Accuracy of lung ultrasound examinations of residual congestion performed by novice residents in patients with acute heart failure.

AIMS: The popularity of B-line-guided congestion assessment by lung ultrasound (LUS) has been increasing. However, the ability of novice residents to detect residual congestion with B-line-guided assessment by LUS after decongestion treatment is poorly understood. In this study, we investigated whether novice residents (no prior echocardiography experience) can acquire the skills for B-line-guided residual congestion assessment and whether the range of variation in assessment is acceptable in actual clinical use. METHODS AND RESULTS: The study included 30 postgraduate first-year novice residents and an expert. The residents underwent training for LUS. At the end of the training session, a set of 15 LUS videos was provided to the residents, and they were asked to estimate the number of B-lines in each video. When the residents' answers greatly differed from the correct answer, we provided feedback to raise awareness of the discrepancies. After the training session, the residents performed residual congestion assessment by LUS after decongestion treatment in patients hospitalized with acute heart failure. The residents identified residual congestion in 57% of the patients. The sensitivity and specificity to identify residual congestion by the residents were 90% and 100%, respectively. The inter-operator agreement between the residents and the expert was substantial (κ = 0.86). The Spearman rank correlation coefficient for the B-lines between the expert and each resident was very high at 0.916 (P < 0.0001). CONCLUSIONS: After a brief lecture, novice residents can achieve proficiency in quantifying B-lines on LUS and can reliably identify residual congestion on LUS.

Association between B-lines on lung ultrasound, invasive haemodynamics, and prognosis in acute heart failure patients.

AIMS: Increased left atrial pressure leads to pulmonary congestion. Although the B-lines in lung ultrasound (LUS) are useful in detecting pulmonary congestion, data regarding the association between B-lines and invasive haemodynamics are inconsistent. This study aimed to explore the correlation of the B-line count by LUS with pulmonary capillary wedge pressure (PCWP) stratified for preserved and reduced ejection fraction (EF) in acute heart failure patients. METHODS AND RESULTS: We performed a prospective observational study on 116 hospitalized patients with acute heart failure (mean age, 75.2 ± 10.3 years), who underwent right heart catheterization before discharge. LUS was performed in eight zones within 4 h of right heart catheterization and compared with PCWP separately in each EF group. Cardiac events were recorded 1 year after discharge. PCWP revealed a clear pivot point at which the B-lines began to increase in the overall cohort and each EF. Specific thresholds of the increase in B-lines were identified at 19 and 25 mmHg for preserved and reduced EF, respectively. Residual congestion at discharge was defined as the presence of ≥6 B-lines. Patients with residual congestion had a higher risk for cardiac events than those without residual congestion (hazard ratio, 12.6; 95% confidence interval, 4.71-33.7; log-rank, P < 0.0001). CONCLUSION: A clear pivot point was associated with increased B-lines count in PCWP at 19 and 25 mmHg for preserved and reduced EF, respectively. Moreover, the increased B-line count above the defined cut-off used to quantify residual congestion was associated with significantly worse outcomes.

Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer.

BACKGROUND: We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. METHODS: Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated. RESULTS: CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren's intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part. CONCLUSIONS: This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients.

A 590 kb deletion caused by non-allelic homologous recombination between two LINE-1 elements in a patient with mesomelia-synostosis syndrome.

Mesomelia-synostoses syndrome (MSS) is a rare, autosomal-dominant, syndromal osteochondrodysplasia characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations due to a non-recurrent deletion at 8q13 that always encompasses two coding-genes, SULF1 and SLCO5A1. To date, five unrelated patients have been reported worldwide, and MMS was previously proposed to not be a genomic disorder associated with deletions recurring from non-allelic homologous recombination (NAHR) in at least two analyzed cases. We conducted targeted gene panel sequencing and subsequent array-based copy number analysis in an 11-year-old undiagnosed Japanese female patient with multiple congenital anomalies that included mesomelic limb shortening and detected a novel 590 Kb deletion at 8q13 encompassing the same gene set as reported previously, resulting in the diagnosis of MSS. Breakpoint sequences of the deleted region in our case demonstrated the first LINE-1s (L1s)-mediated unequal NAHR event utilizing two distant L1 elements as homology substrates in this disease, which may represent a novel causative mechanism of the 8q13 deletion, expanding the range of mechanisms involved in the chromosomal rearrangements responsible for MSS.