Long-term outcome in patients with chronic atrial fibrillation after successful internal cardioversion

Internal cardioversion is safe and effective in restoring sinus rhythm, even in patients with persistent AF of prolonged duration. Up to 40% to 50% of patients with AF lasting >1 year but <3 years could be maintained in sinus rhythm using a class III antiarrhythmic drug after successful internal cardioversion, and amiodarone appears to be more effective than sotalol in this patient population.     

Clonal evolution of high‐grade serous ovarian carcinoma from primary to recurrent disease

High‐grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum‐ and taxane‐based chemotherapy, the majority of patients experience recurrence of treatment‐resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.     

The Effect of Moving Point of Contact Stimulation on Chondrocyte Gene Expression and Localization in Tissue Engineered Constructs

Tissue engineering is a promising approach for articular cartilage repair. However, using current technologies, the developed engineered constructs generally do not possess an organized superficial layer, which contributes to the tissue’s durability and unique mechanical properties. In this study, we investigated the efficacy of applying a moving point of contract-type stimulation (MPS) to stimulate the production of a superficial-like layer in the engineered constructs. MPS was applied to chondrocyte-agarose hydrogels at a frequency of 0.5, 1 or 2 Hz, under a constant compressive load of 10 mN for durations between 5 and 60 min over 3 consecutive days. Expression and localization of superficial zone constituents was conducted by qRT-PCR and in situ hybridization. Finite element modeling was also constructed to gain insight into the relationship between the applied stimulus and superficial zone constituent expression. Gene expression of superficial zone markers were affected in a frequency dependent manner with a physiologic frequency of 1 Hz producing maximal expression of PRG4, biglycan, decorin and collagen II. In situ hybridization revealed that localization of these markers predominantly occurred at 500–1000 μm below the construct surface which correlated to sub-surface strains between 10 and 25% as determined by finite element modeling. These results indicate that while mechanical stimuli can be used to enhance the expression of superficial zone constituents in engineered cartilage constructs, the resultant subsurface loading is a critical factor for localizing expression. Future studies will investigate altering the applied stimulus to further localize superficial zone constituent expression at the construct surface.