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Globally, gastric cancer (GC) is an urgent health concern, necessitating an understanding of its genetic and epigenetic regulation. The tumor suppressor Setd2, H3K36me3 methyltransferase, has been associated with malignancies. The underlying signaling mechanisms and the function of Setd2 in GC aggravation are yet unclear. To figure out this question, we utilized a mouse model with c-Myc overexpression and Setd2 knockout in gastric parietal cells to conduct histological and molecular analysis. Our results demonstrated that deletion of Setd2 exacerbated gastric adenoma induced by c-Myc overexpression. Moreover, we revealed that PI3K/AKT signaling pathway contributed to the development of gastric adenoma, offering GC patients a potentially effective treatment approach.

Background: Using antimicrobials wisely is crucial for effective treatment and reducing antimicrobial resistance (AMR). As ocular infections can lead to serious consequences and ophthalmic surgery has a great impact on patients, the application of antimicrobials in ophthalmology needs to be managed in a standardized manner. Methods: A multidisciplinary team (MDT) on antimicrobial stewardship was set up by adopting comprehensive management measures and a continuous improvement model with all-staff training and empowerment, information-assisted medical prescription control, and transparent supervision. Results: After intervention, the antibiotics use density, antibiotics utilization rate and antibiotics prophylactic utilization rate for type I incision operation among inpatients decreased from 30.02%, 49.64% and 58.04% in 2018 to 8.78% (decrease by 70.77%), 18.31% (p < 0.001) and 8.93% (p < 0.001) in 2022, respectively; the microbiological submission rate related to antibiotics utilization, etiological submission rate before antibiotic therapy and before combined use of key antibiotics rose from 13.44%, 17.39% and 50.00% to 27.33% (p < 0.001), 51.3% (p < 0.001) and 100.00% (increase by 100%), respectively; the incidence of nosocomial infection and surgical site infection for type I incision operation both reduced to zero, while the use of hand hygiene products markedly increased. For pathogen detection, a total of 489 pathogens were isolated from 2018 to 2022, of which 69.30% were Gram-positive bacteria, 26.02% were Gram-negative bacteria, and 4.68% were fungi. Ocular secretion was the main detection site (89.31%). Antibiotic resistance analysis results indicated that Staphylococci maintained complete sensitivity to linezolid, vancomycin, and teicoplanin. Streptococcus pneumoniae maintained complete sensitivity to vancomycin, benzathine, levofloxacin, and moxifloxacin, with resistance to penicillin G and ceftriaxone down to zero. Conclusion: Multidisciplinary team and information-assisted transparent supervision have displayed obvious effects in promoting the standardized application of antimicrobials in ophthalmology, via distinctly improving indicators relevant to antimicrobial application and nosocomial infection. Our work may provide guidance for improving the medical quality and curbing the AMR. [ABSTRACT FROM AUTHOR]

Background and Aims HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. Methods A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. Results Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1–3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). Conclusions Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure. [ABSTRACT FROM AUTHOR]

Aims: We assessed the incidence, predictors and clinical correlates of de‐novo aortic regurgitation (AR), which physiologically reduces left ventricular assist device (LVAD) effectiveness due to recirculation syndrome, in the MOMENTUM 3 trial portfolio of the fully magnetically levitated HeartMate 3 (HM3) pump using the randomized pivotal trial (PT) and post‐trial continued access protocol (CAP). Methods and results: De‐novo aortic regurgitation incidence at 2 years was analysed in the randomized PT and validated in the first 1000 implanted patients of the CAP. Patients with concomitant/prior aortic valve surgery or without baseline or post‐implant echocardiograms were excluded from this analysis. AR severity was assessed qualitatively by site‐adjudicated echocardiograms (significant AR was defined as moderate or severe grade on echocardiogram). Of 1028 patients enrolled in the PT, 918 were eligible for inclusion in this analysis (HM3, n = 465; HMII, n = 453). At 2 years of LVAD support, freedom from significant AR was greater in the HM3 (92%) than HMII (82%) (hazard ratio 0.45, 95% confidence interval 0.27–0.75, p < 0.01). Of 907 HM3 patients analysed from the first 1000 implanted CAP patients, the rate of freedom from significant AR was 90%, consistent with the PT (p = 0.3). In the combined HM3 group (n = 1372), multivariable Cox modelling identified increasing age and female sex as significant predictors. Survival free of urgent transplant or AR corrective procedure was similar between HM3 patients with and without significant de‐novo AR. Conclusions: The development of moderate or severe grade de‐novo AR is reduced with the fully magnetically levitated HM3 LVAD compared to the axial‐flow HMII pump. The occurrence of significant de‐novo AR with the HM3 pump is not associated with a worse outcome at 2 years of follow‐up. [ABSTRACT FROM AUTHOR]

Aims: Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF). Methods and results: The MEMS‐HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS‐HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non‐users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan‐treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non‐loop diuretics (P = 0.21). Conclusions: In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes. [ABSTRACT FROM AUTHOR]

The therapeutic potential of Annexin A1, an important member of the Annexin superfamily, has become evident in results of experiments with multiple human systems and animal models. The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system. In this review, we initially describe the expression sites of Annexin A1, then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches; and, finally, we discuss the neuroregenerative potential qualities of Annexin A1. The eye and the nervous system are anatomically and functionally connected, but the association between visual system pathogenesis, especially in the retina, and Annexin A1 alterations has not been well summarized. Therefore, we explain the beneficial effects of Annexin A1 for ocular diseases, especially for retinal diseases and glaucoma on the basis of published findings, and we explore present and future delivery strategies for Annexin A1 to the retina.

