Kinin-kallikrein system: New perspectives in heart failure.

Heart failure (HF) is a pervasive clinical challenge characterized by compromised cardiac function and reduced quality of life. The kinin-kallikrein system (KSS), a multifaceted peptide cascade, has garnered substantial attention due to its potential role in HF. Through activation of B1 and/or B2 receptors and downstream signaling, kinins modulate various physiological processes, including inflammation, coagulation, pain, blood pressure control, and vascular permeability. Notably, aberrations in KKS components have been linked to HF risk. The elevation of vasodilatory bradykinin (BK) due to kallikrein activity reduces preload and afterload, while concurrently fostering sodium reabsorption inhibition. However, kallikrein's conversion of prorenin to renin leads to angiotensinsII upregulation, resulting in vasoconstriction and fluid retention, alongside increased immune cell activity that fuels inflammation and cardiac remodeling. Importantly, prolonged KKS activation resulting from volume overload and tissue stretch contributes to cardiac collagen loss. The conventional renin-angiotensin-aldosterone system (RAAS) inhibitors used in HF management may inadvertently intensify KKS activity, exacerbating collagen depletion and cardiac remodeling. It is crucial to balance the KKS's role in acute cardiac damage, which may temporarily enhance function and metabolic parameters against its detrimental long-term effects. Thus, KKS blockade emerges as a promising strategy to impede HF progression. By attenuating the link between immune system function and tissue damage, KKS inhibition can potentially reduce cardiac remodeling and alleviate HF symptoms. However, the nuanced roles of BK in various acute conditions necessitate further investigation into the sustained benefits of kallikrein inhibitors in patients with chronic HF.

New Daily Persistent Headache (NDPH): Unraveling the Complexities of Diagnosis, Pathophysiology, and Treatment.

PURPOSE OF REVIEW: The current article aims to provide an overview of new daily persistent headache (NDPH), with a particular emphasis on its pathophysiology, evaluation, and current treatment options. RECENT FINDINGS: NDPH is an uncommon and heterogeneous condition associated with various comorbidities and is of great significance due to its prolonged duration and high severity. Variable causes and clinical aspects of NDPH may reflect differences in its underlying pathophysiological mechanisms, including genetics, environmental triggers, neuroinflammation, and brain changes. When assessing a patient with NDPH, potential triggers, past medical history, and differential diagnosis should be carefully considered. Non-pharmacological interventions aimed to improve diet, sleep patterns, and reduce consumption of caffeine and alcohol are recommended for all patients. Nerve blockade and nerve stimulation seem to be more efficacious in children than adults. Antiviral medications and neuroinflammation-targeting treatments may be helpful, particularly, when an infectious disease or severe inflammation is suspected. NDPH patients with concurrent affective disorders may benefit from treatment with serotonin reuptake inhibitors, serotonin/norepinephrine reuptake inhibitors, or benzodiazepines. Cerebrospinal-fluid-lowering medications may be useful for headaches started with a thunderclap or a Valsalva maneuver. Possible treatments for refractory NDPH include intravenous ketamine or lidocaine, onabotulinumtoxinA, and calcitonin gene-related peptide antibodies. Considering the variety of NDPH, it is critical to properly screen patients for correct diagnosis. Proper identification of potential mimics may enable precise therapy opportunities, yet there is no gold standard treatment for NDPH. Further well-designed studies are needed to elucidate the underlying mechanisms and develop effective treatment strategies for NDPH.