Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.

BACKGROUND: Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. METHODS AND RESULTS: In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P=0.24) or alendronic acid (34 [-62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P=0.75) or alendronic acid (116 [26-498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups. CONCLUSIONS: Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. REGISTRATION: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Quantitative Computed Tomography Angiography for the Evaluation of Valvular Fibrocalcific Volume in Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods. OBJECTIVES: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression. METHODS: In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort. RESULTS: Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001). CONCLUSIONS: The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients.

Systematic hand-held echocardiography in patients hospitalised with acute coronary syndrome.

AIMS: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy and time-efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting. METHODS AND RESULTS: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiography with agreement between key imaging parameters assessed using kappa statistics. The immediate clinical impact of hand-held echocardiography in this population was systematically evaluated.Overall, 262 patients (65±12 years, 71% male) participated. Agreement between hand-held and transthoracic echocardiography was good-to-excellent (kappa 0.60-1.00) with hand-held echocardiography having an overall negative predictive value of 95%. Hand-held echocardiography was performed rapidly (7.7±1.6 min) and completed a median of 5 [interquartile range 3-20] hours earlier than transthoracic echocardiography. Systematic hand-held echocardiography in all patients with acute coronary syndrome identified an important cardiac abnormality in 50% and the clinical management plan was changed by echocardiography in 42%. In 85% of cases, hand-held echocardiography was sufficient for patient decision-making and transthoracic echocardiography was no longer deemed necessary. CONCLUSIONS: In patients with acute coronary syndrome, hand-held echocardiography provides comparable results to transthoracic echocardiography, can be more rapidly applied and gives sufficient imaging information for decision-making in the vast majority of patients. Systematic echocardiography has clinical impact in half of patients, supporting the clinical utility of echocardiography in this population, and providing an evidence-base for current guidelines.

Massive continuous irrigation (MCI) and endoscopic debridement as an alternative treatment strategy for refractory abscess-fistula complexes.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of massive continuous irrigation (MCI) and endoscopic debridement for the treatment of refractory abscess-fistula complexes. METHODS: This was a retrospective single-center observational study involving 12 patients with refractory abscess-fistula complexes. All patients had experienced long-term treatment failure or had failed multiple treatment modalities. We used over two catheters and inserted them via the gastrointestinal (GI) tract or percutaneously to form a circulation pathway to achieve MCI of normal saline, endoscopic debridement was then performed. The treatment success rate, irrigation volume and treatment duration, time to abscess-fistula complex closure, intra-treatment complications, and recurrence rate were recorded. RESULTS: The treatment success rates were 100%. The median time of previous treatment was 32 days (range 7-912 days). The mean time from the use of the novel treatment strategy to abscess-fistula complex healing was 18.8 ± 11.0 days. The mean volume of irrigation was 10 804 ± 1669 mL/24 h. The mean irrigation time was 16.5 ± 9.2 days, and a median of two irrigation tubes (range 2-5) were used. No complications occurred either during or after the procedure. During the follow-up of 23.1 ± 18.1 months, no recurrence or adverse events were noted. CONCLUSIONS: MCI and endoscopic debridement may be a feasible, safe, and effective alternative treatment for refractory abscess-fistula complexes. Large prospective studies are needed to validate our results.

Translational molecular imaging: Thrombosis imaging with positron emission tomography.

A key focus of cardiovascular medicine is the detection, treatment, and prevention of disease, with a move towards more personalized and patient-centred treatments. To achieve this goal, novel imaging approaches that allow for early and accurate detection of disease and risk stratification are needed. At present, the diagnosis, monitoring, and prognostication of thrombotic cardiovascular diseases are based on imaging techniques that measure changes in structural anatomy and biological function. Molecular imaging is emerging as a new tool for the non-invasive detection of biological processes, such as thrombosis, that can improve identification of these events above and beyond current imaging modalities. At the forefront of these evolving techniques is the use of high-sensitivity radiotracers in conjunction with positron emission tomography imaging that could revolutionise current diagnostic paradigms by improving our understanding of the role and origin of thrombosis in a range of cardiovascular diseases.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Endoscopic transgastric fenestration versus percutaneous drainage for management of (peri)pancreatic fluid collections adjacent to gastric wall (with video).

