Heterogeneity of Radiological Progression Patterns and Association with Outcomes in Patients with Metastatic Prostate Cancer.

BACKGROUND: With an increasing number of clinical trials using radiographic progression-free survival (rPFS) instead of overall survival as the primary study endpoint, the heterogeneity of different radiological progression patterns in rPFS and postprogression survival (PPS) remains unclear. OBJECTIVE: Herein, we investigate the proportion of various radiological progression patterns in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC), and further explore the differences in rPFS and PPS between patients exhibiting single- or multicategory progression patterns. DESIGN, SETTING, AND PARTICIPANTS: This post hoc, retrospective secondary analysis was based on individual patient data from LATITUDE (phase 3 randomized mHSPC study) and COU-AA-302 (phase 3 randomized mCRPC study). Patients with complete imaging follow-up data and radiological progression were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The rPFS and PPS in LATITUDE and COU-AA-302 were evaluated. The proportion of patients exhibiting each progression pattern was calculated, and a survival analysis was conducted using the Kaplan-Meier method. RESULTS AND LIMITATIONS: Of the 489 mHSPC patients studied, 366 experienced single-category progression, while the remaining 123 patients (25.2%) exhibited simultaneous occurrence of different progressive events (multicategory radiological progression). Of the 534 mCRPC patients studied, 390 experienced single-category progression, while the remaining 144 patients (27.0%) experienced multicategory progressive events. Among mCRPC patients, the rPFS of bone progression was the shortest. In contrast, among mHSPC patients, the rPFS of target lesion enlargement is the shortest, followed by bone progression. Notably, patients experiencing a single-category progression pattern displayed comparable rPFS to but significantly longer PPS than those experiencing multicategory progression patterns (PPS mHSPC cohort: 21.5 vs 6.9 mo, p < 0.0001; mCRPC cohort: 23.6 vs 15.7 mo, p < 0.0001). The study is limited by its hypothesis-generating nature. Therefore, the observed phenomena in our research necessitate validation through future prospective studies. CONCLUSIONS: Patients who experience multicategory radiological progression represent a significant proportion, accounting for approximately 25% of all men with mHSPC or mCRPC. Patients with multicategory radiological progression patterns had similar rPFS to but significantly shorter PPS than those experiencing single-category progression patterns. In future clinical trials and clinical practice, radiological progression patterns should be recognized as a crucial determinant of prognosis, while also serving as the stratification or inclusion criteria for second-line treatment clinical trials. PATIENT SUMMARY: In this study, we observed that among men with metastatic prostate cancer, those who experienced two or more radiological events during a single visit had a worse prognosis than those who experienced isolated radiological events.

Hepatocellular Carcinoma with Radiological Progression: Lenvatinib Plus PD-1 Inhibitor Combined with Microwave Ablation and Synchronous Transarterial Chemoembolization.

Purpose: To determine the clinical outcomes of lenvatinib plus PD-1 inhibitor combined with microwave ablation (MWA) and synchronous transarterial chemoembolization (TACE) in patients with progressive hepatocellular carcinoma (pHCC). Materials and Methods: This retrospective study enrolled pHCC patients who underwent lenvatinib plus PD-1 inhibitor combined with MWA and TACE (LP-MT) or lenvatinib combined with MWA and TACE (L-MT) from January 2019 to December 2022. Treatment-related adverse events (AEs) were recorded during the follow-up. Progression-free survival (PFS) and overall survival (OS) were the primary outcomes. The prognostic analyses for survival were performed using Cox proportional hazard regression model. Results: In total, 90 eligible patients with pHCC who received combination therapy were included in the study. Among them, 42 patients received LP-MT and 48 patients received L-MT. There were no significant differences in the baseline characteristics between the two groups. Patients who underwent lenvatinib plus PD-1 inhibitor combined with MWA and TACE had better PFS (median, 10.0 vs 7.4 months, P = 0.03) than those who underwent combination therapy without PD-1 inhibitor, although no significant difference was found in OS (median, 22.5 vs 20.0 months, P = 0.19) between the two groups. The disease control rate of LP-MT group was higher than that of L-MT group (88.1% vs 64.6%, P = 0.01), especially in patients with BCLC stage C (89.3% vs 70.0%, P = 0.03). Univariate and multivariate analyses indicated that treatment method and Child-Pugh class were independent prognostic factors for PFS. The AEs of LP-MT group were comparable and tolerable to those of L-MT group (Any grade, 78.6% vs 62.5%, P = 0.10; Grade 3, 23.8% vs 12.5%, P = 0.16). Conclusion: Lenvatinib plus PD-1 inhibitor may be slightly superior to lenvatinib alone when combined with local interventional therapy for progressive HCC, especially in patients with BCLC stage C.

