The widespread use of video-electroencephalogram monitoring has dramatically increased our recognition of the high prevalence and diversity of nonepileptic seizures. Nonepileptic seizures stand squarely in the interface between psychiatry and neurology, an area that has been both claimed and denied by both sides. Collaborative exploration of this border zone has provided new insights into a disorder that may be as ancient as epilepsy.

Nonepileptic seizures.

Neurologic Clinics

This review article series on water and electrolyte disorders is based on the 'Electrolyte Winter Seminar' held annually for young nephrologists in Japan. The seminar features dynamic case-based discussions, some of which are included as self-assessment questions in this series. The second article in this series focuses on treatment of hyponatremia, a common water and electrolyte disorder frequently encountered in clinical practice. Hyponatremia presents diagnostic challenges due to its various etiologies and the presence of co-morbidities that affect water and electrolyte homeostasis. Furthermore, limited evidence, including a lack of robust randomized controlled trials, complicates treatment decisions and increases the risk of poor outcomes from inappropriate management of both acute and chronic hyponatremia. This review provides a comprehensive overview of treatment of hyponatremia for better comprehension and improved clinical practice.

Treatment of hyponatremia: comprehension and best clinical practice.

Clinical and Experimental Nephrology

Fever is a classic reason for hospital visits, sometimes requiring admission. Its etiologies are numerous, ranging from simple and relatively common conditions to rare and complex pathologies, for which the differential diagnosis can present a true challenge for internists. A 78-year-old healthy female is referred to the emergency department due to marked fatigue for the past four months, with no other symptoms. Physical examination revealed fever, significant lower limb edema, and low blood pressure. Laboratory results revealed anemia and thrombocytopenia, associated with high ferritin and lactate dehydrogenase levels (1924 U/L and 1519 U/L, respectively) and mild hyponatremia (133 mEq/L). A thoracic-abdominal-pelvic CT scan showed only a splenomegaly of 17 cm without other significant findings. No microorganisms were found in multiple cultural samples, and fever persisted despite two courses of antibiotics. Viral serologies and zoonosis panel were negative. A bone marrow study was conducted to help explain the cytopenias, which revealed hemophagocytic cells, confirming the diagnosis of hemophagocytic syndrome. She started with systemic corticosteroid therapy, which improved her symptoms, and a few days later, it was confirmed a diffuse large B-cell lymphoma was the etiology. Because of its mostly unspecific manifestations, hemophagocytic syndrome requires a high degree of suspicion for timely diagnosis and treatment.

Fever of Unknown Origin: A Rare Diagnosis Requiring High Suspicion.

Curēus

Recent progress has notably improved outcomes for patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), namely granulomatosis with polyangiitis and microscopic polyangiitis. Since 2021, several international scientific societies have recommended rituximab (RTX) as the preferred primary treatment for maintaining remission in AAV patients. Decisions regarding retreatment with RTX are based on individual patient risk factors for disease flare-ups and the potential consequences of such flares. In reviewing available evidence and reporting our experiences at G. Bosco Hub Hospital in Turin, Italy, we explore various trials focusing on the maintenance therapy in AAV and discuss areas of unmet need.

How We Treat ANCA-Associated Vasculitis: A Focus on the Maintenance Therapy.

Journal of Clinical Medicine

Allergic rhinitis (AR) is a common disorder that is strongly linked to asthma and conjunctivitis. Classic symptoms include nasal congestion, nasal itch, rhinorrhea and sneezing. A thorough history, physical examination and assessment of allergen sensitization are important for establishing the diagnosis of AR. Intranasal corticosteroids and second-generation antihistamines are the mainstay of treatment. Allergen immunotherapy is an effective immune-modulating treatment for use in addition to or as an alternative to pharmacologic therapy. This article provides an overview on the pathophysiology, diagnosis, and appropriate management of AR.

Allergic rhinitis.

Allergy, Asthma, and Clinical Immunology

Insomnia is a common and challenging complaint in older adults (&gt; 65 years) because of age-related alterations in sleep physiology. Cognitive behavioral therapy for insomnia is the gold standard for treatment of insomnia in young as well as older patients. Both clinicians and patients often prefer the simplicity of medication, but risks associated with some hypnotics increase with age. Pharmacologic options for older adults include low-dose doxepin, melatonin, ramelteon, and the dual orexin receptor antagonists. A well-informed clinician can help patients navigate the risks and benefits of both pharmacologic and behavioral options.

Insomnia in older adults: A review of treatment options.