BACKGROUND: Percutaneous drainage (PCD) and endoscopic approaches have largely replaced surgical drainage as the initial approach for (peri) pancreatic fluid collections (PFC)s, while complications associated with endoscopic stent implantation are common. AIM: To introduce a novel endoscopic therapy named endoscopic transgastric fenestration (ETGF), which involves resection of tissue by endoscopic accessory between gastric and PFCs without stent implantation, and to evaluate its efficacy and safety compared with PCD for the management of PFCs adjacent to the gastric wall. METHODS: Patients diagnosed with PFCs adjacent to the gastric wall and who subsequently received ETGF or PCD were restrospectively enrolled. Indications for intervention were consistent with related guidelines. We analyzed patients baseline characteristics, technical and clinical success rate, recurrence and reintervention rate, procedure-related complications and adverse events. RESULTS: Seventy-two eligible patients were retrospectively identified (ETGF = 34, PCD = 38) from October 2017 to May 2021. Patients in the ETGF group had a significantly higher clinical success rate than those in the PCD group (97.1 vs 76.3%, P = 0.01). There were no statistically significant differences regarding recurrence, reintervention and incidence of complication between the two groups. While long-term catheter drainage was very common in the PCD group. CONCLUSION: Compared with PCD, ETGF has a higher clinical success rate in the management of PFCs adjacent to the gastric wall. ETGF is an alternative effective strategy for the treatment of PFCs adjacent to the gastric wall.

Case Report: concurrent myocardial and cerebral infarction due to aortic thrombus.

Background: Aortic mural thrombus is a rare acute aortic syndrome that can present with embolism to a distal organ. No guidelines or randomized evidence exist to guide therapy for patients with aortic mural thrombus. Cardiac and cerebral embolism is a particularly unusual presentation of aortic thrombus but has significant implications for patient management. Case summary: We present an unusual case of a young patient with simultaneous embolization of aortic thrombus to the coronary and cerebral vasculature, causing cerebral infarcts and a myocardial infarction. He presented with chest pain, slurred speech, right homonymous hemianopia, and inferior ST-elevation on electrocardiogram (ECG). Bedside echocardiography identified an inferoseptal regional wall motion abnormality. Emergent computerised tomography (CT) brain and aorta showed acute cerebral infarcts and aortic mural thrombus. He was managed medically with anticoagulation and discharged without disability after a period of rehabilitation. Discussion: This case demonstrates the value of careful clinical assessment in the setting of ST-elevation prior to transferring a patient for invasive angiography, as well as highlighting the role of echocardiography and CT imaging in the diagnosis of acute aortic syndromes. We describe the various management options for aortic mural thrombus, the role of multi-disciplinary decision-making, and our rationale for selecting a strategy of anticoagulation.

[Retracted] Functional characterization of the nitrogen permease regulator­like­2 candidate tumor suppressor gene in colorectal cancer cell lines.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the microscopic images shown in Fig. 1C on p. 3489 and the invasion assay images shown in Fig. 5 on p. 3491 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes. Moreover, unexpected similarities were identified comparing between a pair of the flow cytometric assay data panels in Fig. 4 on p. 3490, considering that these data were intended to show the results from differently performed experiments. Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 3487­3493, 2015; DOI: 10.3892/mmr.2015.3881].

LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression.

LncRNA HOTAIR play important roles in the epigenetic regulation of carcinogenesis and progression in liver cancer. Previous studies suggest that the overexpression of HOTAIR predicts poor prognosis. In this study, through transcriptome sequencing data and in vitro experiments, we found that HOTAIR were more highly expressed and there is significantly positive relationship between HOTAIR and NUAK1 in liver cancer tissues and cell lines. miR-145-5p was downregulated and showed negative correlation with HOTAIR and NUAK1. Transfect Sh-HOTAIR, LZRS-HOTAIR, miR-145 mimic, miR-145 inhibitor to change the expression of HOTAIR and miR-145-5p. The addition of HTH-01-015 inhibits the expression of NUAK1. HOTAIR knockdown, miR-145-5p upregulation and NUAK1 inhibition all repressed migration, invasion and metastasis and reversed the epithelial-to-mesenchymal transition in SNU-387 and HepG2 cells. We also showed that HOTAIR recruiting and binding PRC2 (EZH2) epigenetically represses miR-145-5p, which controls the target NUAK1, thus contributing to liver cancer cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with miR-145-5p/NUAK1 during epigenetic regulation. Our findings indicate that HOTAIR/miR-145-5p/NUAK1 axis acts as an EMT regulator and may be candidate prognostic biomarker and targets for new therapies in liver cancer.

Temporal Changes in Coronary 18F-Fluoride Plaque Uptake in Patients with Coronary Atherosclerosis.

Coronary 18F-sodium fluoride (18F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary 18F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary 18F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary 18F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary 18F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary 18F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary 18F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary 18F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary 18F-fluoride uptake is a temporally stable marker of established and progressive disease.

