Pathophysiology, Therapeutic Targets, and Future Therapeutic Alternatives in COPD: Focus on the Importance of the Cholinergic System.

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airway limitation and changes in airway structure. It has a high global burden of mortality and morbidity. The etiology of COPD is complex, but exposure to tobacco smoke and other inhaled lung oxidants are major risk factors. Both pharmacological and non-pharmacological approaches are used to manage COPD, but there remains an urgent unmet need for drugs that can modify the course of the disease. This review focuses on the role of acetylcholine and other components of the pulmonary cholinergic system in the pathogenesis of COPD, and the inhaled pharmacological agents that target it. In addition to its role as a neurotransmitter, acetylcholine regulates diverse aspects of COPD pathogenesis including bronchoconstriction, airway remodeling, mucus secretion and inflammation. Inhaled antimuscarinic drugs are a key component of therapy for COPD, as monotherapy or in combination with inhaled ß2 agonists or corticosteroids. We review the evidence supporting the use of current anticholinergic agents in COPD and preview novel drugs targeting the cholinergic system and agents from other classes in clinical development, such as phosphodiesterase-4 inhibitors and monoclonal antibodies targeting inflammatory mediators.

Beri-Beri and Wernicke Encephalopathy in a Thirty-Year-Old Male.

A 30-year-old Turkish male was found lethargic and surrounded by vomit. At the hospital, severe hypernatremic dehydration and acute kidney failure were evident. His conscious level improved with fluid resuscitation. A differential diagnosis of altered mental status was considered. A complete clinical triad of Wernicke encephalopathy (WE), supported by MRI findings, was compatible with thiamine deficiency. Previous bariatric surgery was later confirmed. Despite no clinical signs of heart failure, a high level of NT-proBNP (N-terminal prohormone brain natriuretic peptide) and a dilated, hypokinetic myocardiopathy detected on the echocardiogram led us to assume beri-beri heart disease. High-dose intravenous thiamine, ACE (angiotensin conversing enzyme) inhibitors, beta-blockers, and physical therapy were initiated with remarkable improvement in his clinical condition.

Nocardia cyriacigeorgica and Aspergillus Co-infection in a Patient with Giant-cell Arteritis.

Immunosuppressed patients are at greater risk of unusual infections. The authors present the case of a woman with giant-cell arteritis, on oral steroids, who developed cavitating pneumonia due to co-infection with Aspergillus and Nocardia. Reports of such co-infection are rare in the literature. This case highlights the importance of considering rare pathogens in immunosuppressed patients who present with non-specific symptoms, as well as the impact of such pathogens on clinical management. Another important issue is the need for prophylaxis against Nocardia spp. in immunocompromised patients. LEARNING POINTS: In patients with vasculitis on systemic corticosteroid therapy or other immunosuppressive treatment, suspicion of uncommon infection should increase in parallel with the cumulative dose of these drugs.Obtaining an accurate diagnosis and early treatment is essential, but can be very challenging.Regular prophylactic therapy should be considered. However, more research is needed to determine whether higher doses of TMP/SMX would provide adequate coverage.

Non-Uremic Calciphylaxis: A Rare Diagnosis with Limited Therapeutic Strategies.

Calciphylaxis is a rare condition characterized by the emergence of non-healing skin ulcers secondary to arterial calcification and thrombosis, typically diagnosed in patients with end-stage kidney disease (ESKD). When it develops in patients without ESKD, it is called non-uremic calciphylaxis (NUC). The latter is an even rarer diagnosis with an uncertain pathophysiology and a high mortality rate (52%), mainly due to sepsis (50%). Cutaneous biopsy is diagnostic. Therapeutic measures recommended for NUC are limited to wound debridement, analgesia, and control of infection and risk factors. Other therapeutic options exist but with a low level of evidence. We present the case of a 78-year-old woman with NUC in her lower limbs who died of sepsis. NUC is a therapeutic challenge lacking efficient strategies. LEARNING POINTS: Calciphylaxis in the absence of end-stage kidney disease is called non-uremic calciphylaxis (NUC).This disease is a diagnostic and therapeutic challenge.As therapeutic strategies for NUC mainly derive from those for uremic calciphylaxis, more efficient therapeutic measures and evidence-based recommendations are needed.