OBJECTIVE. The purpose of this study was to compare the cancer detection rates (CDRs), tumor types, and characteristics between screening digital breast tomosynthesis (DBT) and screening full-field digital mammography (FFDM) in a matched patient population in a large academic breast imaging practice with mixed DBT and FFDM technology. MATERIALS AND METHODS. In this retrospective study, we reviewed consecutive screening FFDM and DBT examinations performed between October 2012 and September 2014. To control for nonrandomized selection of FFDM versus DBT examinations, we applied propensity score matching on the basis of patient age, imaging site, and prior imaging findings. An institutional breast cancer registry identified cancer diagnoses. CDR and tumor type, grade, receptor, nodal status, and size were compared between matched FFDM and DBT groups. RESULTS. Sixty-one cancers were detected in the matched screening cohort of DBT ( n = 9817) and FFDM ( n = 14,180) examinations. CDR was higher with DBT than with FFDM for invasive cancers (2.8 vs 1.3, p = 0.01), minimal cancers (2.4 vs 1.2, p = 0.03), estrogen receptor-positive invasive cancers (2.6 vs 1.1, p = 0.01), and node-negative invasive cancers (2.3 vs 1.1, p = 0.02.), respectively. The ratio of screen-detected invasive cancers to ductal carcinoma in situ on DBT (3.0) was not significantly different from that on FFDM (2.6) ( p = 0.79). CONCLUSION. DBT results in an overall increase in CDR irrespective of the tumor type, size, or grade of cancer.

OBJECTIVE. The purpose of this study was to evaluate the impact of an information technology-enabled quality improvement initiative on timeliness of patient contact and scheduling of screening mammography recall. MATERIALS AND METHODS. The study was conducted in a screening practice (two ambulatory centers, A and B; two hospitals, C and D) that uses offline batch results (A, B, C) and same-day results (D) with on-site (A, C, D) or off-site (B) coordinators scheduling recalls. Before the intervention, radiologists at sites A, B, and C conveyed recalls via paper lists to coordinators after batch interpretation. At site D, coordinators received recall lists several times a day. In March 2017 an electronic alert system was implemented to notify coordinators of recall at report signing with required closed-loop acknowledgment once recall was scheduled. Mean time (hours, excluding weekends) to schedule diagnostic evaluation was compared for 4-month periods before and after intervention by two-tailed t test and statistical process control analyses. RESULTS. Recall rates were 9.5% (1356/14,315) before and 8.9% (1432/16,034) after the intervention ( p = 0.10). Mean time to schedule screening decreased after the intervention as follows: site A from 86 to 65 hours (-24.4%, p = 0.01); site B, 116 to 70 hours (-39.7%, p < 0.0001); site C, 98 to 65 hours (-33.7%, p = 0.002); and site D, 49 to 42 hours (-14.3%, p = 0.21). Statistical process control analysis showed significant sustained improvements at sites A, B, and C in mean time to patient contact and scheduling of diagnostic evaluation. CONCLUSION. An information technology-enabled quality improvement initiative to notify coordinators of screening recalls in real time with required patient contact and scheduling acknowledgment reduced time to diagnostic scheduling in a multisite practice. The greatest impact was found at the site with off-site coordinators, the least at the site performing same-day interpretation.

OBJECTIVE. The objective of our study was to improve adherence to American College of Radiology (ACR) white paper follow-up imaging recommendations for incidental adnexal lesions seen on pelvic CT (herein referred to as "adherence rate to recommendations"). MATERIALS AND METHODS. This quality improvement project was conducted at a large academic teaching hospital. The baseline adherence rate to recommendations was assessed by screening all pelvic CT reports for the period from October 22, 2016, through December 22, 2016, for incidental adnexal findings, followed by manual review. Forty abdominal and cancer imaging radiologists were surveyed to understand the barriers to adoption of the recommendations. Interventions to address the most common identified barriers were implemented on December 23, 2016. The postintervention adherence rate was assessed from December 23, 2016, through February 15, 2017, by again screening CT pelvis reports for incidental adnexal lesions followed by manual review. The change in pre- and postintervention adherence rates was assessed using the Fisher exact test and statistical process control (SPC) p-chart with 3-sigma control limits. RESULTS. The adherence rate to recommendations at baseline was 67% (121/181). Of the 28 of 40 (70%) radiologists who completed the survey, only 29% (8/28) often or consistently used the recommendations. Not remembering the details of the recommendations or not having time to look them up accounted for 83.3% of the barriers cited by radiologists. Interventions consisted of radiologist education and creation of an easily accessible clinical decision support tool incorporated into radiology reporting workflow. The adherence rate to recommendations after the intervention increased to 87% (129/148; p < 0.0001), as also shown by the SPC chart. CONCLUSION. The rate of adherence to follow-up imaging recommendations significantly increased after radiologist education and incorporation of recommendations into the radiologist workflow.