The aim of this study was to describe the effects of sodium‐glucose co‐transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, CENTRAL, ...EMBASE and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to May 20, 2017. A total of 62 studies, comprising 34 941 patients, were included. Any of the SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total weighted mean difference WMD −37.73 μmol/L, 95% CI −40.51, −34.95). Treatment with empagliflozin resulted in a superior reduction in SUA (WMD −45.83 μmol/L, 95% CI −53.03, −38.63). The effect persisted during long‐term treatment. Dapagliflozin decreased SUA in a dose‐dependent manner (from 5 to 50 mg, P = .014). In subgroup analyses, greater reductions could be observed during the course of early diabetes and the SUA‐lowering effect was abolished in patients with chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m2). The effect of SGLT2 inhibitors on SUA reduction suggests that this class of drugs might be beneficial for diabetic patients with hyperuricaemia.
Background
This study aimed to retrospectively evaluate the feasibility of total-body
18
F-FDG PET/CT ultrafast acquisition combined with a deep learning (DL) image filter in the diagnosis of ...colorectal cancers (CRCs).
Methods
The clinical and preoperative imaging data of patients with CRCs were collected. All patients underwent a 300-s list-mode total-body
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F-FDG PET/CT scan. The dataset was divided into groups with acquisition durations of 10, 20, 30, 60, and 120 s. PET images were reconstructed using ordered subset expectation maximisation, and post-processing filters, including a Gaussian smoothing filter with 3 mm full width at half maximum (3 mm FWHM) and a DL image filter. The effects of the Gaussian and DL image filters on image quality, detection rate, and uptake value of primary and liver metastases of CRCs at different acquisition durations were compared using a 5-point Likert scale and semi-quantitative analysis, with the 300-s image with a Gaussian filter as the standard.
Results
All 34 recruited patients with CRCs had single colorectal lesions, and the diagnosis was verified pathologically. Of the total patients, 11 had liver metastases, and 113 liver metastases were detected. The 10-s dataset could not be evaluated due to high noise, regardless of whether it was filtered by Gaussian or DL image filters. The signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in the images acquired for 10, 20, 30, and 60 s with a Gaussian filter was lower than that of the 300-s images (
P
< 0.01). The DL filter significantly improved the SNR and visual image quality score compared to the Gaussian filter (
P
< 0.01). There was no statistical difference in the SNR of the liver and mediastinal blood pool, SUVmax and TBR of CRCs and liver metastases, and the number of detectable liver metastases between the 20- and 30-s DL image filter and 300-s images with the Gaussian filter (
P
> 0.05).
Conclusions
The DL filter can significantly improve the image quality of total-body
18
F-FDG PET/CT ultrafast acquisition. Deep learning-based image filtering methods can significantly reduce the noise of ultrafast acquisition, making them suitable for clinical diagnosis possible.
Purpose
Primary thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of MALT lymphoma. We aim to investigate the clinicopathologic features,
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...F-FDG PET/CT findings and outcomes for patients with primary thymic MALT lymphoma; to explore the correlation between metabolic parameters and immunohistochemical phenotypes.
Methods
A retrospective single-center study enrolled 12 patients with primary thymic MALT lymphoma between 2010 and 2021. Nineteen
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F-FDG PET/CT scans were performed, and clinicopathologic and immunohistochemical characteristics, PET/CT imaging features, and outcomes were analyzed.
Results
The male-to-female ratio was 1. The median age at diagnosis was 40 (range 31–68). The long diameter of the lesions ranged from 3.5 to 15.7. Histopathological examinations revealed that the normal thymic lobular architecture was effaced by a diffuse lymphoid infiltrate, but residual Hassall corpuscles could still be identified, mostly with CD20+, PAX5+, CD3-, CD23-, CD10-, BCL-6-, cyclin D1-, EBER- and low Ki-67. The gene rearrangement indicated that the IGH gene but not TCR gene was found in 7 patients. Six initial PET/CT scans showed a mean SUVmax of 6.8 (range, 3.1–12.4), a mean MTV = 40.0 (range, 6.7–81.4), and a mean TLG = 144.3 (range, 19.7–286.4). During the follow-up period, there was no death except for the patient with DLBCL who died 59 months after diagnosis of primary thymic MALT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.355,
P
> 0.05).
Conclusion
Primary thymic MALT lymphoma should be considered in patients with multilocular cystic lesions with different degrees of
18
F-FDG uptake in the anterior mediastinum. The results of this study showed no correlation between SUVmax and Ki-67 index.
To investigate the prognostic significance of liver tumor markers, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score; neutrophil-to-lymphocyte ratio (NLR); and platelet-to-lymphocyte ...ratio (PLR), for predicting the specific site of recurrence or metastasis after surgery in patients with intrahepatic cholangiocarcinoma (ICC).
