesis and abdominal pain, mistaken for malignancy on CT imaging.

RESUMEN

Invasive fungal infections are increasing in prevalence because of an expanding population of immunocompromised individuals. To reduce morbidity and mortality, it is critical to accurately identify fungal pathogens to guide treatment. Current methods rely on histopathology, fungal culture, and serology, which are often insufficient for diagnosis. Herein, we describe the use of a laboratory-developed internal transcribed spacer-targeted amplicon-based next-generation sequencing (NGS) assay for the identification of fungal etiology in fungal stain-positive formalin-fixed, paraffin-embedded tissues by using Illumina MiSeq. A total of 44 specimens from 35 patients were included in this study, with varying degrees of fungal burden from multiple anatomic sites. NGS identified 20 unique species across the 54 total organisms detected, including 40 molds, 10 yeasts, and 4 dimorphic fungi. The histopathologic morphology and the organisms suspected by surgical pathologist were compared with the organisms identified by NGS, with 100% (44/44) and 93.2% (41/44) concordance, respectively. In contrast, fungal culture only provided an identification in 27.3% (12/44) of specimens. We demonstrated that NGS is a powerful method for accurate and unbiased fungal identification in formalin-fixed, paraffin-embedded tissues. A retrospective evaluation of the clinical utility of the NGS results also suggests this technology can potentially improve both the speed and the accuracy of diagnosis for invasive fungal infections.

Asunto(s)

Formaldehído/química , Hongos/aislamiento & purificación , Secuenciación de Nucleótidos de Alto Rendimiento , Adhesión en Parafina , Patología , Fijación del Tejido , Humanos

RESUMEN

Patients with flow-dependent aortopulmonary collateral arteries often exhibit tenuous clinical statuses. Here we present an infant with Tetralogy of Fallot with pulmonary atresia (TOF-PA) and major aortopulmonary collateral arteries (MAPCAs) who experienced clinically significant oxygen desaturations during feedings. These frequent episodes were attributed to gastroesophageal reflux. In preparation for possible surgical correction of her complex congenital heart condition, she was intubated for a cardiac catheterization to better characterize her anatomy, but terminally decompensated shortly after extubation and restarting feeding. On autopsy, very mild evidence of esophageal reflux was present; instead, one of her four aortopulmonary collateral arteries was unexpectedly discovered traversing through the muscular layer of her esophageal wall. This finding was confirmed microscopically with significant intimal hyperplasia compared to uninvolved collateral arteries. The remainder of the autopsy findings, including her myocardium, lungs, and esophagus, were unremarkable. Given the feeding-associated oxygen desaturations present in life and the aberrant collateral artery's comparative stenosis at death, we speculate that the repetitive trauma of esophageal peristalsis was not only significant enough to temporarily impact oxygenation but, over time, led to near-occlusion of the intraesophageal collateral artery, which may have contributed to the terminal decompensation of this already tenuous patient.

Asunto(s)

Aorta Torácica/anomalías , Arteriopatías Oclusivas/etiología , Circulación Colateral , Displasia Fibromuscular/complicaciones , Arteria Pulmonar/anomalías , Circulación Pulmonar , Tetralogía de Fallot/complicaciones , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Arteriopatías Oclusivas/fisiopatología , Autopsia , Biopsia , Causas de Muerte , Resultado Fatal , Femenino , Displasia Fibromuscular/fisiopatología , Humanos , Lactante , Angiografía por Resonancia Magnética , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Tetralogía de Fallot/fisiopatología

RESUMEN

Ozone is an atmospheric pollutant that causes lung inflammation and airway hyperresponsiveness. Ozone's effects occur in two distinct phases that are mediated by different populations of eosinophils. In the acute phase 1 day after exposure, mature airway-resident eosinophils alter parasympathetic nerve function that results in airway hyperresponsiveness. At this time point, the severity of hyperresponsiveness correlates with the number of eosinophils in close proximity to airway nerves, but not with eosinophils in bronchoalveolar lavage. Three days later, newly divided eosinophils are recruited to airways by a tumor necrosis factor-α-dependent mechanism. These new eosinophils paradoxically attenuate ozone-induced airway hyperresponsiveness. Ozone's effects on airway tissue eosinophils and nerve-associated eosinophils 3 days after exposure are unknown. Thus, we tested ozone's effects on eosinophils in airway subepithelium and around airway nerves 1 and 3 days after ozone in nonsensitized and ovalbumin-sensitized guinea pigs with or without the tumor necrosis factor-α antagonist, etanercept, and compared changes in eosinophils with ozone-induced airway hyperresponsiveness. More eosinophils were present in small, noncartilaginous airways and along small airway nerves compared to large cartilaginous airways in all treatment groups. The number of airway and nerve-associated eosinophils were unaffected 1 day after ozone exposure, whereas significantly fewer airway eosinophils were present 3 days later. Airway and nerve-associated eosinophils were also decreased in small airways 3 days after ozone in sensitized animals. These changes were blocked by etanercept. Airway eosinophils, but not nerve-associated or bronchoalveolar lavage eosinophils correlated with airway hyperresponsiveness 3 days after ozone. Our findings indicate ozone causes persistent alterations in airway eosinophils and reinforce the importance of characterizing eosinophils' effects within distinct airway compartments.

