"Very early" intrahepatic cholangiocarcinoma (≤ 2.0 cm): MRI manifestation and prognostic potential.

AIMS: To explore the MRI characteristics and clinical outcome of the "very early" intrahepatic cholangiocarcinoma (iCCA) ≤2.0cm. MATERIALS AND METHODS: Totally 213 pathologically confirmed iCCAs (44 ≤ 2.0cm and 169 of 2.0-5.0cm) from two institutes were included. Forty-four matching non-iCCA malignancies ≤2.0cm were also enrolled. Recurrence-free survival (RFS) was estimated and compared between iCCAs ≤2.0cm and 2.0-5.0cm. MRI features were analyzed and compared between iCCAs ≤2.0cm and 2.0-5.0cm, as well as between iCCAs ≤2.0cm and non-iCCAs ≤2.0cm. Univariate and multivariate regression analyses were performed to identify independent imaging features for discrimination. An MRI-based diagnostic model for iCCA ≤2.0cm was constructed by incorporating the independent imaging features. RESULTS: ICCAs ≤2.0cm had a significantly longer RFS than those of 2.0-5.0cm (log rank P=0.014). Imaging features of homogeneous signal (odds ratio (OR) = 6.677, P<0.001) and lack of vessel invasion (OR=7.56, P<0.001) were more frequently displayed in iCCAs ≤2.0cm compared to iCCAs of 2.0-5.0cm independently. In the small lesions ≤2.0cm, imaging features of progressive or persistent enhancement pattern (OR=27.78, P=0.002) and rim diffusion restriction (OR=5.70, P=0.027) were independent imaging features suggestive of iCCA over non-iCCA malignancy; their combination yielded an area under the curve value of 0.824, with a sensitivity of 97.73%. CONCLUSION: The "very early" iCCA ≤2.0cm was associated with a favorable outcome after surgery, it displayed different and relatively atypical imaging manifestations compared with those of 2.0-5.0cm. Furthermore, in the small lesions ≤ 2.0cm, MRI can be served as a useful non-invasive diagnostic tool for iCCA in clinical screening with high sensitivity.

Improved small vessel visibility in diabetic foot arteriography using dual-energy CT.

AIM: To test the feasibility and performance of dual-energy computed tomography (DECT) in foot arteriography of diabetic patients, where contrast medium is largely reduced within the small vessels. MATERIALS AND METHODS: A total of 50 diabetic patients were enrolled prospectively, where DECT was acquired immediately after the CT angiography (CTA, group A) of the lower extremity. Two images were derived from the DECT data, one optimal virtual monochromatic image (VMI, group B) and one fusion image (group C), both of which were compared against the CTA image for visualising the foot arteries. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were evaluated. The arterial course and contrast were graded each using a five-point scale. The clarity of small vessel depiction was quantified by comparing the number of plantar metatarsal arteries found in the maximum intensity projection image. RESULTS: The median CNRs and SNRs obtained in group B were approximately 45% and 20% higher than those in groups A and C, respectively (p<0.05). Group B also received higher subjective scores on the posterior tibial artery and the foot arteries (all >3) than groups A and C. The number of visible branches of the plantar metatarsal arteries was found to be substantially higher (p<0.05) in group B (median=6) than in groups A (median=2) and C (median=4). CONCLUSION: DECT was found to be superior to conventional CTA in foot arteriography, and beyond the lower extremity, it might be a general favourable solution for imaging regions with small vessels and reduced contrast medium.

Vesical Imaging-Reporting and Data System (VI-RADS) as a grouping imaging biomarker combined with a decision-tree mode to preoperatively predict the pathological grade of bladder cancer.