Cleveland Clinic Journal of Medicine

Aldosterone is a key regulator of fluid and electrolyte balance in the body. It is often dysregulated in heart failure (HF) and is a key driver of cardiac remodelling and worse clinical outcomes. Potassium regulation is essential for normal cardiac, gastrointestinal and neuromuscular function. Serum potassium fluctuations are largely determined by aldosterone, the final step of the renin-angiotensin-aldosterone system. Dyskalaemia (i.e. hypokalaemia and hyperkalaemia) is prevalent in HF because of the disease itself, its therapies and related comorbidities such as chronic kidney disease. Prognostic implications of abnormal serum potassium follow a U-shaped curve, where both hypokalaemia and hyperkalaemia are associated with adverse outcomes. Hypokalaemia is associated with increased mortality, starting from potassium &lt;4.0 mmol/l but especially at potassium &lt;3.5 mmol/l. Hyperkalaemia, along with increasing arrhythmia risk, limits the use of lifesaving renin-angiotensin- aldosterone system inhibitors, which may have long-term survival implications. The advent of novel potassium binders aims to manage chronic hyperkalaemia and may allow for uptitration and optimal dosing of guideline-recommended therapy. This review discusses the impacts of dyskalaemia in HF, along with management strategies, including the relevance of potassium binder use in optimising HF treatment. Current and potential future aldosterone-modulating therapies, such as non-steroidal mineralocorticoid receptor antagonists and aldosterone synthase inhibitors, are also discussed.

Aldosterone and Potassium in Heart Failure: Overcoming This Major Impediment in Clinical Practice.

Cardiac Failure Review

Sepsis often leads to vasoplegia and a hyperdynamic cardiac state, with treatment focused on restoring vascular tone. However, sepsis can also cause reversible myocardial dysfunction, particularly in the elderly with pre-existing heart conditions. The Surviving Sepsis Campaign Guidelines recommend using dobutamine with norepinephrine or epinephrine alone for patients with septic shock with cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and stable blood pressure. However, the definition of cardiac dysfunction and hypoperfusion in these guidelines remains controversial, leading to varied clinical interpretations. Cardiac dysfunction with persistent hypoperfusion despite restoring adequate preload and afterload is often considered a cardiogenic shock. Therefore, sepsis complicated by new-onset myocardial dysfunction or worsening of underlying myocardial dysfunction due to sepsis-induced cardiomyopathy, resulting in cardiogenic shock, can be defined as "Sepsis-induced cardiogenic shock (SICS)". SICS is known to be associated with significantly higher mortality. A history of cardiac dysfunction is a strong predictor of SICS, highlighting the need for precise diagnosis and management given the aging population and rising cardiovascular disease prevalence. Therefore, SICS might benefit from early invasive hemodynamic monitoring with a pulmonary artery catheter (PAC), unlike those with septic shock alone. While routine PAC monitoring for all septic patients is impractical, echocardiography could be a useful screening tool for high-risk individuals. If echocardiography indicates cardiogenic shock, PAC might be warranted for continuous monitoring. The role of inotropes in SICS remains uncertain. Mechanical circulatory support (MCS) might be considered for severe cases, as high-dose vasopressors and inotropes are associated with worse outcomes. Correct patient selection is the key to improving outcomes with MCS. Engaging a cardiogenic shock team for a multidisciplinary approach can be beneficial. In summary, addressing the evidence gaps in SICS diagnosis and management is crucial. Echocardiography for screening, advanced monitoring with PAC, and careful patient selection for MCS are important for optimal patient care.

Sepsis-induced cardiogenic shock: controversies and evidence gaps in diagnosis and management.

Journal of Intensive Care

Heart failure (HF) is a major contributor to hospitalisations and accounts for 7% of cardiovascular-related deaths, with patients who have chronic kidney disease and type 2 diabetes at heightened risk. Existing treatment guidelines inadequately address these comorbidities. Steroidal mineralocorticoid receptor antagonists (MRAs) are commonly used in HF with reduced ejection fraction but pose risks, such as hyperkalaemia and acute kidney injury. Finerenone, a non-steroidal MRA, offers a safer alternative, with higher selectivity, reduced electrolyte disturbances and beneficial effects on heart and kidney tissues. Preclinical studies show anti-inflammatory and anti-fibrotic effects, while phase III trials (ARTS and ARTS-HF) demonstrated fewer hyperkalaemia incidents compared with spironolactone. In phase III trials (FIDELIO-DKD and FIGARO-DKD), finerenone reduced HF hospitalisations by 22% in patients with chronic kidney disease and type 2 diabetes. The FINEARTS-HF trial found that finerenone significantly reduced the risk of worsening HF events or CV death in patients with HF with mildly reduced or preserved ejection fraction. Its combination with therapies, such as sodium-glucose cotransporter 2 inhibitors, shows promise and ongoing trials, such as REDEFINE-HF, FINALITY-HF and CONFIRMATION-HF, are investigating its efficacy in other HF phenotypes. These studies will further establish the role of finerenone in managing cardio-renal-metabolic diseases.

Finerenone: Will It Be a Game-changer?

Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.

The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.

Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL-IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL-IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high-risk stages has improved.

Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment-free interval exceeds 3&#x2009;years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen.

Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed-duration therapies have gained territory in the management of CLL, as they are cost-effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patients who are double-refractory to both BTK and BCL2 inhibitors. These patients need to be treated within experimental protocols using novel drugs.

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