Transgastric versus transrectal: Which access route is the best for NOTES gallbladder-preserving gallstone therapy?

OBJECTIVES: To compare the effectiveness and safety of transgastric and transrectal pure natural orifice transluminal endoscopic surgery (NOTES) for cholecystolithotomy. METHODS: This was a single-center retrospective comparative study of consecutive patients who underwent pure NOTES for either transrectal or transgastric gallbladder-preserving cholecystolithotomy between September 2017 and April 2020. Patients with symptomatic cholelithiasis were assigned for transrectal or transgastric NOTES based on the patients' choice. Treatment success, postoperative pain, peritonitis, time to resume normal diet, and duration of hospitalization were compared. RESULTS: The technical success rate was 100%. Forty-eight patients underwent successful NOTES cholecystolithotomy via the transrectal (n = 26) or transgastric route (n = 22). One (3.8%) patient in the transrectal NOTES group experienced postoperative abdominal pain compared to 6 (27.3%) in the transgastric NOTES group (P = 0.04). Fever and bile peritonitis developed in one (3.8%) patient in the transrectal NOTES group versus 8 (36.4%) in the transgastric NOTES group (P = 0.005). A postoperative fluid diet was commenced at 6 h with the transrectal approach versus on day 3 for the transgastric NOTES group. The mean postoperative hospitalization for transrectal and transgastric NOTES groups was 4.5 days versus 7 days (P = 0.001). Three patients in the transgastric NOTES group developed postoperative gastric fistula. CONCLUSIONS: Transrectal NOTES has advantages over transgastric NOTES, including preserved spatial orientation, relatively easier removal of specimens, early food intake, shorter hospitalization, fewer postoperative complications and less pain. Multicenter clinical trials with long-term follow-up are needed to confirm the safety and efficacy of both approaches.

Multi-modality imaging in aortic stenosis: an EACVI clinical consensus document.

In this EACVI clinical scientific update, we will explore the current use of multi-modality imaging in the diagnosis, risk stratification, and follow-up of patients with aortic stenosis, with a particular focus on recent developments and future directions. Echocardiography is and will likely remain the key method of diagnosis and surveillance of aortic stenosis providing detailed assessments of valve haemodynamics and the cardiac remodelling response. Computed tomography (CT) is already widely used in the planning of transcutaneous aortic valve implantation. We anticipate its increased use as an anatomical adjudicator to clarify disease severity in patients with discordant echocardiographic measurements. CT calcium scoring is currently used for this purpose; however, contrast CT techniques are emerging that allow identification of both calcific and fibrotic valve thickening. Additionally, improved assessments of myocardial decompensation with echocardiography, cardiac magnetic resonance, and CT will become more commonplace in our routine assessment of aortic stenosis. Underpinning all of this will be widespread application of artificial intelligence. In combination, we believe this new era of multi-modality imaging in aortic stenosis will improve the diagnosis, follow-up, and timing of intervention in aortic stenosis as well as potentially accelerate the development of the novel pharmacological treatments required for this disease.

Influences of dexmedetomidine on stress responses and postoperative cognitive and coagulation functions in patients undergoing radical gastrectomy under general anesthesia.

BACKGROUND: Radical gastrectomy (RG) is commonly used in the treatment of patients with gastric cancer (GC), but this procedure may lead to stress responses, postoperative cognitive dysfunction, and blood coagulation abnormalities in patients. AIM: To investigate the influences of dexmedetomidine (DEX) on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia (GA). METHODS: One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed. Of these, 50 patients had received conventional anesthesia intervention [control group (CG)] and 52 patients had received DEX in addition to routine anesthesia intervention [observation group (OG)]. Inflammatory factor (IFs; tumor necrosis factor-α, TNF-α; interleukin-6, IL-6), stress responses (cortisol, Cor; adrenocorticotropic hormone, ACTH), cognitive function (CF; Mini-Mental State Examination, MMSE), neurological function (neuron-specific enolase, NSE; S100 calcium-binding protein B, S100B), and coagulation function (prothrombin time, PT; thromboxane B2, TXB2; fibrinogen, FIB) were compared between the two groups before surgery (T0), as well as at 6 h (T1) and 24 h (T2) after surgery. RESULTS: Compared with T0, TNF-α, IL-6, Cor, ACTH, NSE, S100B, PT, TXB2, and FIB showed a significant increase in both groups at T1 and T2, but with even lower levels in OG vs CG. Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0, but the MMSE score was notably higher in OG compared with CG. CONCLUSION: In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA, DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.