Intervertebral disc cell chondroptosis elicits neutrophil response in Staphylococcus aureus spondylodiscitis.

To understand the pathophysiology of spondylodiscitis due to Staphylococcus aureus, an emerging infectious disease of the intervertebral disc (IVD) and vertebral body with a high complication rate, we combined clinical insights and experimental approaches. Clinical data and histological material of nine patients suffering from S. aureus spondylodiscitis were retrospectively collected at a single center. To mirror the clinical findings experimentally, we developed a novel porcine ex vivo model mimicking acute S. aureus spondylodiscitis and assessed the interaction between S. aureus and IVD cells within their native environment. In addition, the inflammatory features underlying this interaction were assessed in primary human IVD cells. Finally, mirroring the clinical findings, we assessed primary human neutrophils for their ability to respond to secreted inflammatory modulators of IVD cells upon the S. aureus challenge. Acute S. aureus spondylodiscitis in patients was characterized by tissue necrosis and neutrophil infiltration. Additionally, the presence of empty IVD cells' lacunae was observed. This was mirrored in the ex vivo porcine model, where S. aureus induced extensive IVD cell death, leading to empty lacunae. Concomitant engagement of the apoptotic and pyroptotic cell death pathways was observed in primary human IVD cells, resulting in cytokine release. Among the released cytokines, functionally intact neutrophil-priming as well as broad pro- and anti-inflammatory cytokines which are known for their involvement in IVD degeneration were found. In patients as well as ex vivo in a novel porcine model, S. aureus IVD infection caused IVD cell death, resulting in empty lacunae, which was accompanied by the release of inflammatory markers and recruitment of neutrophils. These findings offer valuable insights into the important role of inflammatory IVD cell death during spondylodiscitis and potential future therapeutic approaches.

The role of macrophages type 2 and T-regs in immune checkpoint inhibitor related adverse events.

Immune checkpoint inhibitory (ICI) therapy represents a novel approach in a variety of cancers, with impressive survival benefit. With ICIs, however, a new spectrum of immune related adverse events (irAE) including life threatening hypohysitis has emerged. This autopsy study aimed to investigate inflammatory cells, PD-1 and PD-L1 expression in cases of patients who developed hypophysitis and involvement of other organs. We analysed 6 patients, who were treated with ICIs and developed hypophysitis. Two received an additional MAP-kinase inhibitor, MEK-inhibitor and cytotoxic chemotherapy. Besides the pituitary gland, all investigated adrenal glands (5/5) were affected; three cases had other organs involved (liver (2/6), thyroid (2/6), lung (1/6), myocardium (1/6), colon (1/6). The inflammatory cells of involved organs were further specified and PD1 and PDL-1 expression was analyzed using immunohistochemistry. We observed that patients treated with ICIs alone showed T-cell predominant lymphocytic infiltrates, whereas patients receiving additional therapies demonstrated an increase in B- and T-lymphocytes. Surprisingly, the dominant inflammatory population was not T-cell, but type 2 macrophages. CD25 positive T-regs were sparse or absent. Our study suggests that T cell activation is only partially responsible for irAE. ICI therapy interaction with CTLA-4, PD-1 and PDL-1 in type 2 macrophages appears to result in disturbance of their control. Furthermore, depletion of T-regs seems to contribute significantly. Our findings with simultaneous pituitary and adrenal gland involvement underlines the systemic involvement as well as the importance of monitoring cortisol levels to avoid potentially life threatening hypocortisolism.

Congenital peribronchial myofibroblastic tumor: a case report.

We describe a rare occurrence of congenital peribronchial myofibroblastic tumor of the lung presenting in early fetal life. A female patient in the 24th week of gestation who presented with polyhydramnios was admitted for examination. Ultrasound examination revealed a mass compromising the lungs. Because the intrauterine fetal death was revealed by the ultrasound, delivery was induced. Necropsy revealed a pulmonary lesion compromising the left lower pulmonary lobe together with hepatomegaly. Microscopic analysis of the lung showed a lesion with a storiform arrangement of spindle cells with focal peribronchial distribution. Hepatic architecture was diffusely altered by fibrotic tissue. Immunohistochemical analysis on the pulmonary lesion showed high vimentin positivity in the fusocellular components, pointing to the mesenchymal nature of the lesion. Significant differentiation of smooth muscle tissue, as indicated by high HHF35 positivity, was also observed. Electron microscopy on the pulmonary lesion revealed elongated cells with some cytoplasmatic processes, a finding that is also compatible with mesenchymal differentiation.

Pseudotumor inflamatório de fígado: relato de caso / Inflammatory pseudotumor of the liver: case report

Pseudotumor inflamatório é lesão benigna rara que pode se desenvolver em uma grande variedade de órgãos. Sua importância na prática médica reside na dificuldade de distingui-lo de condições malignas...

Inflammatory pseudotumor is a rare benign lesion which can occur in a great variety of organs. The diagnosis is difficult to be made because it is similar in appearance to malignant entities...