Differences of molecular events driving pathological and radiological progression of lung adenocarcinoma.

BACKGROUND: Ground-glass opacity (GGO)-like lung adenocarcinoma (LUAD) has been detected increasingly in the clinic and its inert property and superior survival indicate unique biological characteristics. However, we do not know much about them, which hampers identification of key reasons for the inert property of GGO-like LUAD. METHODS: Using whole-exome sequencing and RNA sequencing, taking into account both radiological and pathological classifications of the same 197 patients concomitantly, we systematically interrogate genes driving the progression from GGO to solid nodule and potential reasons for the inertia of GGO. Using flow cytometry and IHC, we validated the abundance of immune cells and activity of cell proliferation. FINDINGS: Identifying the differences between GGO and solid nodule, we found adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA) and GGO-like LUAD exhibited lower TP53 mutation frequency and less active cell proliferation-related pathways than solid nodule in LUAD. Identifying the differences in GGO between AIS/MIA and LUAD, we noticed that EGFR mutation frequency and CNV load were significantly higher in LUAD than in AIS/MIA. Regulatory T cell was also higher in LUAD, while CD8+ T cell decreased from AIS/MIA to LUAD. Finally, we constructed a transcriptomic signature to quantify the development from GGO to solid nodule, which was an independent predictor of patients' prognosis in 11 external LUAD datasets. INTERPRETATION: Our results provide deeper insights into the indolent nature of GGO and provide a molecular basis for the treatment of GGO-like LUAD. FUNDING: This study was supported in part by the National Natural Science Foundation of China (32170657), the National Natural Science Foundation of China (82203037), and Shanghai Sailing Program (22YF1408900).

A radiological study of the natural history of diffuse idiopathic skeletal hyperostosis (DISH): a story of incomplete fusion.

Introduction: DISH is an ankylosing disease, when fractured can be challenging to manage. A retrospective radiological study was conducted to evaluate the natural history and radiological characteristics of DISH on Computed tomography (CT).Methods: Paired CT scans with DISH that are separated at least two years apart were used to perform the following radiological measurements: Degree of disc space fusion, Osteophyte and vertebral body linear attenuation coefficients (LAC), and Osteophyte axial area size and location.Results: 164 patients were analysed with a mean duration of 4.49 years between scans. 38.14% (442/1159) of disc spaces had at least partial calcification. Most osteophytes were right sided before becoming more circumferential over time. The average fusion score was 54.17. Most of the changes in fusion occurred in the upper and lower thoracic regions. The thoracic region when compared to the lumbar region had a greater proportion of its disc spaced being fully fused. Disc level osteophyte areas were larger than Body level osteophytes. Disc osteophytes size growth rate drops over time from 10.89mm2/year in Stage 1 to 3.56mm2/year in Stage 3. Stage 3 disc spaces (-11.01HU/year) was also found to have had a reduction in their LAC over time when compared to Stage 1 disc spaces (17.04HU/year). This change in osteophyte LAC was not mirrored in the change in vertebral body LAC. We predict that the age of onset and complete thoracolumbar ankylosis of DISH to be 17.96 years and 100.59 years, respectively.Conclusion: DISH ankylosis of the spine a slow process that starts in the mid to lower thoracic region before extending cranially and caudally. After the bridging osteophyte has fully formed, remodelling of the osteophyte occurs.

