Value of conventional ultrasound and contrast-enhanced ultrasound for the assessment of renal allograft dysfunction and prognosis.

BACKGROUND: Ultrasound (US) is the primary imaging modality for the assessment of transplanted kidneys. This study aims to investigate the ability of conventional US and contrast-enhanced US (CEUS) in assessing renal allograft function and prognosis. METHODS: A total of 78 consecutive renal allograft recipients were enrolled. Patients were classified as normal allograft function (n = 41) and allograft dysfunction (n = 37) groups. All patients underwent US and parameters were measured. The independent-samples t-test or Mann-Whitney U test, logistic regression analysis, Kaplan-Meier survival plots, and Cox regression analysis were used. RESULTS: In multivariable analysis, cortical echo intensity (EI) and cortical peak intensity (PI) were determinant US parameters for renal allograft dysfunction (p = .024 and p = .003, respectively). The combination of cortical EI and PI showed an area under the receiver operating characteristic curve (AUROC) of .785 (p < .001). Of 78 patients (median follow-up: 20mo), 16 (20.5%) exhibited composite end points. Cortical PI had a general prediction accuracy with an AUROC of .691, sensitivity of 87.5%, and specificity of 46.8% at the threshold of 22.08 dB in predicting prognosis (p = .019). The combination of estimated-glomerular filtration rate (e-GFR) and PI in predicting prognosis showed an AUROC of .845 with a cut-off value of .836, sensitivity of 84.0%, and specificity of 67.3% (p < .001). CONCLUSION: This study indicates that cortical EI and PI are useful US parameters for evaluating renal allograft function and e-GFR combined with PI may provide a more accurate predictor of survival.

Assessment of the Peroxisomal Redox State in Living Cells Using NADPH- and NAD+/NADH-Specific Fluorescent Protein Sensors.

The pyridine nucleotides NAD(H) and NADP(H) are key molecules in cellular metabolism, and measuring their levels and oxidation states with spatiotemporal precision is of great value in biomedical research. Traditional methods to assess the redox state of these metabolites are intrusive and prohibit live-cell quantifications. This obstacle was surpassed by the development of genetically encoded fluorescent biosensors enabling dynamic measurements with subcellular resolution in living cells. Here, we provide step-by-step protocols to monitor the intraperoxisomal NADPH levels and NAD+/NADH redox state in cellulo by using targeted variants of iNAP1 and SoNar, respectively.

Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials.

PURPOSE: Bone marrow biopsies (BMB) are performed before/after therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. We sought to establish whether BMB add value in assessing response or predict progression-free survival (PFS) or overall survival (OS) outcomes in follicular lymphoma (FL) subjects in a large, multicenter, multitrial cohort. METHODS: Data were pooled from seven trials of 580 subjects with previously untreated FL through Alliance for Clinical Trials in Oncology (Alliance) and SWOG Cancer Research Network (SWOG) completing enrollment from 2008 to 2016. RESULTS: Only 5/580 (0.9%) had positive baseline BMB, CR on imaging, and subsequent positive BMB (P < .0001). Therefore, BMB were irrelevant to response in 99% of subjects. A sensitivity analysis of 385 FL subjects treated on an Eastern Cooperative Oncology Group study was included. In the Eastern Cooperative Oncology Group cohort, 5/385 (1.3%) had BMB that affected response assessment. Since some subjects do not undergo confirmatory BMB, we performed a landmark survival analysis from first radiologic CR with data from 580 subjects from Alliance and SWOG. Of subjects with CR on imaging (n = 187), PFS and OS were not significantly different among those with negative BMB to confirm CR (n = 47) versus those without repeat BMB (n = 140; PFS: adjusted hazard ratio, 1.10, 95% CI, 0.62 to 1.94, log-rank P = .686; OS: hazard ratio, 0.59, 95% CI, 0.23 to 1.53, log-rank P = .276). CONCLUSION: We conclude that BMB add little value to response assessment in subjects with FL treated on clinical trials and we recommend eliminating BMB from clinical trial requirements. BMB should also be removed from diagnostic guidelines for FL except in scenarios in which it may change management including confirmation of limited stage and assessment of cytopenias. This would reduce cost, patient discomfort, resource utilization, and potentially remove a barrier to trial enrollment.

Impacts of socio-economic determinants, spatial distance and climate factors on the confirmed cases and deaths of COVID-19 in China.

This study is to assess the influences of climate, socio-economic determinants, and spatial distance on the confirmed cases and deaths in the raise phase of COVID-19 in China. The positive confirmed cases and deaths of COVID-19 over the population size of 100,000 over every 5 consecutive days (the CCOPSPTT and DOPSPTT for short, respectively) covered from 25th January to 29th February, 2020 in five city types (i.e., small-, medium-, large-, very large- and super large-sized cities), along with the data of climate, socio-economic determinants, spatial distance of the target city to Wuhan city (DW, for short), and spatial distance between the target city and their local province capital city (DLPC, for short) were collected from the official websites of China. Then the above-mentioned influencing factors on CCOPSPTT and DOPSPTT were analyzed separately in Hubei and other provinces. The results showed that CCOPSPTT and DOPSPTT were significantly different among five city types outside Hubei province (p < 0.05), but not obviously different in Hubei province (p > 0.05). The CCOPSPTT had significant correlation with socio-economic determinants (GDP and population), DW, climate and time after the outbreak of COVID-19 outside Hubei province (p < 0.05), while was only significantly related with GDP in Hubei province (p < 0.05). The DOPSPTT showed significant correlation with socio-economic determinants, DW, time and CCOPSPTT outside Hubei province (p < 0.05), while was significantly correlated with GDP and CCOPSPTT in Hubei province (p < 0.05). Compared with other factors, socio-economic determinants have the largest relative contribution to variance of CCOPSPTT in all studied cities (> 78%). The difference of DOPSPTT among cities was mainly affected by CCOPSPTT. Our results showed that influences of city types on the confirmed cases and death differed between Hubei and other provinces. Socio-economic determinants, especially GDP, have higher impact on the change of COVID-19 transmission compared with other factors.

