Identification of Atrial Transmural Conduction Inhomogeneity Using Unipolar Electrogram Morphology.

(1) Background: Structural remodeling plays an important role in the pathophysiology of atrial fibrillation (AF). It is likely that structural remodeling occurs transmurally, giving rise to electrical endo-epicardial asynchrony (EEA). Recent studies have suggested that areas of EEA may be suitable targets for ablation therapy of AF. We hypothesized that the degree of EEA is more pronounced in areas of transmural conduction block (T-CB) than single-sided CB (SS-CB). This study examined the degree to which SS-CB and T-CB enhance EEA and which specific unipolar potential morphology parameters are predictive for SS-CB or T-CB. (2) Methods: Simultaneous endo-epicardial mapping in the human right atrium was performed in 86 patients. Potential morphology parameters included unipolar potential voltages, low-voltage areas, potential complexity (long double and fractionated potentials: LDPs and FPs), and the duration of fractionation. (3) Results: EEA was mostly affected by the presence of T-CB areas. Lower potential voltages and more LDPs and FPs were observed in T-CB areas compared to SS-CB areas. (4) Conclusion: Areas of T-CB could be most accurately predicted by combining epicardial unipolar potential morphology parameters, including voltages, fractionation, and fractionation duration (AUC = 0.91). If transmural areas of CB indeed play a pivotal role in the pathophysiology of AF, they could theoretically be used as target sites for ablation.

Strong positive light chain immunostaining in a patient with transthyretin amyloidosis.

The two most common systemic amyloidosis types are immunoglobulin light chain (AL) and amyloid transthyretin (ATTR) amyloidosis, in which the precursor proteins responsible for amyloidosis are light chain and transthyretin, respectively. Identification of precursor proteins is paramount to determine the type of amyloidosis, given that both amyloidosis types lack specificity in clinical presentation. Congo red staining followed by immunohistochemistry or immunofluorescence using fibril protein-specific antibodies is crucial for the diagnosis of amyloidosis. Here we describe a patient who was initially diagnosed with AL amyloidosis due to strong positive kappa light chain staining results. However, the diagnosis was corrected to hereditary ATTR amyloidosis using mass spectrometry and gene sequencing, confirming the important role of mass spectrometry in identifying the amyloid precursor protein and ruling out false-positive result from immunohistochemistry.

Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis.

Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM) requires an adequate peripheral blood stem cell (PBSC) collection before processing. Granulocyte-colony stimulating factor (G-CSF) with or without cyclophosphamide (CTX) is a common regimen for PBSC mobilization; their benefits and risks are controversial. To compare the efficiency, safety, and survival outcomes between the two regimens, we conducted a meta-analysis including 18 studies with 4 prospective and 14 retrospective studies; a total of 2770 patients with MM were analyzed. The CTX plus G-CSF regimen had higher yields of total CD34+ cells (SMD = 0.39, 95% CI (0.30, 0.49)), and higher mobilization rates of the target ⩾ 2 × 106/kg (OR = 3.34, 95% CI (1.82, 6.11)) and 4 × 106/kg (OR = 2.16, 95% CI (1.69, 2.76)) cells. A favorable event-free survival (EFS) (HR = 0.73, 95% CI (0.58, 0.93), p = 0.01) and better 3-year EFS rate (OR = 1.65, 95% CI (1.1, 2.47), p = 0.02) were also reached in the patients with CTX plus G-CSF mobilization, although the risks of admission (OR = 26.49, 95% CI (7.31, 95.97)) and fever (OR = 13.66, 95% CI (6.21, 30.03)) during mobilization were increased, the treatment-related mortality was consistent (p = 0.26). The CTX plus G-CSF regimen was superior to the G-CSF-alone regimen for PBSC mobilization in patients with MM.

Screening druggable targets and predicting therapeutic drugs for COVID-19 via integrated bioinformatics analysis.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19) in China, numerous research institutions have invested in the development of anti-COVID-19 vaccines and screening for efficacious drugs to manage the virus. OBJECTIVE: To explore the potential targets and therapeutic drugs for the prevention and treatment of COVID-19 through data mining and bioinformatics. METHODS: We integrated and profoundly analyzed 10 drugs previously assessed to have promising therapeutic potential in COVID-19 management, and have been recommended for clinical trials. To explore the mechanisms by which these drugs may be involved in the treatment of COVID-19, gene-drug interactions were identified using the DGIdb database after which functional enrichment analysis, protein-protein interaction (PPI) network, and miRNA-gene network construction were performed. We adopted the DGIdb database to explore the candidate drugs for COVID-19. RESULTS: A total of 43 genes associated with the 10 potential COVID-19 drugs were identified. Function enrichment analysis revealed that these genes were mainly enriched in response to other invasions, toll-like receptor pathways, and they play positive roles in the production of cytokines such as IL-6, IL-8, and INF-ß. TNF, TLR3, TLR7, TLR9, and CXCL10 were identified as crucial genes in COVID-19. Through the DGIdb database, we predicted 87 molecules as promising druggable molecules for managing COVID-19. CONCLUSIONS: Findings from this work may provide new insights into COVID-19 mechanisms and treatments. Further, the already identified candidate drugs may improve the efficiency of pharmaceutical treatment in this rapidly evolving global situation.