Reticulation Is a Risk Factor of Progressive Subpleural Nonfibrotic Interstitial Lung Abnormalities.

Rationale: Interstitial lung abnormalities (ILAs) are being increasingly identified in clinical practice. In particular, for subpleural nonfibrotic ILAs, the risk of progression over time and the risk factors for progressive behavior are still largely unknown. Objectives: To determine the age band prevalence of ILAs and the risk of radiological progression of subpleural nonfibrotic ILAs over time in a large health checkup population and to identify how reticulation contributes to the risk of radiological progression. Methods: On the basis of the ILAs definition by the Fleischner Society, low-dose chest computed tomography images from the community-dwelling population who have undergone health checkups were evaluated for ILAs. Multivariable logistic regression was used to assess the risk of radiological progression. Measurements and Main Results: Among 155,539 individuals, 3,300 (2.1%) were confirmed to have ILAs: the vast majority (81.7%) were defined as subpleural nonfibrotic ILAs. The prevalence of ILAs increased linearly with age (P for trend < 0.0001). Of 454 individuals with subpleural nonfibrotic ILAs, 198 (43.6%) had radiological progression over 4 years. The presence of reticulation on initial imaging was an independent predictor of radiological progression (odds ratio, 1.9; 95% confidence interval, 1.2-3.0; P = 0.0040). No difference in radiological progression was identified between subpleural nonfibrotic ILAs with extensive reticulation and subpleural fibrotic ILAs (73.0% vs. 68.8%; P = 0.7626). Conclusions: The prevalence of ILAs increases linearly with age. Nearly half of subpleural nonfibrotic ILAs progress radiologically over 4 years. The presence of reticulation is a risk factor for radiological progression. Subpleural nonfibrotic ILAs with extensive reticulation are likely to be a feature of subpleural fibrotic ILAs.

Performance of pre-transplant criteria in prediction of hepatocellular carcinoma progression and waitlist dropout.

BACKGROUND & AIM: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. METHODS: A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. RESULTS: HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). CONCLUSIONS: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

Low CD4 T cell count predicts radiological progression in severe and critically ill COVID-19 patients: a case control study.

BACKGROUND: Novel coronavirus disease (COVID-19) has spread globally and caused over 3 million deaths, posing great challenge on public health and medical systems. Limited data are available predictive factors for disease progression. We aim to assess clinical and radiological predictors for pulmonary aggravation in severe and critically ill COVID-19 patients. METHODS: Patients with confirmed COVID-19 in Renmin Hospital of Wuhan University, China, between Feb. 6th, 2020 and Feb. 21st, 2020 were retrospectively collected. Enrolled patients were divided into non-progression group and progression group based on initial and follow-up chest CTs. Clinical, laboratory, and radiological variables were analyzed. RESULTS: During the study period, 162 patients were identified and a total of 126 patients, including 97 (77.0%) severe cases and 29 (23.0%) critically ill cases were included in the final analysis. Median age was 66.0 (IQR, 56.0-71.3) years. Median time from onset to initial chest CT was 15.0 (IQR, 12.0-20.0) days and median interval to follow-up was 7.0 (IQR, 5.0-7.0) days. Compared with those who did not progress (n=111, 88.1%), patients in the progression group (n=15, 11.9%) had significantly higher percentage of peak body temperature >38 °C (P=0.002), lower platelet count (P=0.011), lower CD4 T cell count (P=0.002), lower CD8 count (P=0.011), higher creatine kinase level (P=0.002), and lower glomerular filtration rate (P=0.018). On both univariate and multivariable analysis, only CD4 T cell count <200/µL was significant (OR, 6.804; 95% CI, 1.450-31.934; P=0.015) for predicting pulmonary progression. CONCLUSIONS: Low CD4 T cell count predicts progression of pulmonary change in severe and critically ill patients with COVID-19.

