[Diagnostic value of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in fever of unknown origin].

OBJECTIVE: To evaluate the diagnostic value of fluorine-18 fluorodeoxyglucose (¹8F-FDG) positron emission tomography/computed tomography (PET/CT) in fever of unknown origin (FUO) in a Chinese hospital. METHODS: The records of 51 patients with FUO (32 men and 19 women; mean age 54 years with a range between 3 and 81 years) were analyzed retrospectively. All the patients were examined by ¹8F-FDG PET/CT scan and the results were compared with the final diagnosis which was established by additional procedures including pathology, laboratory examination, and clinical follow-up for more than 3 months. The t test was used for statistical analysis. RESULTS: A final diagnosis was established for 48 patients, including 32 patients with infectious diseases, 9 with malignancies, and 7 with non-infectious inflammatory diseases. By FDG PET scan alone, the rates of true positive, false positive, false negative, and true negative were 52.9%, 27.5%, 17.6%, and 2.0%, respectively. By FDG PET/CT scan, the rates of true positive, false positive, false negative, and true negative were 70.6%, 27.5%, 2.0%, and 0, respectively. ¹8F-PET/CT had a sensitivity of 97.3% (36/37), specificity of 0 (0/14), and accuracy of 70.6% (36/51) in FUO, especially a high sensitivity and accuracy of 100% (9/9) in the diagnosis of malignant tumor. Moreover, the maximum standardized uptake value (SUVmax) in tumor was significant higher than that in infection (3.7 ± 2.7 vs. 7.7 ± 3.5, P=0.001, t=3.6), which implied that SUVmax might be useful in differential diagnosis in FUO. CONCLUSION: FDG PET/CT is a valuable imaging tool for the identification and location of the potential lesion in FUO and is helpful for the etiological diagnosis, especially in the diagnosis of malignant lesions.

[Efficiency evaluation of diuretic renography in the operative or conservative treatments of unilateral ureteropelvic junction obstruction patients].

OBJECTIVE: To analyze the efficiency of diuretic renography in the management of unilateral ureteropelvic junction obstruction (UPJO) patients, by observing the affected kidney relative renal function (RRF) and drainage in the period of follow-up. METHODS: In the study, 76 patients diagnosed as unilateral UPJO were retrospectively collected. Diuretic renography was performed on all the patients initially, and during the period of follow-up. No morphological or functional abnormalities were detected on the contralateral kidney. Changes of affected renal RRF and drainage were observed during the follow-up period. The correlations of initial RRF (RRFinitial) and drainage type with RRF improvement were analyzed. RESULTS: In the operative group (57 cases), the RRFinitial of affected kidney was 40.81%±12.96%, and the RRF in the last follow-up (RRFrecent) was 44.63%±13.21% (P<0.05). Drainage improvements was found in 54.00% of the obstructive patients (27/50), and unchanged in 71.43% of the non-obstructive patients (5/7). In the conservative group (19 cases), the RRFinitial was 46.47%±12.84%, and the RRFrecent was 46.95%±11.86% (P>0.05). One obstructive patient (1/10) was found with improved drainage, and the other 9 obstructive patients (9/10) and all of the non-obstructive patients (9/9) were observed with unchanged drainage. Four patients with deteriorated RRF in the conservative group received surgery. There were no significant differences in the changes of affected renal RRF in different RRFinitial and drainage types in both operative and conservative groups. CONCLUSION: Diuretic renography could be effectively applied in the follow-up of unilateral UPJO patients. Operation could improve affected kidney's RRF, and better some patients' drainage conditions. However, for those patients with no or minor clinical symptoms, conservative management could be accepted if RRF remains stable during the period of follow up.

[Metabolic activity measured by ¹8F-FDG PET/CT in newly diagnosed patients with non-Hodgkin lymphoma: correlation with immunophenotype].

