Journal of internal medicine
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Hereditary angioedema (HAE) is a rare, potentially life-threatening genetic disorder characterized by recurrent attacks of swelling. Local vasodilation and vascular leakage are stimulated by the vasoactive peptide bradykinin, which is excessively produced due to dysregulation of the activated factor XII (FXIIa)-driven kallikrein-kinin system. There is a need for novel treatments for HAE that provide greater efficacy, improved quality of life, minimal adverse effects, and reduced treatment burden over current first-line therapies. ⋯ We highlight that there is a range of FXIIa inhibitors in development for different therapeutic areas. Of these, garadacimab, an FXIIa-targeted inhibitory monoclonal antibody, is the most advanced and has shown potential as a novel long-term prophylactic treatment for patients with HAE in clinical trials. The evidence from these trials is summarized and discussed, and we propose areas for future research where targeting FXIIa may have therapeutic potential beyond HAE.
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Hypertensive disorders of pregnancy (HDP), especially preeclampsia, and diabetes during pregnancy pose significant risks for both maternal and infant health, extending to long-term outcomes such as early-onset cardiovascular disease and metabolic disorders. Current strategies for managing HDP focus on screening, prevention, surveillance, and timely intervention. No disease-modifying therapies exist so far for established preeclampsia; delivery remains the definitive resolution. ⋯ Advancements in glucose monitoring and insulin administration present encouraging prospects for enhancing outcomes in women with diabetes types 1 and 2. Both HDP and diabetes during pregnancy necessitate vigilant management through a combination of lifestyle modifications, pharmacological interventions, and timely obstetric care. Although certain treatments such as low-dose aspirin and metformin show efficacy in risk reduction, further research is ongoing to ensure safety for both mothers and their offspring to reduce short- and long-term adverse effects.
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The hypothalamic-pituitary-adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of 'continuous dynamic equilibration' provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. ⋯ One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24-h cortisol profiles - including during sleep - and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy.
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In this multi-professional review, we will provide the in-depth knowledge required to work in the expanding field of obesity treatment. The prevalence of obesity has doubled in adults and quadrupled in children over the last three decades. The most common treatment offered has been lifestyle treatment, which has a modest or little long-term effect. ⋯ Furthermore, we discuss common clinical challenges, such as patients with concurrent eating disorder or mental health problems, and treatment in the older adults. We also provide recommendations on how to deal with obesity in a non-stigmatizing way to diminish weight stigma during treatment. Finally, we present six microcases-obesity treatment for persons with neuropsychiatric disorders and/or intellectual disability; obesity treatment in the nonresponsive patient who has "tried everything"; and hypoglycemia, abdominal pain, and weight regain after metabolic surgery-to highlight common problems in weight-loss treatment and provide personalized treatment suggestions.
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Cushing's syndrome (CS) is a rare disorder, once exogenous causes have been excluded. However, when diagnosed, the majority of cases are adrenocorticotropic hormone (ACTH)-dependent, of which a substantial minority are due to a source outside of the pituitary, ectopic ACTH syndrome (EAS). Differentiating among pituitary-dependent CS, Cushing's disease (CD) and an ectopic source can be problematic. ⋯ BIPSS is considered to be the gold standard for differentiating CD from the EAS. Furthermore, although such differentiation may indeed be challenging, BIPSS is itself a complex investigation, especially in recent times due to the widespread withdrawal of corticotrophin-releasing hormone and its replacement by desmopressin. We review current published data on this investigation and, in the light of this and our own experience, discuss its appropriate use in diagnostic algorithms.