Association of Baseline Cardiovascular Diseases with 5-Year Knee and Hip Osteoarthritis Progression in Non-Obese Patients: Data from the KHOALA Cohort.

We aimed to explore the relationship between comorbidities and the structural progression in symptomatic knee and/or hip osteoarthritis (OA) patients. We analyzed the 5-year outcome of non-obese participants (body mass index (BMI) < 30 kg/m2) from the KHOALA cohort having symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) ≥ 2). The primary endpoint was radiological progression, defined as ΔKL ≥ 1 of the target joint at 5 years. The secondary outcome was the incidence of total knee or hip replacement over 5 years. Dichotomous logistic regression models assessed the relationship of comorbidities with KL progression and joint replacement while controlling for gender, age and BMI. Data from 384 non-obese participants were analyzed, 151 with hip OA and 254 with knee OA. At 5 years, cardiovascular diseases (CVD) were significantly associated with the 5-year KL change in both knee (OR = 2.56 (1.14-5.78), p = 0.02) and hip OA (OR = 3.45 (1.06-11.17), p = 0.04). No significant relationship was found between any type of comorbidities and knee or hip arthroplasty. This 5-year association between CVD and radiological progression of knee and hip OA in non-obese participants argue for an integrated management of CVD in knee and hip OA non-obese patients.

Radiological Assessment and Outcome of Local Disease Progression after Neoadjuvant Chemotherapy in Children and Adolescents with Localized Osteosarcoma.

OBJECTIVE: We examined the interobserver reliability of local progressive disease (L-PD) determination using two major radiological response evaluation criteria systems (Response evaluation Criteria in Solid Tumors (RECIST) and the European and American Osteosarcoma Study (EURAMOS)) in patients diagnosed with localized osteosarcoma (OS). Additionally, we describe the outcomes of patients determined to experience L-PD. MATERIALS AND METHODS: Forty-seven patients diagnosed with localized OS between 2000 and 2012 at our institution were identified. Paired magnetic resonance imaging of the primary tumor from diagnosis and post-neoadjuvant chemotherapy were blindly assessed by two experienced radiologists and determined L-PD as per RECIST and EURAMOS radiological criteria. Interobserver reliability was measured using the kappa statistic (κ). The Kaplan Meier method and log-rank test was used to assess differences between groups. RESULTS: Of 47 patients (median age at diagnosis 12.9 years), 16 (34%) had L-PD (by RECIST or EURAMOS radiological definition). There was less agreement between the radiologists using EURAMOS radiological criteria for L-PD (80.9%, κ = 0.48) than with RECIST criteria (97.9%, κ = 0.87). Patients with radiologically defined L-PD had a 5-year progression-free survival (PFS) of 55.6%, compared to a 5 year-PFS of 82.7% in the group of patients without L-PD (n = 31) (Log rank p = 0.0185). CONCLUSIONS: The interobserver reliability of L-PD determination is higher using RECIST than EURAMOS. RECIST can be considered for response assessment in OS clinical trials. The presence of L-PD was associated with worse outcomes.

Effect of TNF-inhibitor therapy on spinal structural progression in ankylosing spondylitis patients: A systematic review and meta-analysis.