OBJECTIVE: To compare the metabolic activity by ¹8F-fluorodeoxyglucose (¹8F-FDG) uptake across the various histologic subtypes of non-Hodgkin lymphoma (NHL) and to investigate the relationship between metabolic activity and immunophenotype. METHODS: Positron emission tomography/computed tomography (PET/CT) studies of patients with newly diagnosed NHL from Jul 2010 to Mar 2012 were retrospectively reviewed, 82 patients were enrolled in our study according to the inclusion and exclusion criteria. The maximum standardized uptake value (SUVmax) of each patient reflecting the metabolic activity was recorded. Mean SUVmax of aggressive B-cell NHL, indolent B-cell NHL and T-cell NHL were compared. Pearson and Spearman test were used to analyze the relationship between SUVmax and immunophenotype. RESULTS: The SUVmax of various subtypes of lymphoma revealed a wide range from 0.9 to 40.3, but lesions of 79 patients in this study showed obviously FDG uptake. SUVmax of indolent B-cell NHL (4.5 ± 2.4) was significantly lower than that of aggressive B-cell NHL (13.1 ± 7.6) (P = 0.000), T-cell NHL (8.0 ± 3.8) (P = 0.03). SUVmax of aggressive B-cell NHL was significantly higher than that of indolent B-cell NHL, T-cell NHL (P = 0.000, P = 0.005). SUVmax of B-cell NHL had positive correlation with Ki-67 expression (r = 0.493, P = 0.001) and negative correlation with CD138 (r = -0.654, P = 0.008). While SUVmax of T-cell NHL had no correlation with Ki-67 expression (P = 0.213), but had negative correlation with CD56 (r = -0.545, P = 0.044). CONCLUSIONS: Different subtype of NHL manifests markedly different intensity of FDG uptake, but most lesions of lymphoma are FDG avid. Metabolic activity is lower in indolent B-cell NHL than in aggressive B-cell NHL and T-cell lymphoma, which is concordant with its aggressiveness. SUVmax of B-cell NHL correlates with expression of Ki-67 and CD138. SUVmax of T-cell NHL is associated with the expression of CD56, no correlation is detected between SUVmax of T-cell NHL and Ki-67 proliferation.

HSPA5 forms specific complexes with copper.

Our previous study indicated that Hspa5 directly interacts with copper (Cu) to maintain Cu homeostasis in astrocytes. In this study, we explored the possibility that Cu forms a specific complex with Hspa5 by assaying stoichiometric binding of Cu and other metals to recombinant human HSPA5 (rh-HSPA5) in silico. Spectrophotometric analysis showed that incubation of rh-HSPA5 with Cu but not with Fe, Mn, Zn, or Pb in the presence of ascorbic acid produced an absorbance peak at 470 nm. Furthermore, the absorbance peak was absent when bovine serum albumin was incubated with Cu and when another recombinant protein YWHAZ-14-3-3-Zeta carrying a 6× histidine tag identical to the tag in the rh-HSPA5 was incubated with Cu. The absorbance peak produced by Cu and rh-HSPA5 was abolished by EDTA treatment and was stabilized at pH levels above 6.5. Assay of the stoichiometry of metal binding to the purified rh-HSPA5 showed that one molecule of the rh-HSPA5 could chelate 1 or 2 Cu, 13 iron (Fe), 5 zinc (Zn) and 10 lead (Pb) ions but not manganese (Mn). These data further support our previous finding that HSPA5 specifically forms a complex with Cu to help maintain Cu homeostasis.

Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with primary T cell lymphomas.

OBJECTIVE: T cell lymphomas are associated with an aggressive worse prognosis. This study is designed to assess T cell lymphomas using 18F-FDG PET/CT. METHODS: Sixty-four patients with newly diagnosed T cell lymphomas underwent PET/computed tomography (PET/CT) scans, 47 cases who were fully followed up were retrospectively reviewed and analyzed. Overall survival (OS) and progression-free survival (PFS) were recorded for prognosis. We measured the maximum standardized uptake value (SUVmax) in all cases, analyzed the correlation between SUVmax and survival and other clinicopathologic parameters. Kaplan-Meier log-rank tests were then used to compare the survival of high and low PET/CT parameter groups, and multivariate Cox proportional hazards regression analysis was carried out to identify predictors of OS and PFS. RESULTS: With a median follow-up of 26.5 (range 0.7-117.5) months, the 1-, 2- and 3-year OS were 75.6, 61.7 and 49.2%, and PFS were 49.3, 39.9 and 29.9%, respectively in 47 patients. Among them, 33 cases progressed with a median time of 9.5 (0.7-115.0) months, and 26 patients died with a median survival time of 26.5 (0.7-117.5) months. Multivariate analysis showed the following independent prognostic factors for OS: age >60 years (P = 0.002), SUVmax >9.7 (P = 0.009) and extranodal involvement of more than one site (P = 0.018). In addition, lactate dehydrogenase level (P = 0.003) and B symptoms (P = 0.018) were independent risk factors for PFS. CONCLUSION: Pretherapy SUVmax may serve as an independent predictor of outcome in patients with newly diagnosed T cell lymphomas.

