Predictors of mortality for dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 and optimal treatment.

OBJECTIVES: To explore the risk factors of early death in dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM). To explore the optimal treatment regimen for patients with anti-MDA5-DM. METHODS: Patients with newly onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for 6 months. Patients were divided into five groups based on initial treatments. The major outcome was mortality in 6 months. Secondary outcomes included remission and severe infection. RESULTS: A total of 214 patients were included in the study. During 6 month follow-up, 63 patients (30.14%) died, 112 patients (53.59%) achieved remission, 52 patients (24.88%) experienced serious infection and 5 patients (2.34%) were lost. Independent risk factors of mortality in the first 6 months after diagnosis were as follows: age> 53 years, skin ulcer, peripheral blood lymphocyte count (LYMP)≤ 0.6×109/L, lactate dehydrogenase (LDH) > 500 U/L, C reactive protein (CRP) > 5mg/L, anti-Ro52 antibody and ground-glass opacity (GGO) score> 2. On the contrary, prophylactic use of the compound sulfamethoxazole (SMZ Co) was independent protective factor. The five-category treatment was not an independent influencing factor of early death, but subgroup analysis found that patients with rapidly progressive interstitial lung disease (RPILD) responded better to a triple combination of high-dose glucocorticoids (GC), calcineurin inhibitors (CNI) and cyclophosphamide (CYC) or a triple combibation of GC, CNI and tofacitinib (TOF). CONCLUSIONS: Advanced age, skin ulcer, lymphopenia, anti-Ro52 antibody and higher levels of LDH, CRP and GGO score increase the risk of early death for MDA5-DM, while prophylactic use of SMZ Co is protective. Aggressive therapy with combined immunosuppressants may improve the short-term prognosis of anti-MDA5-DM with RPILD.

Alterations in the human oral microbiota in systemic lupus erythematosus.

BACKGROUND: Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota. METHODS: We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized. RESULTS: The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848-0.9483, p < 0.0001), 0.8422 (95% CI 0.7687-0.9157, p < 0.0001), and 0.8406 (95% CI 0.7677-0.9135, p < 0.0001) in the derivation, validation, and cross-regional validation groups, respectively. Moreover, as disease activity increased, Abiotrophia and Lactobacillales increased, while Phyllobacterium and unclassified Micrococcusaceae decreased. Finally, nine OTUs were selected to construct a classifier distinguishing posttreatment SLE patients from healthy controls, which achieved a diagnostic efficacy of 0.9942 (95% CI 0.9884-1, p < 0.0001). CONCLUSIONS: Our study comprehensively characterizes the oral microbiome of SLE and shows the potential of the oral microbiota as a non-invasive diagnostic biomarker in SLE.

Compounded sulfamethoxazole improved the prognosis of dermatomyositis patients positive with anti-melanoma differentiation-associated gene 5.

OBJECTIVES: Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). METHODS: Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups-coSMZ and non-coSMZ-based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. RESULTS: Compared with the non-coSMZ group (n = 93), the coSMZ group (n = 121) had lower mortality (18.8% vs 51.1%; P < 0.001) and a lower incidence of PJP (6.8% vs 15.2%; P = 0.040) and fatal infection (16.1% vs 3.3%; P = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102-0.878), P = 0.028]. CONCLUSION: Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP.

Teriparatide prevented synovial inflammation and cartilage destruction in mice with DMM.

AIM: Emerging data have demonstrated that low-grade inflammation in osteoarthritis, a long-held degenerative disease. The inflamed synovium produces various cytokines that induce cartilage destruction and joint pain. A previous study showed that teriparatide, an FDA approved anti-osteoporotic drug, may enhance cartilage repair. Our study focuses on its role in OA synovitis. MATERIALS AND METHODS: Primary mouse articular chondrocytes were used to determine the most potent cytokines involved in OA inflammation and cartilage destruction. A destabilization of the medial meniscus mouse model was established to investigate the effect of teriparatide in OA, particularly, on synovial inflammation and cartilage degradation. RESULTS: In vitro experiments showed that TNF-α was the most potent inducer of cartilage matrix-degrading enzymes, and that teriparatide antagonized the TNF-α of effect. Consistently, articular cartilage samples from TNF-α transgenic mice contained more MMP-13 positive chondrocytes than those from wild type mice. In addition, more type II collagen was cleaved in human OA cartilage than in normal cartilage samples. CONCLUSIONS: Teriparatide can prevent synovitis and cartilage degradation by suppressing TNF-α mediated MMP-13 overexpression. Together with its chondroregenerative capability, teriparatide may be the first effective disease modifying osteoarthritis drug.

Clinical features and independent predictors of Behçet's disease associated with myelodysplastic syndrome.