In total, 162 patients with pathologically proven ICC who underwent curative surgery at Sun Yat-sen University Cancer Center between April 2016 and April 2020 were analyzed. Clinicopathological characteristics were collected retrospectively. The Kaplan-Meier method was used to analyze the overall survival (OS) and recurrence-free survival (RFS). Significant clinical factors were examined by univariate analysis and multivariate analysis and analyzed by receiver operating characteristic (ROC) curve analysis.
The cutoff values for the HALP score, NLR, and PLR were determined to be 43.63, 3.73, and 76.51, respectively, using the surv_cutpoint function of survminer using RFS as the target variable. In multivariate analysis, vascular invasion, pathology nerve tract invasion, and carbohydrate antigen 19-9 (CA19-9) levels were independent prognostic factors of OS, whereas the tumor number, pathology microvascular invasion, pathology differentiation, CA19-9 levels, and NLR were independent prognostic factors of RFS. For the whole recurrence analysis, the carcinoembryonic antigen (CEA) index exhibited the largest ROC curve area of all (AUC = 0.590), and the alpha-fetoprotein (AFP) index exhibited the smallest ROC curve area (AUC = 0.530). The HALP score exhibited the largest ROC curve area of all in predicting intrahepatic recurrence (AUC = 0.588), the NLR showed the best predictive value in predicting lymph node metastasis (AUC = 0.703), and the AUC of the CA19-9 index was the largest of all variables in predicting distant metastasis (AUC = 0.619).
Our study showed that CA19-9, CEA, HALP score, and NLR are easily accessible, reliable, cost-effective indexes for predicting the specific site of recurrence or metastasis after surgery in ICC patients. Patients with high HALP scores and NLR have a higher risk of intrahepatic and lymph node metastasis recurrence.
Objectives
This study aims to decrease the scan time and enhance image quality in pediatric total-body PET imaging by utilizing multimodal artificial intelligence techniques.
Methods
A total of 270 ...pediatric patients who underwent total-body PET/CT scans with a uEXPLORER at the Sun Yat-sen University Cancer Center were retrospectively enrolled.
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F-fluorodeoxyglucose (
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F-FDG) was administered at a dose of 3.7 MBq/kg with an acquisition time of 600 s. Short-term scan PET images (acquired within 6, 15, 30, 60 and 150 s) were obtained by truncating the list-mode data. A three-dimensional (3D) neural network was developed with a residual network as the basic structure, fusing low-dose CT images as prior information, which were fed to the network at different scales. The short-term PET images and low-dose CT images were processed by the multimodal 3D network to generate full-length, high-dose PET images. The nonlocal means method and the same 3D network without the fused CT information were used as reference methods. The performance of the network model was evaluated by quantitative and qualitative analyses.
Results
Multimodal artificial intelligence techniques can significantly improve PET image quality. When fused with prior CT information, the anatomical information of the images was enhanced, and 60 s of scan data produced images of quality comparable to that of the full-time data.
Conclusion
Multimodal artificial intelligence techniques can effectively improve the quality of pediatric total-body PET/CT images acquired using ultrashort scan times. This has the potential to decrease the use of sedation, enhance guardian confidence, and reduce the probability of motion artifacts.
Pheochromocytoma and paraganglioma (PHEO-PGL) and cyanotic congenital heart disease (CCHD) are both rare diseases. We reported a 30-year-old patient with a right adrenal gland nodule and a ...retroperitoneal mass and history of functional single atrium and ventricle.
I-metaiodobenzylguanidine scintigraphy showed intense uptake in both lesions. Laboratory investigation demonstrated elevated urinary norepinephrine. Preoperative α-blockade was initiated. A successful open resection of right adrenal and retroperitoneal masses was performed. Pathological examination confirmed PHEO-PGL. Postoperative urinary norepinephrine returned to normal level. A systematic case review in English publications in PubMed and EMBASE suggested a hypothesis that there may exist a possible link between PHEO-PGL and hypoxia from CCHD, which was also indicated in our case. Due to higher risk for PHEO-PGL, a lower threshold of suspicion should be considered in CCHD patients. Therefore, active screening and early treatment of PHEO-PGL are recommended in CCHD patients and clinicians should keep on a long-term follow-up to monitor PHEO-PGL recurrence if hypoxia is not corrected.
Introduction:
Biomarkers predicting tumor response to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) are still lacking despite great efforts. We aimed to assess the ...effectiveness of the immune PET Response Criteria in Solid Tumors
via
SULmax (iPERCIST-max) in predicting tumor response to neoadjuvant immunochemotherapy and short-term survival in locally advanced NSCLC.
Methods:
In this prospective cohort study, we calculated SULmax, SULpeak, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their dynamic percentage changes in a training cohort. We then investigated the correlation between alterations in these parameters and pathological tumor responses. Subsequently, iPERCIST-max defined by the proportional changes in the SULmax response (△SULmax%) was constructed and internally validated using a time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC) value. A prospective cohort from the Sun Yat-Sen University Cancer Center (SYSUCC) was also included for external validation. The relationship between the iPERCIST-max responsiveness and event-free survival in the training cohort was also investigated.