AIM: To investigate whether the Vesical Imaging-Reporting and Data System (VI-RADS) could be used to develop a new non-invasive preoperative grade-prediction system to partially predict high-grade bladder cancer (HG-BC). MATERIALS AND METHODS: The present study enrolled 89 primary BC patients prospectively from March 2022 to June 2023. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of VI-RADS for predicting HG-BC and muscle-invasive bladder cancer (MIBC) in the entire group. In the low VI-RADS (≤2) group, the decision tree-based method was used to obtain significant predictors and construct the decision-tree model (DT model). The performance of the DT model and low VI-RADS scores for predicting HG-BC was determined using ROC, calibration, and decision curve analyses. RESULTS: At a cut-off of ≥3, the specificity and positive predictive value of VI-RADS for predicting HG-BC in the entire group was 100%, and the area under the ROC curve (AUC) was 0.697. Among 65 patients with low VI-RADS scores, the DT model showed an AUC of 0.884 in predicting HG-BC compared to 0.506 for low VI-RADS scores. Calibration and decision curve analyses showed that the DT model performed better than the low VI-RADS scores. CONCLUSION: Most VI-RADS scores ≥3 correspond to HG-BCs. VI-RADS could be used as a grouping imaging biomarker for a pathological grade-prediction procedure, which in combination with the DT model for low VI-RADS (≤2) populations, would provide a potential preoperative non-invasive method of predicting HG-BC.

[Clinicopathological study of epithelioid and spindle cell rhabdomysarcoma with EWSR1/FUS-TFCP2 fusion].

Objective: To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion. Methods: The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed. Results: There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis. Conclusions: Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

[MRI manifestations of 40 cases with the hepatic epithelioid hemangioendothelioma classification based on the morphology and size].

Objective: To explore the MRI characteristics of the hepatic epithelioid hemangioendothelioma (HEHE) classification according to morphology and size. Methods: The clinical, pathological, and MRI imaging data of 40 cases with HEHE confirmed pathologically from December 2009 to September 2021 were retrospectively analyzed. A paired sample t-test was used for comparison between the two groups. Results: There were 40 cases (5 solitary, 24 multifocal, 9 local fusion, and 2 diffuse fusion) and 214 lesions (163 nodules, 31 masses, and 20 fusion foci). The most common features of lesions were subcapsular growth and capsular depression. The signal intensity of lesions ≤1cm was usually uniform with whole or ring enhancement. Nodules and mass-like lesions ≥1cm on a T1-weighted image had slightly reduced signal intensity or manifested as a halo sign. Target signs on a T2-weighted image were characterized by: target or centripetal enhancement; fusion-type lesions; irregular growth and hepatic capsular retraction, with ring or target-like enhancement in the early stage of fusion and patchy irregular enhancement in the late stage; blood vessels traversing or accompanied by malformed blood vessels; focal bleeding; an increasing proportion of extrahepatic metastases and abnormal liver function with the type of classified manifestation; primarily portal vein branches traversing; and reduced overall intralesional bleeding rate (17%). Lollipop signs were presented in 19 cases, with a high expression rate in mass-type lesions (42%). The fusion lesions were expressed, but the morphological manifestation was atypical. The diffusion-weighted imaging mostly showed high signal or target-like high signal. An average apparent diffusion coefficient of lesions was (1.56±0.36) ×10(-3)mm(2)/s, which was statistically significantly different compared with that of adjacent normal liver parenchyma (t=8.28, P<0.001). Conclusion: The MRI manifestations for the HEHE classification are closely related to the morphology and size of the lesions and have certain differences and characteristics that are helpful for the diagnosis of the disease when combined with clinical and laboratory examinations.

[Magnetic resonance imaging features and classification of intraductal papillary neoplasm of the bile duct].

