Diabetes duration or age at onset and mortality in insulin-dependent diabetics: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis was conducted given the contradictory findings from studies on the influence of diabetes duration or age at onset on mortality in patients with insulin-dependent diabetes mellitus (IDDM). METHODS: Electronic databases (PubMed, Embase, Cochrane, Web of Knowledge, Scopus, and CINHAL) were comprehensively searched to identify relevant studies until October 31, 2022. All of the selected articles contained statistics on hazard ratios, relative risks (RRs), or odds ratios, or data for estimating the association between diabetes duration or age at onset and total mortality in IDDM patients. Regardless the heterogeneity assessed by the I2 statistic, pooled RRs and 95% confidence intervals (CI) for total mortality were acquired via random effect meta-analysis with inverse variance weighting. RESULTS: This meta-analysis finally included 19 studies involving 122, 842 individuals. Both age at onset and diabetes duration were positively associated with an increased mortality rate in IDDM patients. Specifically, the pooled RRs for age at onset and diabetes duration were 1.89 (95%CI 1.43-2.50) and 1.89 (95%CI 1.16-3.09) respectively. Subgroup analyses revealed that only prepubertal onset was associated with a greater survival advantage than pubertal or postpubertal onset. CONCLUSIONS: The findings of this meta-analysis and systematic review suggest that a later age at onset or longer diabetes duration is associated with increased risk of total mortality in IDDM patients. However, this conclusion shall be interpreted with caution due to the possibility of residual confounding and be confirmed in the future by well-designed studies.

Sub-50 nm core-shell nanoparticles with the pH-responsive squeezing release effect for targeting therapy of hepatocellular carcinoma.

The development of drug delivery systems with high drug loading capacity, low leakage at physiological pH, and rapid release at the lesion sites remains an ongoing challenge. In this work, core-shell poly(6-O-methacryloyl-D-galactose)@poly(tert-butyl methacrylate) (PMADGal@PtBMA) nanoparticles (NPs) of sub-50 nm are facilely synthesized by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization with the assistance of 12-crown-4. A hydrophilic poly(methacrylic acid) (PMAA) core can then be revealed after deprotection of the tert-butyl groups, which is negatively charged and can adsorb nearly 100% of incubated doxorubicin (DOX) from a solution at pH 7.4. The physical shrinkage of PMAA chains below pH 6.0 endows the core with the squeezing effect, therefore realizing rapid drug release. It is demonstrated that the DOX release rate of PMADGal@PMAA NPs at pH 5 was 4 times that at pH 7.4. Cellular uptake experiments confirm the high targeting ability of the galactose modified PMADGal shell to human hepatocellular carcinoma (HepG2) cells. The fluorescence intensity of DOX in HepG2 cells is 4.86 times that of HeLa cells after 3 h incubation. Moreover, 20% cross-linked NPs show the highest uptake efficiency by HepG2 cells due to their moderate surface charge, size and hardness. In summary, both the core and the shell of PMADGal@PMAA NPs promise the rapid site-specific release of DOX in HepG2 cells. This work provides a facile and an effective strategy to synthesize core-shell NPs for hepatocellular carcinoma targeting therapy.

Galactosylated Core-Shell Nanoparticles with pH/GSH Dual Sensitivity for Targeting Hepatocellular Carcinoma.

Galactosylated core-shell nanoparticles (NPs) with diameters of sub-50 nm were fabricated in one pot by reversible addition-fragmentation chain transfer (RAFT) soap-free emulsion polymerization. Their galactosylated shells and acidic cores endow them with high targeting and drug loading efficiencies, respectively. Morever, the physical shrinkage and cleavage of the disulfide cross-linked NPs can realize the rapid release of loaded doxorubicin (DOX) under pH 5.0 and reduced glutathione (GSH) conditions. The combination of these excellent properties resulted in an even lower IC50 of DOX-loaded NPs than free DOX, demonstrating that this platform would be promising in targeting the therapy of hepatocellular carcinoma.

Differentiating thymoma, thymic carcinoma and lymphoma based on collagen fibre patterns with T2- and diffusion-weighted magnetic resonance imaging.