Asunto(s)

Asma/inmunología , Movimiento Celular , Eosinófilos/efectos de los fármacos , Ozono/efectos adversos , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Asma/etiología , Asma/patología , Eosinófilos/inmunología , Eosinófilos/fisiología , Etanercept/farmacología , Femenino , Cobayas , Inmunosupresores/farmacología , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología , Sistema Respiratorio/inervación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores

RESUMEN

The vertebrate heart muscle (myocardium) develops from the first heart field (FHF) and expands by adding second heart field (SHF) cells. While both lineages exist already in teleosts, the primordial contributions of FHF and SHF to heart structure and function remain incompletely understood. Here we delineate the functional contribution of the FHF and SHF to the zebrafish heart using the cis-regulatory elements of the draculin (drl) gene. The drl reporters initially delineate the lateral plate mesoderm, including heart progenitors. Subsequent myocardial drl reporter expression restricts to FHF descendants. We harnessed this unique feature to uncover that loss of tbx5a and pitx2 affect relative FHF versus SHF contributions to the heart. High-resolution physiology reveals distinctive electrical properties of each heart field territory that define a functional boundary within the single zebrafish ventricle. Our data establish that the transcriptional program driving cardiac septation regulates physiologic ventricle partitioning, which successively provides mechanical advantages of sequential contraction.

Asunto(s)

Atrios Cardíacos/embriología , Ventrículos Cardíacos/embriología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas de Pez Cebra/genética , Animales , Animales Modificados Genéticamente , Cadherinas/genética , Cadherinas/metabolismo , Embrión no Mamífero , Regulación del Desarrollo de la Expresión Génica , Corazón/embriología , Atrios Cardíacos/metabolismo , Ventrículos Cardíacos/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Proteínas de Unión a TGF-beta Latente/genética , Proteínas de Unión a TGF-beta Latente/metabolismo , Mesodermo/embriología , Mesodermo/metabolismo , Cadenas Ligeras de Miosina/genética , Cadenas Ligeras de Miosina/metabolismo , Elementos Reguladores de la Transcripción/genética , Proteínas y Péptidos Salivales/genética , Proteínas y Péptidos Salivales/metabolismo , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Pez Cebra , Proteínas de Pez Cebra/metabolismo

RESUMEN

BACKGROUND: Linear DNA-based and Tol2-mediated transgenesis are powerful tools for the generation of transgenic zebrafish. However, the integration of multiple copies or transgenes at random genomic locations complicates comparative transgene analysis and makes long-term transgene stability unpredictable with variable expression. Targeted, site-directed transgene integration into pre-determined genomic loci can circumvent these issues. The phiC31 integrase catalyzes the unidirectional recombination reaction between heterotypic attP and attB sites and is an efficient platform for site-directed transgenesis. RESULTS: We report the implementation of the phiC31 integrase-mediated attP/attB recombination for site-directed zebrafish transgenics of attB-containing transgene vectors into single genomic attP landing sites. We generated Tol2-based single-insertion attP transgenic lines and established their performance in phiC31 integrase-catalyzed integration of an attB-containing transgene vector. We found stable germline transmission into the next generation of an attB reporter transgene in 34% of all tested animals. We further characterized two functional attP landing site lines and determined their genomic location. Our experiments also demonstrate tissue-specific transgene applications as well as long-term stability of phiC31-mediated transgenes. CONCLUSIONS: Our results establish phiC31 integrase-controlled site-directed transgenesis into single, genomic attP sites as space-, time-, and labor-efficient zebrafish transgenesis technique. The described reagents are available for distribution to the zebrafish community.

Asunto(s)

Técnicas de Transferencia de Gen , Integrasas/genética , Proteínas de Pez Cebra/genética , Pez Cebra/genética , Animales , Animales Modificados Genéticamente