Low-cost devices with fluorescence spots brightness and size dual-mode readout for the rapid detection of Cr(VI) based on smartphones.

Sensitive, convenient and rapid detection devices for toxic Cr(VI) suitable for filed use are required. Smartphone can be used as the detector, but the quality of images taken with a smartphone may depend on the ambient light and the operator. In this work, two types of low-cost and portable smartphone-based devices used for fluorescence spots brightness and size dual-mode detection of Cr(VI) were constructed with the aid of the 3D printing, which avoids the effect of ambient light and maintains a fixed position of the phone camera relative to the samples. Based on the brightness reflected by the blue channel of RGB values of the images of carbon nanodots, a linear relationship between quenching efficiency and concentration of Cr(VI) in a range of 0.2-150 µM with a limit of detection of 0.058 µM was attained, which is comparable to or better than that from fluorescence spectrometers. With the size variation of fluorescence spots, a linear range of 10-350 µM was acquired and it is more intuitive for direct naked-eye estimation of the concentration of Cr(VI). The applicability of the proposed devices for the detection of Cr(VI) was verified with water and soil samples with recoveries ranging in 95.0-108.2%.

Contrast-enhanced ultrasonography for assessment of tubular atrophy/interstitial fibrosis in immunoglobulin A nephropathy: a preliminary clinical study.

PURPOSE: To investigate the potential of contrast-enhanced ultrasonography (CEUS) for evaluating the severity of tubular atrophy/interstitial fibrosis (TA/IF) in immunoglobulin A nephropathy (IgAN) patients. MATERIALS AND METHODS: A total of 80 patients with IgAN and 33 healthy adults were investigated. Patients were divided into three groups according to the TA/IF (T) grade of the Oxford classification: T0 (n = 28), T1 (n = 35), and T2 (n = 17). Patients and control subjects underwent conventional ultrasound (US) and CEUS. Time-intensity curves of CEUS were drawn for regions of interest located in the renal cortex and medulla using QLab software. Conventional US and CEUS quantitative parameters were analyzed. One-way analysis of variance (ANOVA), binary logistic regression, and receiver operating characteristic (ROC) curves were used. RESULTS: There were no significant differences in renal size, cortical thickness, and medullary perfusion parameters (P > 0.05), whereas the differences in peak intensity (PI), area under the time-intensity curve (AUC) and wash-in slope (WIS) of cortical perfusion parameters between the control subjects and patients were significant (P < 0.05). PI was significantly lower with the increasing degree of T (P < 0.05). PI was associated independently with the degree of T in IgAN patients (P < 0.05). ROC analysis revealed that using the optimal cutoff values of 15.38 dB for diagnosis of T0-T1 (sensitivity 83.30% and specificity 63.00%) and 14.69 dB for diagnosis of T2 (sensitivity 100.00% and specificity 66.70%), the corresponding areas under the ROC curve were found to be 0.782 and 0.952, respectively. CONCLUSIONS: CEUS can potentially be used as a noninvasive imaging marker to evaluate the severity of TA/IF in IgAN patients.

Quantitative parameters of contrast-enhanced ultrasonography for assessment of renal pathology: A preliminary study in chronic kidney disease.

OBJECTIVE: To assess the severity of renal pathology in patients with chronic kidney disease (CKD) using contrast-enhanced ultrasonography (US). METHODS: 275 patients with CKD who were proven by renal biopsy and 30 healthy adults were examined using conventional US and contrast-enhanced US. Ultrasonic parameters included renal length, cortical thickness, rise time (RT), peak intensity (PI), area under the time-intensity curve (AUC), wash-in slope (WIS) and time to peak (TTP). Based on pathological scores, CKD patients were classified into mild, and moderate to severe CKD groups. The logistic regression analysis and receiver operating characteristic (ROC) curves were used. RESULTS: PI and AUC differed significantly among the controls, mild and moderate to severe CKD groups (P < 0.05). There was significant difference in PI among the different pathology types (P < 0.05). The multivariate logistic regression analysis showed that PI was associated independently with the severity of renal pathology in patients with CKD (P < 0.05). PI less than 13.87 dB had a certain diagnostic ability, and the sensitivity and specificity were 72.5% and 64.0%, respectively. CONCLUSIONS: Contrast-enhanced US may be useful for noninvasive assessment of the severity of renal pathology. PI may be potentially valuable for guiding therapy and follow-up in patients with CKD.

China's natural wetlands: past problems, current status, and future challenges.

Natural wetlands, occupying 3.8% of China's land and providing 54.9% of ecosystem services, are unevenly distributed among eight wetland regions. Natural wetlands in China suffered great loss and degradation (e.g., 23.0% freshwater swamps, 51.2% costal wetlands) because of the wetland reclamation during China's long history of civilization, and the population pressure and the misguided policies over the last 50 years. Recently, with an improved understanding that healthy wetland ecosystems play a vital role in her sustainable economic development, China started major efforts in wetland conservation, as signified by the policy to return reclaimed croplands to wetlands, the funding of billions of dollars to restore degraded wetlands, and the national plan to place 90% of natural wetlands under protection by 2030. This paper describes the current status of the natural wetlands in China, reviews past problems, and discusses current efforts and future challenges in protecting China's natural wetlands.