Objective: To explore the magnetic resonance imaging (MRI) features and classification of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Data from 90 patients with intraductal papillary neoplasm of the bile duct confirmed pathologically between June 2010 and January 2023 were retrospectively analyzed. The image analysis included the shape and location of the tumor, whether bile ducts had dilatation and the degree of dilation, whether there was a history of liver disease, whether there was a history of schistosomiasis, whether there was cancerous transformation, whether there were concurrent bile duct stones, whether there was hepatic lobe atrophy, whether there was hilar or abdominal lymph node enlargement, whether there was invasion of the bile duct wall, whether there was invasion of surrounding blood vessels, whether the tumor appears on T1-and T2 weighted imaging (T(1)WI and T(2)WI), whether the diffusion was limited, whether there was concurrent bleeding, enhancement rate, and whether there was abdominal fluid accumulation. Intraductal papillary neoplasms of the bile duct were divided into four types according to the morphological classification standards: type I (local bile duct dilation), type II (cystic), type III (free tumor), and type IV (dilated bile duct). The differences in the clinical and MRI features of the four groups of lesions were analyzed. Statistical analysis was performed with a t-test, an analysis of variance, and an χ(2)-test according to the different data. Results: Among the 90 cases with hepatic IPNB, there were 31 cases of type I, 15 cases of type II, 16 cases of type III, and 28 cases of type IV, 41 cases of liver left lobe, 11 cases of right and left lobe liver span, 7 cases of liver right lobes, 2 cases of liver caudate lobe, and 13 cases of hepatic hilar. There were statistically significant differences between the four groups (P < 0.05) in terms of age, clinical symptoms, direct bilirubin, γ-glutamyltransferase, whether they were cancerous, whether they were combined with bile duct stones, whether the liver lobes were atrophying, whether there was limited diffusion, intrahepatic bile duct diameter, and common bile duct diameter. However, there were no statistically significant differences among the four groups in gender, location, carbohydrate antigen 19-9, history of liver disease, history of schistosomiasis, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, total bilirubin, whether hemorrhage was associated, lesion enhancement rate, whether the hilar/retroperitoneal lymph node was enlarged, whether the bile duct wall was invaded, whether blood vessels were invaded, and whether abdominal fluid was accumulated (P > 0.05). Conclusion: MRI manifestations have certain features for different types of intraductal papillary neoplasm of the bile duct tumors; hence, MRI aids in the diagnosis and differential diagnosis of this disease.

Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.

Quantitative image features of gadoxetic acid-enhanced MRI for predicting glypican-3 expression of small hepatocellular carcinoma ≤3 cm.

AIM: To explore the value of quantitative image features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) for predicting Gglypican-3 (GPC3) expression of single hepatocellular carcinoma (HCC) ≤3 cm. MATERIALS AND METHODS: One hundred and forty-nine patients with histopathologically confirmed HCC were included retrospectively. Quantitative image features and clinicopathological parameters were analysed. The significant predictors for GPC3 expression were identified using multivariate logistic regression analyses. Nomograms were constructed from the prediction model and the progression-free survival (PFS) rate was evaluated by the Kaplan-Meier method. RESULTS: The tumour-to-liver signal intensity (SI) ratio on the hepatobiliary phase (HBP; odds ratio [OR] = 0.004; p=0.001), serum alpha-fetoprotein (AFP) > 20 ng/ml (OR=6.175; p<0.001), and non-smooth tumour margin (OR=4.866; p=0.002) were independent significant factors for GPC3 expression. When the three factors were combined, the diagnostic specificity was 97.7% (42/43). The nomogram based on the predictive model performed satisfactorily (C-index: 0.852). Kaplan-Meier curves showed that patients with GPC3-positive HCCs have lower PFS rates than patients with GPC3-negative HCCs (Log-rank test, p=0.006). CONCLUSION: The tumour-to-liver SI ratio on the HBP combined with serum AFP >20 ng/ml and non-smooth tumour margin are potential predictive factors for GPC3 expression of small HCC ≤3cm. GPC3 expression is correlated with a poor prognosis in HCC patients.

