The overall quality of evidence of recommendations surrounding nutrition and diet in inflammatory bowel disease.

BACKGROUND AND AIM: Recently, there has been an increased focus on the role nutrition and diet play in maintaining health in inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on nutrition/diet in IBD. METHODS: A systematic search was performed on multiple databases from inception until January 1, 2021, to identify guidelines pertaining to nutrition or diet in IBD. All guidelines were reviewed for disclosure of conflicts of interest (COI) and funding, recommendation quality and strength, external document review, patient representation, and plans for update-as per Institute of Medicine (IOM) standards. In addition, recommendations and their quality were compared between guidelines/societies.​ RESULTS: Seventeen distinct societies and a total of 228 recommendations were included. Not all guidelines provided recommendations on key aspects of diet-such as the role of supplements or the appropriate micro/macro nutrition in IBD. Fifty-nine percent of guidelines reported on COI, 24% underwent external review, and 41% included patient representation. 18.4%, 25.9%, and 55.7% of recommendations were based on high-, moderate-, and low-quality evidence, respectively. 10.5%, 24.6%, and 64.9% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence (p = 0.12) and strong recommendations (p = 0.83) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of diet/nutrition in IBD. As over 50% of recommendations are based on low-quality evidence, further studies on nutrition/diet in IBD are warranted to improve the overall quality of evidence.

Androgen Receptor Signaling and the Emergence of Lethal Neuroendocrine Prostate Cancer With the Treatment-Induced Suppression of the Androgen Receptor: A Literature Review.

Androgen receptor signaling primarily influences both the normal growth and proliferation of the prostate gland and the development of prostatic carcinoma. While localized prostate cancers are typically managed with definitive therapies like surgery and radiotherapy, many patients have recurrences in the form of metastatic disease. Androgen deprivation therapy, by way of castration via orchiectomy or with drugs like luteinizing hormone-releasing hormone (commonly called gonadotropin-releasing hormone) agonists and luteinizing hormone-releasing hormone antagonists, is the primary mode of therapy for advanced castration-sensitive prostate cancer. Castration resistance invariably develops in these patients. Further treatment has shifted to newer anti-androgen drugs like enzalutamide or abiraterone and taxane-based chemotherapy. Prolonged inhibition of the androgen receptor signaling pathway causes androgen receptor-independent clonal evolution which leads to the development of treatment-emergent neuroendocrine prostate cancer. All prostate cancers at the initial presentation should undergo evaluation for the markers of neuroendocrine differentiation. Detection of serum biomarkers of neuroendocrine differentiation and circulating tumor cells is a prospective non-invasive method of detecting neuroendocrine transdifferentiation in patients undergoing treatment with androgen receptor pathway inhibitors. It is essential to perform a biopsy in the presence of red flags of neuroendocrine differentiation. Alisertib, an Aurora kinase inhibitor, showed promising clinical benefit in a subgroup of patients with certain molecular alterations. A thorough understanding of the molecular and clinical programming of treatment-emergent neuroendocrine prostate cancer can potentially lead to the development of drugs to prevent the development of this lethal variant of prostate cancer.

Hypothalamic-Pituitary Axis Dysfunction, Central Diabetes Insipidus, and Syndrome of Inappropriate Antidiuretic Hormone Secretion as the First Clinical Presentation of Neurosarcoidosis: Why Early Diagnosis and Treatment is Important?

Sarcoidosis is defined by granuloma formation in a multitude of organs. Despite its rare involvement in the nervous system, there are a number of cases that identify neurological symptoms to be the initial clinical manifestation of sarcoidosis. The involvement of the hypothalamic-pituitary (HP) axis presented most frequently with hormone deficiencies. Studies have reported that damage to the pituitary gland may be irreversible, and hormone abnormalities were generally permanent. Neurosarcoidosis has been described as the underlying cause of central diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone (SIADH) secretion. The pathological mechanism that can lead both to deficiency and excess of antidiuretic hormone (ADH) secretion is still not fully understood. It has been shown that diagnosis of neurosarcoidosis remains challenging, as symptoms can be inconclusive and diagnostic tools are not sufficiently sensitive and specific. Early treatment may potentially reverse pituitary deficiencies, although studies to confirm this hypothesis are minimal. This review article aims to increase knowledge about central DI and SIADH caused by neurosarcoidosis, identify possible difficulties in diagnosis, and discuss the importance of early management. Clinical trials investigating the long-term therapeutic response in patients with HP sarcoidosis are essential, as there are currently no established guidelines for the treatment of neurosarcoidosis.