Update of epidemiology, survival and initial treatment in patients with gastrointestinal stromal tumour in the USA: a retrospective study based on SEER database.

OBJECTIVES: An updated epidemiological analysis of gastrointestinal stromal tumour (GIST), the change of cancer-specific survival (CSS) and patterns of initial treatment are of interest. DESIGN: A retrospective study using data from the Surveillance, Epidemiology and End Results (SEER) database. SETTING AND PARTICIPANTS: A total of 5625 patients with GIST diagnosed between 2010 and 2019 were identified. PRIMARY OUTCOME MEASURES: Age-standardised incidence rate (ASIR) and annual prevalence rate were calculated. SEER combined stage, period CSS rate and initial treatment were summarised. All the data were calculated by SEER*Stat software. RESULTS: From 2010 to 2019, the ASIR of GIST increased from 0.79 to 1.02 per 100 000 person-years, with an increase of 2.4% annually. The increase was across age and sex subgroups. The prevalence trend was similar with the ASIR trend in each subgroup. The stage distributions were similar between different age groups, but varied among different primary tumour sites. More importantly, a stage shift from regional stage to localized stage at diagnosis was found, which may result in the improvement of CSS over years. Overall, the 5-year CSS rate of GIST was approximately 81.3%. Even for metastatic GIST, the rate exceeded 50%. Surgery was the most common treatment regimen for GIST, followed by surgery and systemic treatment. Whereas approximately 7.0% patients were undertreated, which was more pronounced among patients with distant and unknown stages. CONCLUSIONS: The findings of this study suggest an improving early detection of GIST and an improving ability of accurate staging. Though most patients are effectively treated and perform good survivals, approximate 7.0% patients may be undertreated.

The WeChat platform-based health education improves health outcomes among patients with stable coronary artery disease.

OBJECTIVE: The aim of this study was to evaluate the effect of the WeChat platform-based health education on patients with stable coronary artery disease (CAD) compared with usual care. METHODS: We conducted a randomized controlled trial that included patients with stable CAD who were admitted to the Bin Hai Wan Central Hospital of Dongguan between January 2020 and December 2020. Participants in the control group received a standard regimen of care. In the WeChat group, the patients were provided with the WeChat platform-based health education by multidisciplinary team members in addition to usual care. The coprimary outcome of the study was the blood pressure, lipid profile, fasting blood glucose, Hamilton Anxiety Scale (HAMA) scores, Hamilton Depression Scale (HAMD) scores and Seattle Angina Questionnaire (SAQ) scores at 12 months, relative to baseline levels. RESULTS: Between January 2020 and December 2020, 200 eligible CAD patients were randomly assigned to WeChat group (n = 100) or usual care group (n = 100). After 12 months, the number of participants who knew the risk factors, symptoms, diagnostic criteria, management methods and treating target of CAD was significantly larger in the WeChat group than at baseline (P < 0.05) and also larger than the post-intervention level of the control group (P < 0.05). The systolic blood pressure after intervention of the WeChat group significantly decreased compared to those of the control group (132.06 ± 8.87 mmHg vs 140.32 ± 9.42 mmHg; P < 0.05). After intervention, the triglycerides, total cholesterol, and low-density lipoprotein cholesterol of the WeChat group significantly decreased compared to those at baseline and significantly decreased than those in the control group (all P < 0.05). After the intervention, scores of HAMA and HAMD both significantly decreased in the two groups. Moreover, the decreases were more significant in the WeChat group than in the control group (5.78 ± 0.98 vs 8.54 ± 1.24; 6.27 ± 1.03 vs 8.63 ± 1.66; P < 0.05). The SAQ scores of WeChat group were significantly higher than those of the control group in all 5 dimensions at the 1-year follow-up (72.71 ± 10.83 vs 59.32 ± 9.86; 80.01 ± 11.56 vs 61.98 ± 11.02; 76.76 ± 12.64 vs 65.22 ± 10.72; 83.17 ± 13.06 vs 67.01 ± 12.86; 71.82 ± 12.78 vs 55.79 ± 11.90; all P < 0.05). CONCLUSION: This study showed the high efficacy of the WeChat platform-based health education in improving health outcomes in patients with CAD. PRACTICE IMPLICATIONS: This study highlighted the potential of social media as a helpful tool for health education among patients with CAD.

ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation.