OBJECTIVES: The amount and distribution of intratumoural collagen fibre vary among different thymic tumours, which can be clearly detected with T2- and diffusion-weighted MR images. To explore the incidences of collagen fibre patterns (CFPs) among thymomas, thymic carcinomas and lymphomas on imaging, and to evaluate the efficacy and reproducibility of CFPs in differential diagnosis of thymic tumours. MATERIALS AND METHODS: Three hundred and ninety-eight patients with pathologically diagnosed thymoma, thymic carcinoma and lymphoma who underwent T2- and diffusion-weighted MR imaging were retrospectively enrolled. CFPs were classified into four categories: septum sign, patchy pattern, mixed pattern and no septum sign. The incidences of CFPs were compared among different thymic tumours, and the efficacy and reproducibility in differentiating the defined tumour types were analysed. RESULTS: There were significant differences in CFPs among thymomas, thymic squamous cell carcinomas (TSCCs), other thymic carcinomas and neuroendocrine tumours (OTC&NTs) and thymic lymphomas. Septum signs were found in 209 (86%) thymomas, which differed between thymomas and any other thymic neoplasms (all p < 0.005). The patchy, mixed patterns and no septum sign were mainly seen in TSCCs (80.3%), OTC&NTs (78.9%) and thymic lymphomas (56.9%), respectively. The consistency of different CFP evaluation between two readers was either good or excellent. CFPs achieved high efficacy in identifying the thymic tumours. CONCLUSION: The CFPs based on T2- and diffusion-weighted MR imaging were of great value in the differential diagnosis of thymic tumours. KEY POINTS: • Significant differences are found in intratumoural collagen fibre patterns among thymomas, thymic squamous cell carcinomas, other thymic carcinomas and neuroendocrine tumours and thymic lymphomas. • The septum sign, patchy pattern, mixed pattern and no septum sign are mainly seen in thymomas (86%), thymic squamous cell carcinomas (80.3%), other thymic carcinomas and neuroendocrine tumours (79%) and thymic lymphomas (57%), respectively. • The collagen fibre patterns have high efficacy and reproducibility in differentiating thymomas, thymic squamous cell carcinomas and thymic lymphomas.

Can the low and high b-value distribution influence the pseudodiffusion parameter derived from IVIM DWI in normal brain?

BACKGROUND: Our study aims to reveal whether the low b-values distribution, high b-values upper limit, and the number of excitation (NEX) influence the accuracy of the intravoxel incoherent motion (IVIM) parameter derived from multi-b-value diffusion-weighted imaging (DWI) in the brain. METHODS: This prospective study was approved by the local Ethics Committee and informed consent was obtained from each participant. The five consecutive multi-b DWI with different b-value protocols (0-3500 s/mm2) were performed in 22 male healthy volunteers on a 3.0-T MRI system. The IVIM parameters from normal white matter (WM) and gray matter (GM) including slow diffusion coefficient (D), fast perfusion coefficient (D*) and perfusion fraction (f) were compared for differences among defined groups with different IVIM protocols by one-way ANOVA. RESULTS: The D* and f value of WM or GM in groups with less low b-values distribution (less than or equal to 5 b-values) were significantly lower than ones in any other group with more low b-values distribution (all P <  0.05), but no significant differences among groups with more low b-values distribution (P > 0.05). In addition, no significant differences in the D, D* and f value of WM or GM were found between group with one and more NEX of low b-values distribution (all P > 0.05). IVIM parameters in normal WM and GM strongly depended on the choice of the high b-value upper limit. CONCLUSIONS: Metrics of IVIM parameters can be affected by low and high b value distribution. Eight low b-values distribution with high b-value upper limit of 800-1000 s/mm2 may be the relatively proper set when performing brain IVIM studies.

Predicting pathological subtypes and stages of thymic epithelial tumors using DWI: value of combining ADC and texture parameters.