Development and multicenter validation of a novel radiomics-based model for identifying eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Reliable noninvasive methods are needed to identify endotypes of chronic rhinosinusitis with nasal polyps (CRSwNP) to facilitate personalized therapy. Previous computed tomography (CT) scoring system has limited and inconsistent performance in identifying eosinophilic CRSwNP. We aimed to develop and validate a radiomics-based model to identify eosinophilic CRSwNP. METHODS: Surgical patients with CRSwNP were recruited from Tongji Hospital and randomly divided into training (n = 232) and internal validation cohort (n = 61). Patients from two additional hospitals served as external validation cohort-1 (n = 84) and cohort-2 (n = 54), respectively. Data were collected from October 2013 to May 2021. Eosinophilic CRSwNP was determined by histological criterion. The least absolute shrinkage and selection operator and the logistic regression (LR) algorithm were used to develop a radiomics model. Univariate and multivariate LR were employed to build models based on CT scores, clinical characteristics, and the combination of radiological and clinical characteristics. Model performance was evaluated by assessing discrimination, calibration, and clinical utility. RESULTS: The radiomics model based on 10 radiomic features achieved an area under the curve (AUC) of 0.815 in the training cohort, significantly better than the CT score model based on ethmoid-to-maxillary sinus score ratio with an AUC of 0.655. The combination of radiomic features and blood eosinophil count had a further improved performance, achieving an AUC of 0.903. The performance of these models was confirmed in all validation cohorts with satisfying predictive calibration and clinical application value. CONCLUSIONS: A CT radiomics-based model is promising to identify eosinophilic CRSwNP. This radiomics-based method may provide novel insights in solving other clinical concerns, such as guiding personalized treatment and predicting prognosis in patients with CRSwNP.

[The optimal examination duration for the detection of epileptiform discharge in outpatient video-electroencephalography].

Objective: To determine the optimal examination duration by evaluating the detection rate of epileptiform discharges (EDs) with different examination duration of video-electroencephalography (EEG) in outpatients. Methods: Patients with EDs who underwent 4-hour EEG examination from Xuanwu Hospital, Capital Medical University from October 2020 to November 2021 were retrospectively enrolled, and the detection rates of EDs were calculated with examination duration of 0-0.5 h, 0-1 h, 0-2 h, 0-3 h, and 0-4 h (group A, B, C, D and E), respectively. For each patient, EDs in each hour (group H1, group H2, group H3, group H4) were counted, and the standardized amount of EDs was calculated. For each patient, EDs in wakefulness, drowsiness, non-rapid eye movement-Ⅰ (NREM-Ⅰ), NREM-Ⅱ and NREM-Ⅲ were counted, and the standardized amount of EDs in each state was calculated. Meanwhile, the sleep duration per hour of each patient was also counted (group H1', group H2', group H3', group H4'). The Wilcoxon paired test was used for intergroup comparison to determine the optimal examination duration. Results: A total of 80 patients were enrolled, and aged [M(Q1, Q3)]31 (21, 39) years (range: 5-68 years). There were 38 males and 42 females. The detection rate of EDs was 42.5% (34/80) in group A, 81.3% (65/80) in group B, and 100.0% (80/80) in group C, group D and group E, respectively. The standardized amount of EDs of H1, H2, H3 and H4 was 24.8% (7.8%, 44.2%), 41.5% (25.9%, 63.3%), 15.1% (1.3%, 27.8%) and 1.3% (0, 14.5%), respectively. The standardized amount of EDs of H2 was significantly higher than that of H1, H3 and H4 (all P<0.05). The standardized amount of EDs in wakefulness, drowsiness, NREM-Ⅰ, NREM-Ⅱ and NREM-Ⅲ were 9.6% (0, 28.2%), 3.6% (0, 16.9%), 3.3% (0, 11.8%), 47.3% (21.9%, 72.5%) and 0 (0, 11.5%), respectively. The standardized amount of EDs in NREM-Ⅱ was significantly higher than that in wakefulness, drowsiness, NREM-Ⅰ and NREM-Ⅲ (all P<0.05). The sleep duration in the group of the H1', H2', H3' and H4' was 13.6 (2.5, 23.6), 35.8 (16.5, 54.2), 14.5(0, 34.7) and 0 (0, 14.6) minutes, respectively. The sleep duration in the group of the H2' group was significantly longer than that in the group of H1', H3' and H4' (all P<0.05). Conclusion: The study recommends 2 hours video-EEG in outpatients, which not only ensures the detection rate of EDs, but also facilitates patient cooperation and optimizes the allocation of medical resources.

[Analysis of MRI features of hepatocyte nuclear factor 1α-inactivated hepatocellular adenoma].