OBJECTIVES: To investigate the correlation of Behçet's disease (BD) with myelodysplastic syndrome (MDS) and identify the predictive risk factors in Chinese patients. METHODS: A retrospective study of BD associated with MDS (BD-MDS) patients from the First Affiliated Hospital of Zhengzhou University was conducted. RESULTS: Among 15 BD-MDS patients, 10 were females and 5 males. While 13 (86.7%) patients had abnormal karyotype, 11 patients with trisomy 8. 10 (66.7%) had gastrointestinal (GI) involvement. Compared with 60 general BD patients without MDS, the BD-MDS patients were significantly older. In addition, fever and GI involvement were more common in BD-MDS patients, whereas these patients had lower levels of leukocyte count, haemoglobin, and platelet count (p<0.05). Logistic regression analysis showed that GI involvement, low haemoglobin, and high ESR level were independently associated with the development of MDS in BD patients. BD-MDS patients with GI involvement (IBD-MDS) were usually much older and have more fever than IBD patients without MDS, as well as lower leukocyte count, haemoglobin level, platelet count, and higher erythrocyte sedimentation rate (ESR) and C-reactive protein levels (p<0.05). By comparison with 60 primary MDS patients without BD, the BD-MDS patients had more abnormal karyotypes and more trisomy 8 (p<0.05), while the distribution of 2016 WHO subtypes of MDS and IPSS-R categories were similar. CONCLUSIONS: Our findings suggest that cytogenetic abnormalities, especially trisomy 8, may play a role in the association of GI involvement, BD, and MDS. GI involvement, low haemoglobin, and high ESR level were independent predictors for MDS development in BD patients.

An Autophagy-Associated Prognostic Gene Signature for Breast Cancer.

Autophagy is closely related to breast cancer and has the dual role of promoting and inhibiting the progression of breast cancer. In this study, we aimed to establish an autophagy-related gene signature for the prognosis of breast cancer. A gene signature composed of the eight most survival-relevant autophagy-associated genes was identified by least absolute shrinkage and selection operator (LASSO) regression analysis. A risk score was calculated based on the gene signature, which divided breast cancer patients into low- or high-risk groups and showed good and poor prognosis, respectively. The risk score displayed good prognostic performance in both the training cohort (TCGA, 1-10-year AUC > 0.63) and the validation cohort (GEO, 1-10-year AUC > 0.66). The multivariate Cox regression and stratified analysis revealed that the risk score was an independent prognostic factor for breast cancer patients. Moreover, the high-risk score was associated with higher infiltration of neutrophils and M2-polarized macrophages, and lower infiltration of resting memory CD4+ T cells, CD8+ T cells, and NK cells. Finally, the high-risk score was associated with myc target, glycolysis, and mTORC1 signaling. The risk score developed based on the autophagy-associated gene signature was an independent prognostic biomarker for breast cancer.

Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis.

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) in DM patients positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibody (MDA5-DM) often have a poor prognosis, frequently fatal. As there is a scarcity of data regarding the effect of intravenous immunoglobulin (IVIG) on RP-ILD in MDA5-DM patients (MDA5-RPILD), we conducted this study to determine the efficacy of a IVIG add-on initial treatment. METHODS: Patients with newly-onset MDA5-RPILD from September 2018 to June 2020 were retrospectively reviewed for 6 months in the First Affiliated Hospital of Zhengzhou University. They were divided into two groups: IVIG and non-IVIG groups. The major measurement of treatment outcome was the difference in the mortality in 3-month and 6-month between two group patients. Other relevant indicators were also recorded, including the incidence of infection, the dosages of GCs, the remission rate and the variables in laboratory data. RESULTS: The IVIG group (n = 31) showed significantly lower 6-month mortality rate than the non-IVIG group (n = 17) (22.6% vs 52.9%; P =0.033). The IVIG group patients had a higher remission rate at 3 months (71.0% vs 41.2%; P =0.044). Gradual reduction was observed in the first 3 months with regard to the titre of anti-MDA5 autoantibody, the serum level of ferritin and the ground glass opacification GGO scores. CONCLUSION: IVIG adjunct therapy is a very effective first-line treatment for patients with MDA5-RPILD. IVIG may increase the survival and remission rate by lowering ferritin concentration, anti-MDA5 titre and GGO score.

Anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis exhibit three clinical phenotypes with different prognoses.

OBJECTIVES: We aimed to identify different subtypes of dermatomyositis (DM) patients positive with anti-melanoma differentiation-associated gene 5 antibody (DM-MDA5+) for customised treatments to improve the outcomes. METHODS: Among 96 DM-MDA5+ patients, subgroups with similar phenotypes were delineated using hierarchical clustering analysis of the clinico-biological characteristics. Classification and regression trees were used to build a classification model and survival analysis was used to evaluate the prognoses of subgroups. RESULTS: Three subgroups were identified among 96 DM-MDA5+ patients, and patients in different subgroups had highly heterogenic manifestations and outcomes. Cluster 1 patients were referred to as mild group of rheumatologic patterns with good prognosis. Cluster 2 patients were referred to as young typical DM group with good prognosis. Cluster 3 patients were referred to as elderly rapidly progressive interstitial lung disease (RPILD) group with poor prognosis. A predictive model to classify patients was established, and three critical factors were found, including age, serum ferritin and myalgia. CONCLUSIONS: DM-MDA5+ patients have a poor short-term prognosis. Three clinical phenotypes with different prognoses were identified in DM-MDA5+ patients.