OBJECTIVES: To explore the value of combining apparent diffusion coefficients (ADC) and texture parameters from diffusion-weighted imaging (DWI) in predicting the pathological subtypes and stages of thymic epithelial tumors (TETs). METHODS: Fifty-seven patients with TETs confirmed by pathological analysis were retrospectively enrolled. ADC values and optimal texture feature parameters were compared for differences among low-risk thymoma (LRT), high-risk thymoma (HRT), and thymic carcinoma (TC) by one-way ANOVA, and between early and advanced stages of TETs were tested using the independent samples t test. Receiver operating characteristic (ROC) curve analysis was performed to determine the differentiating efficacy. RESULTS: The ADC values in LRT and HRT were significantly higher than the values in TC (p = 0.004 and 0.001, respectively), also in early stage, values were significantly higher than ones in advanced stage of TETs (p < 0.001). Among all texture parameters analyzed in order to differentiate LRT from HRT and TC, the V312 achieved higher diagnostic efficacy with an AUC of 0.875, and combination of ADC and V312 achieved the highest diagnostic efficacy with an AUC of 0.933, for differentiating the LRT from HRT and TC. Furthermore, combination of ADC and V1030 achieved a relatively high differentiating ability with an AUC of 0.772, for differentiating early from advanced stages of TETs. CONCLUSIONS: Combination of ADC and DWI texture parameters improved the differentiating ability of TET grades, which could potentially be useful in clinical practice regarding the TET evaluation before treatment. KEY POINTS: • DWI texture analysis is useful in differentiating TET subtypes and stages. • Combination of ADC and DWI texture parameters may improve the differentiating ability of TET grades. • DWI texture analysis could potentially be useful in clinical practice regarding the TET evaluation before treatment.

Iodine Quantification Using Dual-Energy Computed Tomography for Differentiating Thymic Tumors.

The aim of the study was to explore the efficacy of iodine quantification with dual-energy computed tomography (DECT) in differentiating thymoma, thymic carcinoma, and thymic lymphoma. MATERIALS AND METHODS: Fifty-seven patients with pathologically confirmed low-risk thymoma (n = 16), high-risk thymoma (n = 15), thymic carcinoma (n = 14), and thymic lymphoma (n = 12) underwent chest contrast-enhanced DECT scan were enrolled in this study. Tumor DECT parameters including iodine-related Hounsfield unit (IHU), iodine concentration (IC), mixed HU (MHU), and iodine ratio in dual phase, slope of energy spectral HU curve (λ), and virtual noncontrast (VNC) were compared for differences among 4 groups by one-way analysis of variance. Receiver operating characteristic curve was used to determine the efficacy for differentiating the low-risk thymoma from other thymic tumor by defined parameters. RESULTS: According to quantitative analysis, dual-phase IHU, IC, and MHU values in patients with low-risk thymoma were significantly increased compared with patients with high-risk thymoma, thymic carcinoma, and thymic lymphoma (P < 0.05/4).The venous phase IHU value yielded the highest performance with area under the curve of 0.893, 75.0% sensitivity, and 89.7% specificity for differentiating the low-risk thymomas from high-risk thymomas or thymic carcinoma at the cutoff value of 34.3 HU. When differentiating low-risk thymomas from thymic lymphoma, the venous phase IC value obtained the highest diagnostic efficacy with the area under the curve of 0.969, and sensitivity, specificity, and cutoff value were 87.5%, 100.0%, and 1.25 mg/mL, respectively. CONCLUSIONS: Iodine quantification with DECT may be useful for differentiating the low-risk thymomas from other thymic tumors.

Usefulness of Volume Perfusion Computed Tomography in Differentiating Histologic Subtypes of Thymic Epithelial Tumors.

PURPOSE: This study aimed to evaluate the usefulness of volume perfusion computed tomography (VPCT) parameters in differentiating the World Health Organization subtypes of thymic epithelial tumors. MATERIALS AND METHODS: This study was approved by the local ethics committee, and informed written consent was obtained. Fifty-one thymic epithelial tumor patients confirmed by histopathological analysis underwent conventional CT and a 48-second VPCT scan of the tumor bulk before any treatment. The VPCT parameters (blood volume [BV], blood flow [BF], mean transit time [MTT], and permeability [PMB]) based on volume of interest (VOI) or region of interest (ROI) were compared for differences among low-risk thymomas (LRTs; types A, AB, and B1), high-risk thymomas (HRTs; types B2 and B3) and thymic carcinomas (TCs) by one-way analysis of variance. RESULTS: The BVVOI, PMBVOI, BVROI, and PMBROI values in LRT were significantly higher than the values from HRT and thymic carcinoma (BVVOI: 13.75, 6.17, and 5.48 mL/100 mL; PMBVOI: 22.47, 9.56, and 13.37 mL/100 mL/min; BVROI: 14.75, 6.87, and 6.06 mL/100 mL; PMBROI: 24.05, 9.79, and 15.63 mL/100 mL/min, respectively; all P < 0.05/3). However, the BFVOI, MTTVOI, BFROI, and MTTROI values did not differ between LRT and HRT or thymic carcinoma groups (P > 0.05/3). CONCLUSIONS: These results suggest that VPCT could be useful in differentiating LRTs from HRTs and TCs preoperatively.