Objective: To investigate the MRI imaging features of hepatocyte nuclear factor 1α- inactivated hepatocellular adenoma (H-HCA). Methods: Clinical data and MRI images of 19 H-HCA cases who were pathologically confirmed at Zhongshan Hospital Affiliated to Fudan University between August 2014 and July 2020 were retrospectively analyzed. Among them, there were 15 females and 4 males, aged 16-47 (32± 7) years old. Tumor number, location, shape, size, boundary, MRI plain scan signal intensity, dynamic enhancement features of each phase, presence or absence of intratumoral fat content, pseudocapsule, and others were analyzed. The differences in apparent diffusion coefficient (ADC) values between the lesion and the surrounding normal liver parenchyma were compared for statistical significance. t-test was used for statistical analysis. Results: There were a total of 24 lesions in 19 cases. 14 cases had solitary lesions, and five cases had multiple lesions. 15 and nine lesions were located in the right and left lobes of the liver, respectively. 20 lesions were round or quasi-round, and four were irregular or lobulated. The tumor's maximal diameter was 0.6-8.6 (3.5 ± 2.4) cm. T(1)-weighted image (WI) showed hyperintense to iso-intense signals in 20 lesions and hypointense signals in four. T(2)WI showed iso-to-slightly high signal intensity in 16 lesions, with two hyperintense and six hypointense signals. Diffusion-weighted image (DWI) revealed hyperintense to iso-intense signals. Lesions mean ADC value was (1.289 ± 0.222)×10(-3) mm(2)/s, while the adjacent normal liver parenchyma's mean ADC value was (1.307 ± 0.236)×10(-3) mm(2)/s, with no statistically significant difference between the two (P > 0.05). During the arterial phase, 15 of the 18 lesions that underwent dynamic contrast-enhanced scanning with gadoxetate disodium (Gd-DTPA) were mildly to moderately enhanced and three were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the delayed phase showed a hypointense signal. During the arterial phase, two of the six lesions scanned by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid ((Gd-EOB-DTPA) dynamic enhancement were mildly to moderately enhanced, while four were strongly enhanced. The portal and hepatic venous phases had no continuous enhancement, while the transition and hepatobiliary-specific phases showed hypointense signals. Intracellular steatosis occurred in 21 lesions, of which 19 were diffuse steatosis and 16 formed pseudocapsules in the delayed phase. Conclusion: H-HCA often occurs in young females as solitary lesions and has certain MRI features. T1WI anti-phase diffuse signal reduction and post-enhanced hypovascular withdrawal enhancement patterns can aid in accurately diagnosing the disease condition.

[C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery].

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above the Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortium.

OBJECTIVES: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. METHODS: We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. RESULTS: 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (ß = 0.23, 95% CI: 0.09, 0.38) and synovitis (ß = 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (ß = 0.37, 95% CI: 0.21, 0.53); synovitis (ß = 0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (ß = 0.051, 95% CI: 0.01, 0.09) and over 24 months (ß = 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. CONCLUSION: Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.

A bibliometric analysis of primary ovarian insufficiency from 2010 to 2020.

OBJECTIVE: This study aimed to carry out a bibliometric analysis of primary ovarian insufficiency (POI) from 2010 to 2020 and to reveal the research status and hotspots in the future. METHOD: A total of 3087 articles and reviews related to POI published from 2010 to 2020 retrieved from the Web of Science Core Collection were used for bibliometric analysis. CiteSpace and VOSviewer were adopted to analyze countries and regions, organizations, authors, journals, keywords and co-cited references. RESULTS: The number of publications about POI increased year by year. The USA produced the largest number of publications and the most influence in this field. The main research directions of POI can be roughly divided into four aspects according to the analysis of keywords and co-cited references: genetic research of POI; stem cell therapy for patients with POI; prediction of ovarian function; and fertility preservation of cancer patients. Genetic research and stem cell therapy may become research hotspots in the future. CONCLUSION: This study might be the first bibliometric study to analyze publications of POI from multiple indicators, in order to provide new opinions for the research trends and possible hotspots of POI.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

[MRI features of lymphoepithelioma-like intrahepatic cholangiocarcinoma].