Component-Based Design and Assembly of Heuristic Multiple Sequence Alignment Algorithms.

In recent years, there has been an explosive increase in the amount of bioinformatics data produced, but data are not information. The purpose of bioinformatics research is to obtain information with biological significance from large amounts of data. Multiple sequence alignment is widely used in sequence homology detection, protein secondary and tertiary structure prediction, phylogenetic tree analysis, and other fields. Existing research mainly focuses on the specific steps of the algorithm or on specific problems, and there is a lack of high-level abstract domain algorithm frameworks. As a result, multiple sequence alignment algorithms are complex, redundant, and difficult to understand, and it is not easy for users to select the appropriate algorithm, which may lead to computing errors. Here, through in-depth study and analysis of the heuristic multiple sequence alignment algorithm (HMSAA) domain, a domain-feature model and an interactive model of HMSAA components have been established according to the generative programming method. With the support of the PAR (partition and recur) platform, the HMSAA algorithm component library is formalized and a specific alignment algorithm is assembled, thus improving the reliability of algorithm assembly. This work provides a valuable theoretical reference for the applications of other biological sequence analysis algorithms.

Research on Components Assembly Platform of Biological Sequences Alignment Algorithm.

After years of development, the complexity of the biological sequence alignment algorithm is gradually increasing, and the lack of high abstract level domain research leads to the complexity of its algorithm development and improvement. By applying the idea of software components to the design and development of algorithms, the development efficiency and reliability of biological sequence alignment algorithms can be effectively improved. The component assembly platform applies related assembly technology, which simplifies the operation difficulty of component assembly and facilitates the maintenance and optimization of the algorithm. At the same time, a friendly visual interface is used to intuitively complete the assembly of algorithm components, and an executable sequence alignment algorithm program is obtained, which can directly carry out alignment computing.

Is the bullhead sign on bone scintigraphy really common in the patient with SAPHO syndrome? A single-center study of a 16-year experience.

OBJECTIVE: The aim of this study was to assess the bone lesion distribution and analyze the frequency of the bullhead sign in patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome using whole-body bone scintigraphy (WBBS) in a relatively populous study population. METHODS: In this study, the Nuclear Medicine Department's records of one center were retrospectively reviewed and the patients who fulfilled the diagnostic criteria for SAPHO syndrome and underwent Tc-99m-methylene diphosphonate WBBS were identified over a 16-year period. The following data were collected from patients, including age, sex, surgically proved pathology of the bone lesions, WBBS surveillance interval, and SAPHO syndrome components. The bone lesion distribution and the frequency of bullhead sign involving the manubrium and bilateral sternoclavicular junctions were analyzed. RESULTS: Forty-eight patients were enrolled in this study. The initial WBBS indicated bone involvement in all of the 48 (100%) patients, in whom the most commonly affected region was the anterior chest wall (ACW) (100%, 48/48). The frequency of the upper costosternal junction involvement was the highest (38/48, 79.2%), and 28.9% (11/38) patients were found to show isolated involvement of the first rib in ACW. The frequency of the bullhead sign was only 22.9% (11/48, 95% CI: 12.0-37.3). In the eight (16.7%, 8/48) patients who were followed up using WBBS with an interval that ranged from 1 to 10 years, one patient with an initially single sternoclavicular junction lesion developed a typical bullhead sign over 10 years; other patients with or without the initial typical bullhead sign showed stable appearance over 1-4 years. CONCLUSION: This retrospective study shows that in patients with proposed SAPHO syndrome, the bone lesions are most likely located in ACW, and the configuration of the bullhead sign is characteristic, but not entirely sensitive. The value of upper costosternal junction involvement, especially the first rib, may be underevaluated.

[Study of clinical value of dual-phase imaging using single photon emission computed tomography with coincidence detection for differentiating benign from malignant lesions].

