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Background: Lamin A/C gene (LMNA) mutations cause myocardial fibrosis manifesting as arrhythmogenic, non-compaction, or dilated cardiomyopathies. Fibro-fatty replacement largely involves the conduction system and conduction disease commonly occurs prior to contractile dysfunction. Case summary: Two young, unrelated Caucasian males, aged 34 and 25, were referred to our centre for treatment of advanced heart failure. Both patients had a family history of heart failure and sudden cardiac death among their first-degree relatives and were diagnosed with Lamin A/C mutations, but they had not been screened prior to disease onset. Although the initial phenotypes were dilated cardiomyopathy and left ventricular non-compaction cardiomyopathy, both patients' disease progressed rapidly to include ventricular arrhythmias, severe global left ventricular hypokinesis, and dependence on outpatient milrinone to complete activities of daily living. Both patients received heart transplantation within 2 years of initial disease onset. The surgical pathology of the explanted hearts revealed characteristic findings of fibro-fatty degeneration of the conduction system, and using light microscopy, they were found to have nuclear membrane thinning, bubbling, and convolution throughout all areas sampled. Discussion: Lamin A/C-related cardiomyopathy is associated with sudden cardiac death early in the disease course, warranting early consideration of implantable cardioverter defibrillator implantation, and rapid progression to end-stage cardiomyopathy refractory to standard medical therapies, necessitating early referral to an advanced heart failure centre. We report a newly observed and recorded finding of morphologic nuclear alterations in late-stage disease using high-power light microscopy. These alterations underscore the pathophysiology of Lamin A/C-related cardiomyopathy and provide a basis for future research into disease-specific therapies.
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Recurrent cryptogenic embolic strokes pose a diagnostic challenge, often necessitating an extensive evaluation to determine the underlying cause. Cancer-related stroke is a frequently overlooked etiology, accounting for a substantial proportion of cryptogenic strokes. This case study underscores the importance of considering occult malignancies in patients with recurrent strokes of unknown origin and emphasizes the need for a comprehensive diagnostic workup to detect hidden malignancies. A 50-year-old male with a complex medical history presented with expressive aphasia and blurred vision resembling previous stroke episodes. Neurological examinations revealed right hemianopsia, paraphasia, and abnormal coordination. Neuroimaging studies showed multiple chronic infarctions, a large hemorrhagic infarction in the left posterior cerebral artery territory, and a small acute-to-subacute left parietal infarction. Due to the time of presentation and the presence of hemorrhagic transformation, the patient did not meet the criteria for intravenous tissue plasminogen activator administration. Given the recurrent nature of the strokes, an extensive evaluation was initiated to determine the underlying cause. Vascular imaging, including magnetic resonance angiography (MRA) of the head and neck and a CT angiogram, showed no significant stenosis. Vasculitis workup and cardiac evaluation yielded negative results. The blood workup was notable for elevated D-dimer levels. The involvement of multiple vascular territories and recurrent stroke despite adequate treatment and the absence of traditional risk factors for stroke raised a high clinical suspicion of occult malignancy. Further investigations led to the diagnosis of locally advanced squamous cell carcinoma (P16+), metastatic to the right neck lymph nodes (cTxN3M0). Although the primary source of cancer could not be identified, the P16+ status suggests the right tonsil or base of the tongue as the probable origin. Anticoagulation therapy was initiated, and the patient was scheduled for chemoradiation therapy. Although routine cancer investigation is not justified in ischemic strokes, the possibility of an occult malignancy should be considered in the presence of multifocal infarctions across different vascular territories with elevated D-dimer levels, particularly when traditional risk factors have been ruled out. A detailed physical exam can help localize the malignancy and early identification of occult malignancies can guide appropriate management strategies and help prevent future strokes. Further clinical trials are needed to establish optimal therapeutic approaches for preventing stroke recurrence in cancer-related strokes.
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Ketamine has emerged as a potential treatment option for pediatric patients with acute asthma exacerbation who do not respond to standard therapy. This review aims to evaluate the safety and efficacy of ketamine in this population and provide an overview of the current literature. A comprehensive search was conducted in PubMed and Google Scholar, resulting in the identification of four relevant studies. The studies demonstrated that ketamine administration led to improvements in respiratory parameters, including a decrease in clinical asthma scores (CASs) and respiratory rates, and an increase in peak expiratory flow and oxygen saturation. Ketamine infusion also showed promise in obviating the need for intubation in patients with severe wheezing due to bronchiolitis. The most common side effects observed were increased tracheobronchial secretions and hallucinations, which were manageable through discontinuation or additional medication. No significant changes in heart rate and blood pressure were reported, indicating hemodynamic stability. Long-term complications of ketamine use were minimal, with no reports of nightmares or dysphoria. In conclusion, ketamine shows potential as a bronchodilator for pediatric patients with acute asthma exacerbation, although further research is needed to fully evaluate its effectiveness and long-term effects. The use of ketamine should be considered in carefully selected cases and closely monitored for adverse events.