Objective: To investigate the MRI manifestations of lymphoepithelioma-like intrahep cholangiocarcinoma (LEL-ICC). Methods: MR images of 26 cases with LEL-ICC confirmed pathologically at Zhongshan Hospital Affiliated with Fudan University between March 2011 and March 2021 were retrospectively analyzed. The number, location, size, morphology, edges of lesions, non-scan signal intensity, cystic necrosis, enhancement mode, peak, and capsule, vascular invasion, lymph node metastasis, and other MR images were included for analysis. The apparent diffusion coefficient (ADC) value of the lesion and the surrounding normal liver parenchyma were measured. A paired-sample t-test was used to statistically analyze the measurement data. Results: All 26 cases of LEL-ICC had solitary lesions. Mass-type LEL-ICC was the most common [n=23, lesion size (4.02±2.32) cm] with distribution along the bile duct [n=3, lesion size (7.23±1.40 cm)]. Among the 23 lesions of mass type LEL-ICC, most of the lesions were close to the liver capsule (n=20), round (n=22), clearly bordered (n=13), and cystic necrosis (n=22). In the three lesions of LEL-ICC distributed along the bile duct, most of them were close to the liver capsule (n=2), irregular (n=3), blurred edges (n=3), and cystic necrosis (n=3). All 26 lesions showed a low/slightly low signal on T1WI, a high/slightly high signal on T2WI, and a slightly high or high signal on DWI. Three lesions showed fast-in and fast-out enhancement modes, and 23 lesions showed continuous enhancement. Twenty-five lesions showed peak enhancement in the arterial phase, and one lesion appeared in the delayed phase. The ADC value of 26 lesions and adjacent normal liver parenchyma was (1.112±0.274)×10-3 mm2/s and (1.482±0.346)×10-3 mm2/s, respectively, and the both had a statistically significant difference (P<0.05). Conclusion: Certain manifestations of LEL-ICC in magnetic resonance imaging are advantageous for diagnosis and differential diagnosis.

[Safety and feasibility of stereotactic radiation therapy on porcine ventricular septum: a preliminary study].

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.

The effectiveness of educational programmes in promoting sun protection among children under the age of 18: a systematic review and meta-analysis.

Childhood ultraviolet radiation exposure has a strong connection to the development of skin cancer in later life. Therefore, there have been numerous sun protection educational programmes targeted to this age group. However, the association between these have not been well established. This systematic review aims to summarize the evidence on, and assess, the effectiveness of educational programmes in improving sun protection among children under age-18. The protocol was prospectively registered in the PROSPERO database (CRD42020178264). Per PRISMA guidelines, bibliographic databases CENTRAL, OVID (EMBASE, MEDLINE, PsycINFO), LILACS, trial registries, grey literature and other sources were systematically searched for randomized controlled and clinical controlled trials published between database inception to 9 June 2020. Dual independent review of abstracts and full texts was performed. Eligible studies were assessed for methodological quality using the Cochrane risk-of-bias tool. The primary outcome was postintervention scores [standardized mean difference (SMD)] for sun protection (i) knowledge (ii) attitudes and beliefs (iii) behavioural intentions and behaviours. Sidik-Jonkman random effects meta-analysis, sensitivity and subgroup analyses were performed for specific outcomes (sunscreen and sun-safe hat use) which were sufficiently reported. 1350 publications were identified and 24 eligible trials, conducted across 8 different countries, with sufficient aggregate data were included. Small-to-moderate effects of educational programmes were observed across all sun protection outcomes of interest, but negligible effect sizes were demonstrated when specific outcomes were meta-analysed - sunscreen use, SMD 0.18 (95% CI 0.07-0.29; n = 8) and sun-safe hat use, SMD 0.08 (95% CI, 0.00-0.16; n = 6). A promising approach in the future may be to consider targeting children in secondary education with a digitally delivered interactive intervention. Current evidence, however, is insufficient to assess the effects of potential moderators and change in sun protection outcomes is likely not one-size-fits-all. Further research is warranted to direct intervention design and public policy.