To review the effect of tumor necrosis factor-alpha inhibitor (TNFi) therapies on radiographic progression in ankylosing spondylitis (AS) patients as evaluated by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from inception to August 2019. All comparative and non-comparative studies that evaluated the clinical effectiveness of TNFi on radiographic progression as assessed by mSASSS change at a minimum follow-up of 1 year were included. The Newcastle-Ottawa Scale and Cochrane Collaboration Risk of Bias Tool were utilized to assess the methodological quality. Pooled analysis was performed for continuous and binomial variables where appropriate. Inter-rater reliability of mSASSS status and change scores were assessed with intra-class coefficients (ICC). Twenty-one studies were identified with a total of 4460 patients (mean age: 40.4 years [range 25.3-50 years]; 76% male; mean baseline mSASSS: 12.7 units [range 5.5-19.8 units]). All studies (3 randomized and 18 observational studies) were considered to have moderate-to-high methodological quality. The inter-rater reliability of mSASSS status and change scores from 14 of the 21 studies were excellent (ICC ranges, 0.91-0.99) and moderate-to-excellent (ICC ranges, 0.58-0.90), respectively. From the 21 studies, 11/21 (50%) demonstrated a delayed effect in mSASSS in AS patient administered TNFi. When stratifying these studies into those with ≤4 years of follow-up and >4 years follow-up, 3/11 (27%) and 8/10 (80%) studies respectively indicated a delayed effect of mSASSS with TNFi in AS patients. Pooling for meta-analysis from 3 studies (1159 patients) with study durations ranging 4-8 years, indicated that TNFi-treated patients had reduced odds of structural progression (odds ratio 0.81; 95% CI 0.68-0.96; P = .01; I2  = 0%). Mean rate of mSASSS change from 16 studies ranged from -0.15 to 7.3 mSASSS units for all AS patients. Meta-analysis indicated a numerical, but statistically non-significant, reduction in the rate of mSASSS change with TNFi treatment (7 studies [1438 patients]; mean difference, -0.24; 95% CI, -0.49-0.01; P = .06; I2  = 0%). This systematic review and meta-analysis indicated that >4 years of TNFi usage was associated with delayed structural progression by mSASSS. The narrative analysis of the data from 21 studies further confirmed that studies with >4 years of follow-up had delayed structural progression with TNFi use in AS patients. The systematic review also confirmed that mSASSS has good-to-excellent inter-rater reliability in AS.

Correlation of Prostate-specific Antigen Kinetics with Overall Survival and Radiological Progression-free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebos Added to Androgen Deprivation Therapy: Post Hoc Analysis of Phase 3 LATITUDE Study.

BACKGROUND: LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC). OBJECTIVE: To assess the correlation of prostate-specific antigen (PSA) kinetics with overall survival (OS) and radiological progression-free survival (rPFS). DESIGN, SETTING, AND PARTICIPANTS: A post hoc analysis of data from 597 men receiving AAP + ADT and 602 receiving PBO + ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The associations of PSA-related outcomes (rates of confirmed 50% [PSA50] and 90% [PSA90] decline from baseline PSA [Prostate Cancer Working Group 2 criteria], rates of PSA < 0.2 ng/ml, median nadir PSA, time to PSA nadir [TPN], and time to PSA progression [TPP] with long-term outcomes [OS and rPFS]) were evaluated. Hazard ratios (HRs) were estimated using Cox proportional hazard model. Correlations of TPP with coprimary endpoints rPFS and OS were evaluated using Kendall's tau (KT). RESULTS AND LIMITATIONS: AAP + ADT significantly delayed median TPP versus PBO + ADT (33.2 vs 7.4 mo; HR: 0.3, p <  0.001). TPP correlated with rPFS (KT = 0.921) and OS (KT = 0.666). In the AAP + ADT group, 91% had PSA50 and 79% had PSA90 responses (relative risk [RR]: 1.36 and 2.30, respectively; p <  0.001 for both comparisons vs PBO + ADT). Compared with nonresponders, PSA50 and PSA90 responders had reduced risk of death (RR: 0.44 and 0.12, respectively). At 6 mo, 40% receiving AAP + ADT and 6.5% receiving PBO + ADT achieved PSA ≤0.1 ng/ml, which was significantly associated with longer rPFS and OS. Median nadir PSA was 0.09 ng/ml with AAP + ADT versus 2.36 ng/ml with PBO + ADT. Median TPN (AAP + ADT, 6.4 mo; PBO + ADT, 3.8 mo) positively correlated with rPFS and OS. CONCLUSIONS: Superior PSA response dynamics with AAP + ADT versus ADT + PBO strongly correlated with long-term outcomes of rPFS and OS in high-risk mCSPC. PATIENT SUMMARY: We found that low prostate-specific antigen levels (≤0.1 ng/ml) after 6 mo may indicate a good long-term response to treatment. Our results need confirmation.

[Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis].

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

Prevalence of and Risk Factors for the Progression of Upper Cervical Lesions in Patients with Rheumatoid Arthritis.

We investigated the prevalence of and risk factors for the progression of upper cervical lesions (UCLs) in patients with rheumatoid arthritis (RA). A retrospective analysis of 49 patients with RA (4 males, 45 females) was conducted. The UCLs included atlanto-axial subluxation and vertical subluxation. We investigated the clinical factors including the Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and the modified Health Assessment Questionnaire-Disability Index as well as radiographic changes between the baseline (at May 2010 to April 2013) and final follow-up. Forty patients (81.6%) were classified as the non-progressive group, and the other 9 patients (18.4%) comprised the progressive group. The progressive group's final CRP values, baseline or final MMP-3 levels, DAS28-CRP, and rate of pre-existing lesions at baseline were all significantly higher than those of the non-progressive group (p=0.017, p=0.043, p=0.002, p=0.008, p<0.001, and p=0.008 respectively). A multivariate logistic regression analysis demonstrated that DAS28-CRP at baseline was a risk factor for radiographic progression (p=0.018, odds ratio: 2.54, 95% confidence interval: 1.17-5.51). Our findings indicate that higher disease activity might influence the progression of UCLs in patients with RA.

A new method to evaluate hip joint damage in ankylosing spondylitis / 中华风湿病学杂志

Objective In order to assess the structure damage of hip joint in ankylosing spondylitis (AS), a new radiograph-based scoring method was developed according to the radiological characteristics of hip involvement in AS, as well referring to prior existing scoring indexes. Methods A new scoring method consti-tuted of erosion, sclerosis and joint space narrowing was developed, pelvis anterior-posterior plain films acquired from patients with AS at baseline and follow-up were collected and assessed by two physicians who were trained in image reading by radiologists. All films were scored independently and blindly. Intra- and inter-reader reliability were assessed by intra-class correlation coefficient (ICC), the feasibility of this new scoring method was assessed by the mean time acquired to score a plain (two hips), its ability to detect the change of structure damage was assessed by the comparison of score differences between baseline and different follow-ups. The date were analyzed by paired-t test or nonparametric tests. Analysis of Variance (ANOVA) or nonparametric tests were utilized for the comparison of means of quantitative variables among the three groups, while Chi-square test for rates of categorical variables. Results No statistically significant differences existed in demographic data and suspected risk factors among the three groups at baseline (P>0.05). Intra-observer reliability was good (0.84 and 0.89), as well as the inter-observer reliability (0.72), the mean time needed to score was (33 ±10) seconds. Score changes were not statistically significant in the groups with follow-up duration of 1-2 and 3-4 years, but in the group of over 5 years, baseline/final scores assessed by the two observers were (6.0±2.7/7.5±3.7) and (5.6±2.1/7.1±3.6), respectively, both changes were statistically significant (t=2.86, Z=-2.99; P<0.01). Conclusion This new method is not only reproducible and easy to operate in clinic practice, but also can tell the changes of hip joint structure damage in the interval of over 5 years, further validation is requeired to demonstrate its discriminability in large populations.

Effect of Tripterygium Glycosides Tablets in treating rheumatoid arthritis:a systematic review and Meta-analysis / 中国中药杂志

To evaluate the effect of Tripterygium Glycosides Tablets extract in the treatment of rheumatoid arthritis( RA). Clinical trials of treating rheumatoid arthritis with Tripterygium Glycosides Tablets published by Meta-analysis were retrieved from EMbase,PubMed,Clinical Trials,Web of Science,Cochrane Library,CNKI,Wanfang,VIP,CBM and Chi CTR,and comprehensively analyzed. A total of 3 studies were enrolled,the modified Sharp score( m TSS),tender join joint erosions( JE) and joint space narrowing( JSN) of Tripterygium Glycosides Tablets group were significant superior to those of control group,including positive drugs methotrexate( MTX) and salazopyridine( SSZ)( P<0. 01). Tripterygium Glycosides Tablets had an effect in treating RA. Due to the small sample size,this study shall be verified with high-quality,large-sample-size double-blinded RCTs.