Incidence and clinical variable inter-relationships of thymic epithelial tumors in northwest China.

BACKGROUND: Thymic epithelial tumors (TETs) are the most common primary thymus tumors, but neither the possible ethnical/regional differences in the incidence of TETs nor the inter-relationships among the clinical variables has been revealed in northwest China. METHODS: A retrospective chart review was performed among pathologically confirmed TET patients from January 2004 to December 2015 in a tertiary general hospital of northwest China and the incidence, clinical features and the inter-relationships among clinical variables were analyzed. RESULTS: A total of 603 pathologically confirmed TETs patients (age range, 5-78 years; 308 males) were enrolled and the most common lesion location was anterior mediastinum (98.5%), among them, 192 (31.8%) had myasthenia gravis (MG). Twenty-six (5.7%), 112 (24.6%), 83 (18.2%), 137 (30.1%), 74 (16.3%), and 23 (5.1%) patients fell into the World Health Organization (WHO) type A, AB, B1, B2, B3 and thymic carcinoma (TC), respectively. The incidence of TETs was slightly higher in the female population and the age group of 40-60 years old. In addition, MG predominantly coexisted with WHO types A-B3 TETs and the TETs with MG were smaller than those without MG. The correct diagnosis rates were 42.3% (77 out of 182), 61.1% (127 out of 208), 89.3% (250 out of 280) and 75.0% (3 out of 4) for chest X-ray, non-contrast computed tomography (CT), contrast CT scan and magnetic resonance imaging (MRI), respectively. CONCLUSIONS: Distinct gender and age differences exist in the incidence of TETs and the A-B3 TETs are closely related with MG. Contrast CT scan plays more important role in diagnosing TETs.

Intravoxel incoherent motion diffusion-weighted MR imaging parameters predict pathological classification in thymic epithelial tumors.

We evaluated the performance of intravoxel incoherent motion (IVIM) parameters for preoperatively predicting the subtype and Masaoka stage of thymic epithelial tumors (TETs). Seventy-seven patients with pathologically confirmed TETs underwent a diffusion weighted imaging (DWI) sequence with 9 b values. Differences in the slow diffusion coefficient (D), fast perfusion coefficient (D*), and perfusion fraction (f) IVIM parameters, as well as the multi b-value fitted apparent diffusion coefficient (ADCmb), were compared among patients with low-risk (LRT) and high-risk thymomas (HRT) and thymic carcinomas (TC), and between early stage (stages I and II) and advanced stage (stages III and IV) TET patients. ADCmb, D, and D* values were higher in the LRT group than in the HRT or TC group, but did not differ between the HRT and TC groups. The mean ADCmb, D, and D* values were higher in the early stage TETs group than the advanced stage TETs group. The f values did not differ among the groups. These results suggest that IVIM DWI could be used to preoperatively predict subtype and Masaoka stage in TET patients.

Predicting subtypes of thymic epithelial tumors using CT: new perspective based on a comprehensive analysis of 216 patients.

It is highly necessary to identify low versus high risk thymic epithelial tumors (TETs) before operation to guide optimal treatment strategies. Current CT diagnostic parameters could not effectively achieve this goal. We evaluated three parameters of CT scan in a cohort of 216 TETs patients. Parameters of contrast enhancement, risk of aggressiveness, and nodule with fibrous septum were evaluated in low (A, AB) versus high risk (B1, B2, B3 and thymic carcinoma) TETs. Grade of contrast enhancement showed predictive value in classifying low and high risk TETs well. A maximal contrast-enhanced range of 25.5 HU could produce 78.8% sensitivity and 68.5% specificity in determining low risk subtypes. Additionally, risk of aggressiveness parameter was demonstrated to be associated with TETs subtype (r = 0.801, P < 0.001) and may add confidence in determining low versus high risk subtypes. Furthermore, multiple nodule with fibrous septum could suggest subtype AB. Findings from this study support role of studied parameters of CT manifestations in predicting the low and high risk stages of TETs. These findings provide empirical evidence for incorporating these parameters in clinical practice for identifying TETs stage before operation, if validated in additional studies.