[Related factors for hyperkalemia and its recurrence in maintenance hemodialysis patients].

Objective: To investigate the prevalence of hyperkalemia and recurrent hyperkalemia in maintenance hemodialysis patients, and identify the related factors. Methods: The general information and clinical data of maintenance hemodialysis patients in the hemodialysis center of the First Affiliated Hospital of Nanjing Medical University from January to December 2020 were collected. According to the level of serum potassium, the patients were divided into normokalemia group and hyperkalemia group. Patients in the hyperkalemia group were further divided into single hyperkalemia group and recurrent hyperkalemia group according to the number of occurrences of hyperkalemia. Then, the prevalence of different serum potassium abnormalities and the related factors were explored. Results: Among the 352 patients included in the final analysis, 129 cases (36.6%) were in the normokalemia group [mean age: (62±15) years, 99 males] and 223 cases (63.4%) were in the hyperkalemia group [mean age: (60±14) years, 153 males]. Multivariate logistic regression analysis demonstrated that, compared with the normokalemia group, night-time dialysis (OR=4.012, 95%CI: 1.519-10.601, P=0.005), concurrent diabetes (OR=1.947, 95%CI: 1.148-3.304, P=0.013) and the number of serum potassium tested before hemodialysis (OR=1.561, 95%CI:1.292-1.885, P<0.001) were independent risk factors for hyperkalemia. Among 223 patients with hyperkalemia, 78 cases (35.0%) were in single hyperkalemia group and 145 cases (65.0%) were in recurrent hyperkalemia group. Multivariate logistic regression analysis demonstrated that, serum calcium (OR=21.885, 95%CI: 3.740-128.077, P=0.001), peak value of serum potassium before hemodialysis (OR=63.157, 95%CI: 25.265-157.876, P<0.001) and the number of serum potassium tested before hemodialysis (OR=1.814, 95%CI: 1.378-2.388, P<0.001) were the independent risk factors for the recurrence of hyperkalemia. Conclusions: The prevalence of hyperkalemia is high in maintenance hemodialysis patients, especially in those with diabetes or night-time dialysis. It is necessary to monitor serum potassium regularly. In addition, high serum calcium and peak value of serum potassium before hemodialysis are related factors for recurrent hyperkalemia.

[Association of urinary sodium excretion with fluid overload in patients with chronic kidney disease].

Objective: To investigate the relationship between urinary sodium excretion and fluid overload (FO) in non-dialysis patients with chronic kidney disease (CKD). Methods: Patients with CKD stage 1-4 who underwent bioelectrical impedance (BIA) in the Department of Nephrology, Jiangsu Province Hospital from December 2019 to January 2021 were recruited. All enrolled patients were categorized into two groups according to whether or not they develop FO. Further, clinical parameters were compared between the two groups. Spearman correlation analysis was used to investigate the association between over hydration/extracellular water (OH/ECW) and clinical characteristics. Multivariate logistic regression analysis was performed to evaluate the relationship between urinary sodium excretion and FO (FO was defined as OH/ECW≥7%). Results: A total of 385 patients with CKD stage 1-4 were finally included in the study, with a mean age of (46±15) years. There were 216 male cases (56.1%), and 150 cases (39.0%) existed FO. Spearman correlation analysis indicated that OH/ECW positively correlated with urinary sodium excretion (r=0.147, P=0.004), urinary protein excretion (r=0.555, P<0.001) and systolic blood pressure (r=0.241, P<0.001), but inversely related to estimated glomerular filtration rate (eGFR) (r=-0.111, P=0.030) and serum albumin (r=-0.659, P<0.001). After adjusting for confounding factors including age, systolic blood pressure, diabetes, urinary protein excretion, serum albumin, serum sodium, serum chlorine, urinary calcium excretion, urinary phosphorus excretion and use of diuretics, multivariate logistic regression analysis demonstrated that higher level of urinary sodium excretion was associated with increased risk of FO in patients with CKD (OR=1.005, 95%CI: 1.000-1.011, P=0.048). Conclusion: High urinary sodium excretion is independently associated with fluid FO in non-dialysis patients with CKD.