IL-6, PF-4, sCD40 L, and homocysteine are associated with the radiological progression of cerebral small-vessel disease: a 2-year follow-up study.

BACKGROUND: Endothelial dysfunction (ED) is involved in the pathogenesis of cerebral small vessel disease (SVD), however, it is not clear if specific biomarkers related to ED are associated with radiological progression of SVD. METHODS: A single-center, prospective cohort study was conducted among consecutive, adult patients with SVD. Logistic regression was used to analyze the association of each baseline biomarker (highest vs lowest tertile) and the MRI radiological outcome after 2 years. The mean Z-score for vascular inflammation (VI) combined soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble platelet selectin (sP-selectin), CD40 ligand (sCD40 L), platelet factor-4 (PF-4) and homocysteine; Z-score for systemic inflammation (SI) combined high-sensitivity C-reactive protein (hsCRP), interleukin-1α and -6 (IL-1α and IL-6, respectively) and tumor necrosis factor-α (TNF-α). RESULTS: The study group comprised 123 patients (age, mean±SD: 72.2±8 years, 49% females), with lacunar stroke (n=49), vascular dementia (n=48), and vascular parkinsonism (n=26). Moreover, 34.9% patients experienced radiological progression, 43% had progression of isolated white matter lesions (WMLs), 23.2% had new lacunes, and 34.8% had both WMLs progression and new lacunes. After adjustment for confounders (age, sex, blood pressure, MRI lesions load), the PF-4 (OR; 95% CI 5.5; 1.5-21), sCD40L (4.6; 1.1-18.6), IL-6 (7.4; 1.48-37), Z-score for VI (4.5; 1.1-18.6), and, marginally, homocysteine (4.1; 0.99-17) were associated with the risk of any radiological progression; further, homocysteine (2.4; 1.4-14), Z-score for SI (2.1; 1.2-14) and, marginally, IL-6 (6.0; 0.95 -38) were related to the development of new lacunes; PF-4 (7.9; 1.6-38) and, marginally, the Z-score for VI (4.2; 0.9-19.5) were correlated with the risk of WMLs progression. Additional adjustment for clinical SVD manifestations did not significantly alter the results. CONCLUSION: The data supports the concept that ED modulates the radiological progression of SVD and WMLs and lacunes are associated with different inflammatory markers.

Gender Differences in Axial Spondyloarthritis: Women Are Not So Lucky.

PURPOSE OF REVIEW: Ankylosing spondylitis (AS) was historically seen as a predominantly male disease. However, more recent data showed a more homogenous sex prevalence. Unfortunately, in many studies in axial spondyloarthritis (axSpA), the number of women included is low and the analyses are often not stratified for gender distribution. The purpose of this review is to aggregate the existing data on gender differences in axSpA in order to increase the awareness that female axSpA patients are still under-recognized. RECENT FINDINGS: Several studies considering gender differences revealed that female axSpA patients had different disease manifestations due to different immunological, hormonal, and genetic responses. For instance, allelic frequencies of the AHNK-gene and tissue non-specific alkaline phosphatase (TNAP) haplotypes differed between men and women with ankylosing spondylitis (AS). In addition, different levels of tumor necrosis factor (TNF), interleukins IL-6, IL-17, and IL-18, were found between the two sexes. Furthermore, female patients show a higher diagnostic delay compared to males. Several studies indicate a higher frequency of extra-articular manifestations (EAM) in female axSpA patients, such as enthesitis, psoriasis, and inflammatory bowel disease (IBD), whereas acute anterior uveitis is more prevalent in male patients. Male AS patients more frequently show a higher Bath Ankylosing Spondylitis Radiology Index (BASRI) scores and modified Stoke Ankylosing Spondylitis Spine Scores (mSASSS) than females, which indicates that males have higher radiological damage and radiographic progression. However, disease activity (BASDAI) and quality of life (AsQol) scores are significantly higher in women, and more importantly, they have significantly lower response rates to treatment with TNF inhibitors (TNFi) and a significantly lower drug adherence. Despite the fact that men with axial SpA have a worse radiologic prognosis, women have a high disease burden, in part because they have a longer delay in diagnosis, higher disease activity, and significantly less responsiveness to treatment with TNFi.

Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study.

BACKGROUND: Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined. METHODS: Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently. RESULTS: Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups. CONCLUSIONS: During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA. TRIAL REGISTRATION: This is a follow-up study. Original trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

Statin use and knee osteoarthritis progression: Results from a post-hoc analysis of the SEKOIA trial.

OBJECTIVE: Epidemiological and experimental studies have suggested that lipid disorders might be involved in the pathophysiology of knee osteoarthritis (OA). Studies assessing the effect of statins on knee OA progression have shown conflicting results. We investigated the impact of statin use on radiological progression in patients with radiological and symptomatic knee OA. METHODS: In total, 336 patients from the placebo arm of SEKOIA trial completed the 3-year follow-up and were included in this post-hoc analysis. Statin use was recorded at baseline interview. Minimal medial tibiofemoral joint space was measured on plain radiographs by an automated method at baseline and then annually. Radiologic progression was defined as joint space narrowing≥0.5mm over 3 years. RESULTS: Overall, 71 patients were statin users (21.1%). They had a higher BMI (31.1±5.3 vs. 29.3±5.2kg/m2, P=0.008), a higher sum of metabolic factors (≥3 factors: 43.7% vs 7.2%; P for trend<0.001) and a higher rate of radiological progression (49.3% vs. 32.1%, P=0.007) as compared to statin non-users. The significant association between radiological progression and statin use was independent of age, gender, WOMAC global score, disease duration, baseline joint space width, hypertension, type 2 diabetes, obesity (BMI>30kg/m2) and cardiovascular diseases [relative risk 1.49 (95% CI: 1.10-2.02), P=0.010]. CONCLUSION: Among patients with knee OA, statin use was associated with radiological worsening over 3 years, regardless of other potential confounding factors (obesity, type 2 diabetes, hypertension, disease duration, symptom intensity and radiological severity).

Association between hemostatic markers, serum lipid fractions and progression of cerebral small vessel disease: A 2-year follow-up study.

INTRODUCTION: Little is known if hemostatic markers and serum lipid fractions can predict further radiological progression beyond vascular risk factors in cerebral small vessel disease (SVD). We investigated whether they are associated with SVD radiological progression and if they are related to different SVD clinical manifestations. METHODS: A single-center, prospective, cohort study with 2 years of radiological follow-up was performed in consecutive patients with different SVD manifestations. The study group consisted of 123 patients: 49 with lacunar stroke (LS), 48 with vascular dementia (VaD) and 26 with vascular parkinsonism (VaP). We assessed SVD progression by a visual SVD scale. We determined the relationship between serum or plasma concentrations of tissue factor (TF), thrombomodulin, beta-thromboglobulin (BTG), fibrinogen, D-dimer and total cholesterol, HDL-C, LDL-C, triglycerides and SVD progression by logistic regression analysis. RESULTS: 34.9% patients had SVD radiological progression: 43% had isolated WMLs progression, 23.2% had new lacunes, 34.8% had both WMLs progression and new lacunes. Fibrinogen [OR 1.02 (95% CI 1.006-1.011] was significantly associated with risk of new lacunes or WMLs progression regardless of the clinical SVD manifestation. While low HDL [OR 0.96 (0.93-1)] and TF [OR 1.07 (0.99-1.1)] were marginally associated with new lacunes, BTG [OR 1.005 (0.99-1.01)] was associated with WMLs progression. CONCLUSION: We found a relationship between fibrinogen and risk of radiological progression of SVD regardless of the clinical SVD manifestation. In addition, lower HDL and increased TF predicted development of new lacunes, and higher BTG was associated with risk of WMLs progression.