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Background: Amyloidosis is a protein misfolding disorder that leads to the deposition of beta-pleated sheets of a fibrillar derivative of various protein precursors. Identification of the type of precursor protein is integral in treatment decision-making. The presence of two different types of amyloid in the same patient is unusually rare, and there are no previous reports of two different types of amyloid deposition in the ligamentum flavum (LF) in the same patient. Case Description: Here, we describe two patients with spinal stenosis who underwent laminectomies and were found to have AL and ATTR amyloid deposits in the LF. Conclusion: As the spine is becoming recognized as a site for ATTRwt amyloid deposition, patients undergoing spinal decompression surgery may potentially benefit from evaluation for amyloidosis in the LF.

Cardiac amyloidosis (CA) is increasingly diagnosed due to the advancements made in diagnostics and therapeutics in the last decades, particularly in the field of transthyretin-related CA. Studies that have used bone scintigraphy for screening at-risk conditions have shown that about one out of ten patients with heart failure with preserved ejection fraction (HFpEF), aortic stenosis undergoing valve replacement, or hypertrophic cardiomyopathy (HCM) diagnosed later in life might have an underlying or concomitant CA. At the same time, the epidemiology of these conditions is also rapidly evolving. HFpEF has become the leading form of heart failure, and HFpEF patients are increasingly cared for in non-cardiology settings due to their older age and substantial burden of comorbidities. Aortic stenosis is increasingly treated percutaneously at earlier stages of the disease, determining a significant gain in survival. Hypertrophic cardiomyopathy is nowadays mostly diagnosed in middle-aged adults with near-normal life expectancy, with a greater chance of misdiagnosing CA as HCM or of an overlap between the two conditions. In all these contexts, the therapeutic and prognostic implications of diagnosing CA will have to be further investigated. Meanwhile, the diagnostic workup of patients with suspected CA should always be completed with the systematic exclusion of a plasma cell dyscrasia, the acquisition of tomographic imaging at bone scintigraphy, and the completion of genetic testing for transthyretin-related forms.

The journal of biological chemistry 298(12), 102634 (2022). doi:10.1016/j.jbc.2022.102634, Myosin B (MyoB) is a class 14 myosin expressed in all invasive stages of the malaria parasite, Plasmodium falciparum. It is not associated with the glideosome complex that drives motility and invasion of host cells. During red blood cell invasion, MyoB remains at the apical tip of the merozoite but is no longer observed once invasion is completed. MyoB is not essential for parasite survival, but when it is knocked out, merozoites are delayed in the initial stages of red blood cell invasion, giving rise to a growth defect that correlates with reduced invasion success. Therefore, further characterization is needed to understand how MyoB contributes to parasite invasion. Here, we have expressed and purified functional MyoB with the help of parasite-specific chaperones Hsp90 and Unc45, characterized its binding to actin and its known light chain MLC-B using biochemical and biophysical methods and determined its low-resolution structure in solution using small angle X-ray scattering. In addition to MLC-B, we found that four other putative regulatory light chains bind to the MyoB IQ2 motif in vitro. The purified recombinant MyoB adopted the overall shape of a myosin, exhibited actin-activated ATPase activity, and moved actin filaments in vitro. Additionally, we determined that the ADP release rate was faster than the ATP turnover number, and thus, does not appear to be rate limiting. This, together with the observed high affinity to actin and the specific localization of MyoB, may point toward a role in tethering and/or force sensing during early stages of invasion., Published by Soc., Bethesda, Md.

Amyloidosis is a clinical condition characterized by amyloid fibril deposition into different organ systems. The most common types are light chain (AL) amyloidosis and transthyretin amyloidosis (ATTR) amyloidosis. Amyloidosis involves the heart with an incidence of 1.38 to 3.69 per 100,000 person-years and a prevalence of 14.85 per 100,000 person-years between 2004 and 2018. Diagnosis of cardiac amyloidosis can be made through cardiac imaging, including cardiac magnetic resonance imaging (CMR) and 99mTc-labeled pyrophosphate (PYP) cardiac scan. However, a tissue biopsy is frequently needed to confirm the diagnosis. Herein, we report such a case of cardiac amyloidosis. The patient presented with pericardial effusion and acute kidney injury as the initial presentation. The presumptive diagnosis was ATTR amyloidosis, but the endomyocardial biopsy confirmed the diagnosis of AL amyloidosis. The patient was started on bortezomib, cyclophosphamide, and dexamethasone therapy. We aimed to highlight the different diagnostic modalities of cardiac amyloidosis and the importance of obtaining tissue biopsy to confirm the amyloidosis type before starting the treatment.

Background Light-chain cardiac amyloidosis (AL-CA) has been highly valued in developed countries, but in developing countries, the recognition and diagnosis of this condition is still limited. There are currently few reports on a large number of Chinese patients with AL-CA. The present study aimed to report real-world clinical characteristics and prognosis of AL-CA in China. Methods and results Consecutive patients with AL-CA diagnosed at the Second Xiangya Hospital of Central South University between June 2012 and September 2020 were reviewed. A total of 170 patients with AL-CA have been recruited, whose mean ages were 60.81 ± 10.46. 70.59% of the patients were male. They were from eight provinces in southern China, 55.7% were referred patients, and 37.3% had been misdiagnosed previously. 64 (37.6%) patients received chemotherapy. The median survival time for patients with AL-CA was 8.00 months, and survival time for patients who received chemotherapy was 13.00 months, which was significantly longer than that of patients with palliative treatment (13.00 vs 6.00, p = 0.004). Conclusions Although clinicians have improved their understanding of AL-CA in recent years, the prognosis of AL-CA is still poor, and the misdiagnosis rate and missed diagnosis rate are still very high in China. It is imperative to improve the recognition and early diagnosis of this condition, which may require multidisciplinary collaboration among cardiologists, hematologists and nephrologists.