Results:
Fifty-five patients with NSCLC were included in this study from May 2019 to December 2021. Significant alterations in post-treatment SULmax (
p
< 0.001), SULpeak (
p
< 0.001), SULmean (
p
< 0.001), MTV (
p
< 0.001), TLG (
p
< 0.001), and tumor size (
p
< 0.001) were observed compared to baseline values. Significant differences in SULpeak, SULmax, and SULmean between major pathological response (mPR) and non-mPR statuses were observed. The optimal cutoff values of the SULmax response rate were −70.0% and −88.0% using the X-tile software. The univariate and multivariate binary logistic regression showed that iPERCIST-max is the only significant key predictor for mPR status OR = 84.0, 95% confidence interval (CI): 7.84–900.12,
p
< 0.001. The AUC value for iPERCIST-max was 0.896 (95% CI: 0.776–1.000,
p
< 0.001). Further, external validation showed that the AUC value for iPERCIST-max in the SYSUCC cohort was 0.889 (95% CI: 0.698–1.000,
p
= 0.05). Significantly better event-free survival (EFS) in iPERCIST-max responsive disease (31.5 months, 95% CI 27.9–35.1) than that in iPERCIST-max unresponsive disease (22.2 months, 95% CI: 17.3–27.1 months,
p
= 0.024) was observed.
Conclusion:
iPERCIST-max could better predict both early pathological tumor response and short-term prognosis of NSCLC treated with neoadjuvant immunochemotherapy than commonly used criteria. Furthermore, large-scale prospective studies are required to confirm the generalizability of our findings.
A visible-light-induced photocatalytic C–Si formation strategy has been disclosed by uncovering the reactivity of Martin’s spirosilane-derived pentacoordinate silylsilicates as silyl radical ...precursors. The hydrosilylation of a broad spectrum of alkenes and alkynes, as well as the C–H silylation of heteroarenes, has been demonstrated. Remarkably, Martin’s spirosilane was stable and could be recovered via a simple workup process. Furthermore, the reaction proceeded well using water as the solvent or low-energy green LEDs as an alternative energy source.
Abstract
Background and Aims
Familial renal glucosuria (FRG) is a hereditary disorder caused by mutations in SLC5A2, the gene encoding sodium-glucose cotransporter 2 (SGLT2) in proximal tubule cells. ...In this study, we aimed to characterize the genotype-phenotype relationship in FRG patients using data from our cohort and literature review.
Method
We sequenced SLC5A2 in a cohort of 21 FRG patients and measured the renal threshold of glucose (RTG) in 15 patients using urinary glucose excretion in a 4-hour oral glucose tolerance test (OGTT). We built an open-source online calculator to facilitate the calculation of RTG. Besides, we reviewed published literature and obtained information on SLC5A2 variants and 24-hour urinary glucose (24hUG) in FRG patients.
Results
We identified 27 rare SLC5A2 variants, including 13 novel variants (G484D, R564W, A212S, c.574+1G>C, W649*, S592Cfs*6, Q579*, A89T, Y339*, V39F, G491E, A464E, and G360D), in our cohort and yielded 107 SLC5A2 variants from literature review. RTG in our cohort ranged from 1.0 to 9.2mmol/L. Patients carrying two SLC5A2 variants had lower RTG (3.9 vs. 6.2 mmol/L, p = 0.057) and larger amounts of 24-hour urinary glucose excretion (24hUG) (52.39 vs. 7.20 g/1.73m2, p = 2.7*10−8) than those carrying a single variant. Patients with homozygous missense or in-frame indels had mean 24hUG of 82.30g/1.73m2, comparable to those with homozygous truncating variants (81.66g/1.73m2) and significantly more than those with homozygous splicing variants (35.38g/1.73m2, p = 0.026). Patients with homozygous missense variants involving conservative residues had more 24hUG (104.76g/1.73m2) than those with variants at non-conservative residues (46.37g/1.73m2, p = 0.0031).
Conclusion
We built a comprehensive map showing the impact of SLC5A2 variant type, variant location, and zygosity on glucosuria severity. Our results highlighted that conserved residues play an essential role in maintaining the transport function of SGLT2.
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an autoinflammatory disorder without standardized treatment. Janus kinase (JAK) inhibitors can block a range of cytokines ...and might possess significant anti-inflammatory activity. Here, we report the first case of efficacious treatment of refractory SAPHO syndrome with the JAK inhibitor tofacitinib.
A 44-year-old woman presented with arthralgia in the right wrist and complained of having difficulty in doing housework. Symptoms were unresponsiveness to nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and tumor necrosis factor inhibitors. A diagnosis of SAPHO syndrome was made based on previous dermatological and osteoarticular manifestations and bone scintigraphy findings. Oral treatment with tofacitinib at 5 mg twice daily in combination with the basic methotrexate treatment was initiated. After 4 weeks of using tofacitinib, the patient reported marked improvement of symptoms and also reported being competent in completing housework.
The efficacy of JAK inhibitors in treating refractory SAPHO syndrome should be noted.
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