We present the case of a caseous calcification of the mitral annulus, responsible for two strokes, in a 72-year-old female patient. The brain computed tomography (CT) scan confirmed the presence of a calcific embolus. The echocardiography showed a liquidy, pseudotumoral mass combined with numerous calcifications located in the posterior part of the mitral annulus and extending toward the inferior surface of the left ventricle. During surgery, we found a direct communication between the caseous necrosis and the lumen of the left ventricle at the level of its inferior wall. We performed a valve repair procedure and excision of the caseous necrosis, combined with injection of bioglue into the cavity, to avoid recurrence. Six months after the procedure, the patient was in good health, and had no recurrence of stroke with a satisfactory echocardiography. This is the first description of spontaneous fistulization of a caseous necrosis in the lumen of the left ventricle, explaining a new mechanism for cerebral embolism during the course of calcifying diseases of the mitral annulus.

Anaplastic thyroid carcinoma (ATC) is a rare and undifferentiated form of thyroid cancer. Its prognosis is poor: the median overall survival (OS) of patients varies from 4 to 10 months after diagnosis. However, a doubling of the OS time may be possible owing to a more systematic use of molecular tests for targeted therapies and integration of fast-track dedicated care pathways for these patients in tertiary centers. The diagnostic confirmation, if needed, requires an urgent biopsy reread by an expert pathologist with additional immunohistochemical and molecular analyses. Therapeutic management, defined in multidisciplinary meetings, respecting the patient’s choice, must start within days following diagnosis. For localized disease diagnosed after primary surgical treatment, adjuvant chemo-radiotherapy is recommended. In the event of locally advanced or metastatic disease, the prognosis is very poor. Treatment should then involve chemotherapy or targeted therapy and decompressive cervical radiotherapy. Here we will review current knowledge on ATC and provide perspectives to improve the management of this deadly disease.

Gene therapy represents a feasible strategy to treat inherited monogenic diseases and intramuscular (i.m.) injection of recombinant adeno-associated viral (AAV) vector is now recognized as a convenient and safe method of gene transfer. However, this approach is hampered by immune responses directed against the vector and against the transgenic protein. We used here to reproduce this situation a mouse model where robust immune responses are induced following injection of an AAV vector coding for an immunogenic transgenic protein. We show that prophylactic oral administration of the immunogenic protein before AAV-mediated gene transfer completely prevented antibody formation and cytotoxic CD8(+) T-cell response. Consistently, prophylactic oral-tolerization considerably improved long-term transgene persistence and expression. Mechanistically, inhibition of the cytotoxic immune response involved abortive proliferation of antigen-specific cytotoxic CD8(+) T cells, upregulation of the PD-1 immunoregulatory molecule, downregulation of the Bcl-2 antiapoptotic factor, and their deletion in the context of AAV-mediated gene transfer. Hence, gene therapy may represent an ideal situation where oral-tolerization can be adopted before or at the same time as vector injection to efficiently prevent deleterious immune responses directed against the transgenic protein.

Bilateral adrenal hyperplasia is a rare cause of Cushing’s syndrome. Micronodular adrenal hyperplasia, including the primary pigmented micronodular adrenal dysplasia (PPNAD) and the isolated micronodular adrenal hyperplasia (iMAD), can be distinguished from the primary bilateral macronodular adrenal hyperplasia (PBMAH) according to the size of the nodules. They both lead to overt or subclinical CS. In the latter case, PPNAD is usually diagnosed after a systematic screening in patients presenting with Carney complex, while for PBMAH, the diagnosis is often incidental on imaging. Identification of causal genes and genetic counseling also help in the diagnoses. This review discusses the last decades’ findings on genetic and molecular causes of bilateral adrenal hyperplasia, including the several mechanisms altering the PKA pathway, the recent discovery of ARMC5, and the role of the adrenal paracrine regulation. Finally, the treatment of bilateral adrenal hyperplasia will be discussed, focusing on current data on unilateral adrenalectomy.

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Exfoliative erythroderma is a rare presentation of psoriasis in children and adults. We report a 9-year-old girl with exfoliative erythroderma secondary to plaque-type psoriasis who developed hypothalamic-pituitary-adrenal axis suppression resulting from topical treatment with a medium-potency glucocorticoid. This case emphasizes the need for awareness of this potentially life-threatening complication of topical glucocorticoid use, particularly in patients who have significant compromise of barrier function secondary to widespread skin disease.

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