OBJECTIVE: To investigate the clinical value of dual-phase imaging of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) using single photon emission computed tomography with coincidence detection (SPECT with coincidence) for differentiating benign and malignant lesions. METHODS: Thirty patients with unknown lesions from June 2003 to March 2004 in our hospital were enrolled in this study. All patients underwent dual-phase imaging of 18F-FDG SPECT with coincidence. The early images were obtained 60 min post injection. And the patients were divided into 2 groups, one receiving delayed scans at 210 min after 18F-FDG injection and the other at 270 min. Lesion status was determined by pathologic findings or by clinical follow-up. RESULTS: Forty-eight lesions (30 malignant and 18 benign lesions verified by pathologic findings or clinical follow-up) of 30 patients were detected by dual-phase imaging, in which there were 29 true positive results, 15 true negative, 3 false positive and 1 false negative. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of dual-phase imaging were 96.7%, 83.3%, 91.6%, 90.6%, and 93.8%, respectively. Those of early imaging and CT were 93.3%, 72.2%, 85.4%, 84.8%, 86.7% and 76.9%, 57.1%, 70.0%, 76.9%, 57.1%, respectively. The T/NT of all malignant lesions (except 1 false negative case) in delayed imaging were significantly increased (t=-3.071, P<0.01). However, there were no statistical differences in the T/NT of benign lesions (t=0.398, P=0.695) between early and delayed imagings. CONCLUSION: Dual-phase imaging of FDG SPECT with coincidence provides benefit for differentiating benign and malignant lesions.

Delayed renal tissue tracer transit in Tc-99m-DTPA renography correlates with postoperative renal function improvement in UPJO patients.

OBJECTIVE: The aim of the study was to explore the potential parameters for evaluating the improvement in relative renal function (RRF) in patients with unilateral ureteropelvic junction obstruction (UPJO) who underwent surgery. In this regard we observed the RRF expressed as the obstructed kidney's percentage contribution to overall renal function in technetium-99m diethylenetriaminepentaacetic acid (Tc-99m-DTPA) diuretic renography. MATERIALS AND METHODS: Data on 47 patients, who underwent Anderson-Hynes pyeloplasty for diagnosed unilateral UPJO during the period of February 2003 to October 2014, were retrospectively collected. Tc-99m-DTPA diuretic renography was performed on all patients before and after surgery, and no morphological or functional abnormalities were detected on the contralateral kidney. Several parameters, especially renal tissue tracer transit (TTT), the response to furosemide stimulation, and RRF, were evaluated. All data were analyzed with the statistical software SPSS, 17.0, and a value of P less than 0.05 was considered statistically significant. RESULTS: Data on 42 patients were eventually retained for further analysis; five patients were excluded because of indeterminate TTT. All patients showed obstructive response to furosemide stimulation with a preoperative RRF of 41±12%. Postoperative RRF of the obstructed kidneys was 47±11%, significantly higher than the preoperative RRF (P<0.05). Postoperative RRF improvement (absolute increment≥5%) was seen in 18/42 (43%) patients, and 24/42 (57%) of them manifested with postoperative drainage improvement. After surgery, both the RRF increment and the percentage of patients with postoperative RRF improvement in the preoperative delayed TTT group were significantly higher than those in the normal TTT group (12±7 vs. 2±4%, and 81 vs. 19%, respectively; P<0.05), but no significant difference in postoperative drainage improvement was detected between the two groups (56 vs. 54%, P>0.05). None of the other factors, including the preoperative RRF, obstructed kidney location, surgical method, sex, and age, had a significant influence on postoperative RRF improvement (P>0.05). CONCLUSION: Preoperatively delayed TTT of Tc-99m-DTPA diuretic renography was an independent factor that correlated with RRF improvement of unilaterally hydronephrotic kidneys, and might provide valuable information for surgical decisions pertaining to UPJO patients.

[Measurement of glomerular filtration rate with renal dynamic imaging: comparison with two-sample method].

OBJECTIVE: To compare the estimation of glomerular filtration rate (GFR) by renal dynamic imaging with that estimated by two-sample method and evaluate the reliability of measurement of GFR by renal dynamic imaging. METHODS: The study was performed in 54 patients (33 males and 21 females; aged 15 to 82 years) with primary or secondary chronic nephrosis. The patients were intravenously bolus injected with 185 MBq /1mL of (99)Tc(m)-DTPA 20 min after drinking 300 mL of water. Renal dynamic imaging was performed and the image was processed according to standard procedure (Gates' method) to obtain GFR. 3 mL of blood was withdrawn 2 h and 4 h postinjection, respectively, and radioactivity of 1mL plasma was measured. GFR was calculated by the formula of two-sample method. The correlation of GFRs measured by renal dynamic imaging and by two-sample method was analyzed using regression analysis. The correlations of GFRs determined by the two methods with urea and creatinine were also measured. RESULTS: The GFR measured by renal dynamic imaging was slightly lower than that measured by two-sample method. Excellent correlation was obtained by two methods with r= 0.881 5 and P<0.01. The linear regression equation was GFR (renal dynamic imaging method)=0.661 4GFR (two-sample method) +21.89. The related lines of GFRs measured by the two methods with urea or creatinine were similar, which indicated the two methods were similar in identifying the changes in renal function. GFRs measured by the two methods showed good agreement for most of patients except three patients who were too thin or too fat. CONCLUSION: Generally, GFR obtained by renal dynamic imaging is reliable for identifying the changes in renal function and correlated well with GFR obtained by two-sample method. But great error may be obtained with specific individuals, such as too thin or too fat subjects.