Recent studies have shown that the phosphorylation and dephosphorylation of ULK1 and ATG13 are related to autophagy activity. Although ATG16L1 is absolutely required for autophagy induction by affecting the formation of autophagosomes, the post-translational modification of ATG16L1 remains elusive. Here, we explored the regulatory mechanism and role of ATG16L1 phosphorylation for autophagy induction in cardiomyocytes. We showed that ATG16L1 was a phosphoprotein, because phosphorylation of ATG16L1 was detected in rat cardiomyocytes during hypoxia/reoxygenation (H/R). We not only demonstrated that CSNK2 (casein kinase 2) phosphorylated ATG16L1, but also identified the highly conserved Ser139 as the critical phosphorylation residue for CSNK2. We further established that ATG16L1 associated with the ATG12-ATG5 complex in a Ser139 phosphorylation-dependent manner. In agreement with this finding, CSNK2 inhibitor disrupted the ATG12-ATG5-ATG16L1 complex. Importantly, phosphorylation of ATG16L1 on Ser139 was responsible for H/R-induced autophagy in cardiomyocytes, which protects cardiomyocytes from apoptosis. Conversely, we determined that wild-type PPP1 (protein phosphatase 1), but not the inactive mutant, associated with ATG16L1 and antagonized CSNK2-mediated phosphorylation of ATG16L1. Interestingly, one RVxF consensus site for PPP1 binding in the C-terminal tail of ATG16L1 was identified; mutation of this site disrupted its association with ATG16L1. Notably, CSNK2 also associated with PPP1, but ATG16L1 depletion impaired the interaction between CSNK2 and PPP1. Collectively, these data identify ATG16L1 as a bona fide physiological CSNK2 and PPP1 substrate, which reveals a novel molecular link from CSNK2 to activation of the autophagy-specific ATG12-ATG5-ATG16L1 complex and autophagy induction.

Identification of a novel de novo mutation associated with PRKAG2 cardiac syndrome and early onset of heart failure.

INTRODUCTION: The major structure elements of the AMP-activated protein kinase (AMPK) are α, ß, and γ sunbunits. Mutations in γ2 subunit (PRKAG2) have been associated with a cardiac syndrome including inherited ventricular preexcitation, conduction disorder and hypertrophy mimicking hypertrophic cardiomyopathy. The aim of the present study was to identify PRKAG2 syndrome among patients presenting with left ventricular hypertrophy (LVH). METHODS AND RESULTS: Nineteen unrelated subjects with unexplained LVH were clinically and genetically evaluated. Among 4 patients with bradycardia, manifestations of preexcitation were only found in a 19 year old male who also developed congestive heart failure 3 years later. Electrophysiological study of this case identified the coexistence of an AV accessory pathway and AV conduction defect. Histological analysis of his ventricular tissue isolated by biopsy confirmed excessive glycogen accumulation, prominent myofibrillar disarray and interstitial fibrosis. Direct sequencing of his DNA revealed a heterozygous mutation in PRKAG2 consisting of an A-to-G transition at nucleotide 1453 (c.1453A>G), predicting a substitution of a glutamic acid for lysine at highly-conserved residue 485 (p.Lys485Glu, K485E), which was absent in his unaffected family members and in 215 healthy controls. To assess the role of K485 in the structure and function of the protein, computational modeling calculations and conservation analyses were performed. Electrostatic calculations indicate that K485 forms a salt bridge with the conserved D248 residue in the AMPK ß subunit, which is critical for proper regulation of the enzyme, and the K485E mutant disrupts the connection. CONCLUSIONS: Our study identifies a novel de novo PRKAG2 mutation in a young, in which progression of the disease warrants close medical attention. It also underlines the importance of molecular screening of PRKAG2 gene in patients with unexplained LVH, ventricular preexcitation, conduction defect, and/or early onset of heart failure.

Incidence and clinical characteristics of postcardiac injury syndrome complicating cardiac perforation caused by radiofrequency catheter ablation for cardiac arrhythmias.

BACKGROUND: Postcardiac injury syndrome (PCIS) is a complication of a variety of cardiac injuries, of which small heart perforation is the etiology that is often unrecognized. We reported a series of patients with PCIS secondary to cardiac perforation during catheter ablation procedures. METHODS AND RESULTS: Out of 1728 radiofrequency catheter ablation procedures, 21 patients (1.2%) were complicated by echo-defined cardiac perforation not requiring surgical intervention. Among them, 6 patients (6/21, 28.6%) were diagnosed with PCIS secondary to cardiac perforation because they also developed pleural effusions (6/6, 100%) and fever (4/6, 66.7%) in addition to pericardial effusion/tamponade. Four patients with PCIS (4/6, 66.7%) and four patients without PCIS (4/15, 26.7%) underwent pericardial drainage but the drainage volume during the first 24 h was not significantly different (441.3±343.9 mL vs. 182.5±151.3 mL, P=0.248). In the 6 PCIS patients, pleural effusion was detected from 3 h to 4 days (median: 2 days) after ablation procedure, predominantly bilateral (66.7%) or left-sided if unilateral. Patients with PCIS were older (64.8±7.3 years vs. 45.9±14.8 years, P=0.0078), were more likely accompanied by hypertension (66.7% vs. 6.7%, P=0.0114) and had a prolonged hospital stay (34.2±15.8 days). CONCLUSIONS: More than 25% of patients with small cardiac perforation during catheter ablation may develop PCIS which can be masked by pericardial effusion/tamponade. This kind of PCIS is more likely associated with elder or hypertensive patients and is usually characterized by early onset of pleural effusion.