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•This protocol guides safe, efficacious case selection for intracardiac echocardiography (ICE)-guided left atrial appendage occlusion (LAAO).•ICE-guided LAAO is superior to transesophageal echocardiography (TEE)-guided with fewer procedural complications.•ICE-guided LAAO procedures are shorter and avoid general anesthesia compared with TEE.•One-year follow-up shows similar outcomes for ICE and TEE-guided LAAO. Intracardiac echocardiography (ICE) has emerged as an alternative to transesophageal echo (TEE) to guide left atrial appendage occlusion (LAAO). We established a protocol to select patients appropriate for ICE guidance. Patients who underwent LAAO with the Watchman or Watchman FLX device (Boston Scientific, Marlborough, Massachusetts) from January 2018 to March 2022 at a large United States center were included. The novel protocol prospectively selected TEE or ICE guidance beginning in January 2020; previous LAAO procedures were retrospectively included. ICE was selected for patients with uninterrupted anticoagulation and appropriate LAA anatomy, renal function, and moderate sedation tolerance. In-hospital outcomes with successful implantation without conversion to TEE guidance, no peridevice leak, and no procedural complications were compared. Composite 1-year outcome included freedom from peridevice leak, device-related thrombus, stroke, and all-cause mortality. A total of 234 patients were included; the mean age was 76.1 ± 8.3 years old, and 42.3% were female. ICE guidance was used for 63 procedures; TEE guidance was used for 171 procedures. For the composite outcome, ICE-guided LAAO was superior to TEE-guided LAAO (risk difference 0.102, 96.8% vs 86.5%, 95% confidence interval 0.003 to 0.203, p = 0.029). In comparison to the TEE-guided group, ICE-guided procedures were shorter (89.1 ± 26.3 vs 99.8 ± 30.0 min, p = 0.0087) with less general anesthesia (26.6% vs 98.8%, p <0.0001). One-year composite adverse outcomes did not differ significantly (80.7% vs 88.9%, p = 0.17). In conclusion, the protocol to select appropriate patients for ICE versus TEE guidance for LAAO is safe and effective. Larger studies are indicated to validate this approach to improve outcomes, shorten procedures, and avoid general anesthesia. [Display omitted]

Clayton County is the only county in Georgia where five state representatives can live in the same house on the same street in the same community. This at-large status suffocates individual representation and perpetuates incumbency, regardless of the ineptness of ineffectiveness of the office holder.

Be the judge of what is best for Clayton County-- districts or countywide elections for the five Clayton members of the House of Representatives in the General Assembly.

I AM A PUBLIC library trustee, but, to quote one Charles Farrar Browne, my other habits are good. Mine is the clan that is regarded by professional librarians as dwelling in the dusty past (and excessively aware of next year's budget limitations); so I will be pulling a fast switch if I accuse them of being a quarter-century behind the times.

FROM a condition of uneasiness, a lack of faith in the values of securities, a question as to the methods employed by certain financiers in railway, insurance and banking circles, there came about a commercial crisis in the business interests of this country. The allaying of this uneasiness, the reestablishment of faith in our securities...

I REFER to the letter from Mr Ted Thomas (South China Morning Post, June 27) regarding the issue of government licences.

Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell–derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and β-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling.

HAVING read Ms Sylvia Lee's clarification of the core idea behind Carlsberg's advertisement (South China Morning Post, June...

Nonsense mutations are present in 10% of patients with CF, produce a premature termination codon in CFTR mRNA causing early termination of translation, and lead to lack of CFTR function. There are no currently available animal models which contain a nonsense mutation in the endogenous Cftr locus that can be utilized to test nonsense mutation therapies. In this study, we create a CF mouse model carrying the G542X nonsense mutation in Cftr using CRISPR/Cas9 gene editing. The G542X mouse model has reduced Cftr mRNA levels, demonstrates absence of CFTR function, and displays characteristic manifestations of CF mice such as reduced growth and intestinal obstruction. Importantly, CFTR restoration is observed in G542X intestinal organoids treated with G418, an aminoglycoside with translational readthrough capabilities. The G542X mouse model provides an invaluable resource for the identification of potential therapies of CF nonsense mutations as well as the assessment of in vivo effectiveness of these potential therapies targeting nonsense mutations.