Diagnostic accuracy of various glomerular filtration rates estimating equations in patients with chronic kidney disease and diabetes.

BACKGROUND: The equations for estimating glomerular filtration rate (GFR) based on creatinine have been found to have limitations and have not been generalizable across all populations. Equations based on cystatin C provide an alternative method to estimate GFR. Whether the equation based on cystatin C alone or combined creatinine would improve GFR estimates has not been validated among Chinese patients with chronic kidney disease (CKD) and diabetes. The aim of this study was to compare the performance of the modification of diet in renal disease (MDRD) equation based on creatinine with the five cystatin C-based formulae for estimation of GFR in patients with CKD and diabetes. METHODS: A total of 166 patients with CKD and 91 patients with type 2 diabetes were enrolled in this study. Cystatin C was measured by using the particle-enhanced immunonephelometric method and estimated formulae proposed by five different investigator teams (Stevens, Ma, Rule, Macisaac and Perkins). The plasma clearance of (99m)Tc-DTPA was determined as measured GFR (mGFR). RESULTS: For CKD patients, the bias and accuracy for the Ma and Macisaac equations were superior compared with the MDRD, and the mean results for the Ma formula were closer to mGFR than the other equations in CKD stages 2 - 5. The differences between Macisaac and mGFR in CKD stages 2 - 4 were significantly less than those in CKD stage 1 or 5. Stevens and Rule's formulae revealed a similar bias and accuracy compared with the MDRD equation. The MDRD formula had a higher accuracy in CKD stages 3 - 5 as compared with the results in other stages. For diabetic patients, the mean results between Macisaac and mGFR were closer than those of other equations in mGFR >or= 90 mlxmin(-1)x1.73 m(-2) stage. In GFR 60 - 89 mlxmin(-1)x1.73 m(-2) stage, the MDRD formula showed the smallest difference compared with other equations. All equations overestimated GFR in the cases with GFR < 60 mlxmin(-1)x1.73 m(-2) stages. The MDRD formula had a greater accuracy within 50% of mGFR than the equations based on cystatin C in diabetic patients. Perkins formula showed a large positive bias and low accuracy, therefore it may not be suitable for assessing GFR in patients with CKD and diabetes. CONCLUSIONS: The formulae for estimating GFR based on cystatin C or creatinine have different trends and accuracies in patients with CKD and diabetes, especially in patients with various GFR levels. The equations based on cystatin C provide less accurate results than MDRD formulae, at least in the diabetic patients. Therefore, whether the formulae based on cystatin C are superior to MDRD formula requires further investigation in large diverse populations.

Determination of reference intervals for creatinine and evaluation of creatinine-based estimating equation for Chinese patients with chronic kidney disease.

BACKGROUND: Several equations have been developed to estimate glomerular filtration rate (GFR). The aim of this study was to evaluate the performance of the three equations derived from Modification of Diet in Renal Disease (MDRD) formula: a-MDRD (original simplified), c-MDRD (modified with the Chinese coefficient), and j-MDRD (modified with the Japanese coefficient) in Chinese patients with chronic kidney disease (CKD). We also established the serum creatinine (Scr) reference intervals for Chinese healthy population. METHOD: A total of 1132 healthy individuals and 283 CKD patients were enrolled in this study. Scr was measured by Jaffe kinetic method. RESULTS: The sex-related Scr reference intervals were 71-104 micromol/l for males and 59-85 micromol/l for females. The c-MDRD equation overestimated reference GFR (rGFR) in CKD at stages 2, 3 and 4, but yielded lower bias over wide range of GFR. However, j-MDRD and a-MDRD resulted in a considerable bias. The j-MDRD equation was significantly lower than rGFR over wide range of GFR. a-MDRD and c-MDRD revealed similar accuracy, whereas j-MDRD produced lower accuracy than a-MDRD. CONCLUSION: No racial differences in the Scr reference intervals were observed. The modified MDRD formulas based on data from Asian population do not significantly improve the accuracy and bias, as compared those of the original MDRD. Therefore, whether the original MDRD for GFR estimation needs to be modified by an ethnic factor requires further investigation and validation.