Clinical characteristics, outcome and prognostic factors in critically ill patients with lupus nephritis.

OBJECTIVES: To describe the clinical characteristics and outcome of patients with lupus nephritis (LN) in intensive care unit (ICU), identify prognostic factors and construct a predictive model of in-ICU survival. METHODS: A total of 505 ICU admissions of lupus patients were screened and LN patients confirmed by renal biopsy were enrolled. Clinical characteristics and outcome of patients in ICU were collected. A logistic regression analysis was performed to identify independent prognostic factors and a nomogram was plotted to construct a predictive model. RESULTS: A total of 70 patients with LN were enrolled. The median age of the patients was 28.5 years, and the median course of LN was two months. Renal pathology classes indicated that 38 patients were class IV, 11 were class IV+V, and 10 were class III. The most common primary cause of ICU admission was infection in 40 patients, followed by LN in 11 patients. Forty-one patients died in ICU. The multivariate analyses revealed that lactic acid (OR 1.682 [2.130-17.944], p=0.001), gamma-glutamyl transpeptidase (OR 1.057 [1.009-1.107], p=0.020), APACHE II (OR 3.852 [1.176-12.618], p=0.026), vasopressor (OR 10.571 [1.615-69.199], p=0.014) and platelet count (OR 0.967 [0.941-0.993], p=0.013) were independently associated with ICU survival of critical LN patients. A predictive model was constructed and validated. CONCLUSIONS: This study is the first to elucidate the features and identify prognostic factors in critically ill patients with LN. These findings could help clinicians to early identify high-risk patients of mortality, which consequently may reduce the mortality of critically ill patients with LN.

Association between triglyceride-glucose index and nonalcoholic fatty liver disease in type 2 diabetes mellitus.

BACKGROUND: Lipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population. METHODS: A total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD. RESULTS: Logistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03-5.27; P < 0.001) for NAFLD in the highest TyG quartile after adjustment for known confounders. In stratified analysis, an elevated TyG index were more remarkably associated with NAFLD in younger patients (< 65 years; OR, 2.35; 95% CI, 1.83-3.02; P < 0.001), females (OR, 2.69; 95% CI, 1.67-4.32; P < 0.001), patients with BMI < 25 kg/m2 (OR, 2.80; 95% CI, 2.01-3.91; P < 0.0001), and with lower high-density lipoprotein cholesterol (< 1 mmol/L; OR, 2.76; 95% CI, 1.98-3.83; P < 0.001). CONCLUSION: The TyG index is significantly associated with NAFLD and shows superior ability for identify NAFLD risk compared with other lipid and glycemic parameters in T2DM.

Evaluation of a proprietary software application for motion monitoring during stereotactic paraspinal treatment.

PURPOSE: Stereotactic paraspinal treatment has become increasingly popular due to its favorable clinical outcome. An often-overlooked factor that compromises the effectiveness of such treatment is the patients' involuntary intrafractional motion. This work introduces and validates a proprietary software application that quantifies such motion for accurate patient monitoring during treatment. METHODS: The software uses a separate full-trajectory cone-beam computed tomography (CBCT) after daily patient setup to establish reference projections. Once treatment starts, the software grabs the intrafraction motion review (IMR) image acquired by TrueBeam via the Varian iTools Capture software and compares it against the corresponding reference projection to instantly determine the 2D shifts of the vertebrae being monitored using the classical downhill simplex optimization method. To evaluate its performance, an anthropomorphic phantom was shifted 0, 0.6, 1.2, 1.8, 2.4, 3.0, and 5 mm in three orthogonal directions, immediately after the full-trajectory CBCT but prior to treatment. Depending on the scenario of shift, a nine-field fixed gantry intensity-modulated radiation therapy (IMRT) plan and/or a four partial-posterior-arcs volume-modulated radiation therapy (VMAT) plan were delivered. For the IMRT plan, three IMR images were acquired sequentially every 200 monitor units (MU) at each treatment angle. For the VMAT plan, one IMR image was acquired every 15° of each arc. For each IMR image, the software-reported 2D shift was compared with the ground truth. Certain tests were repeated with 1°, 2°, and 3° of rotation, pitch, and roll, respectively. Some of these tests were also repeated independently on separate days. RESULTS: Based on the group of tests that involved only the IMRT delivery, the maximum standard deviation of the software-reported shifts for each set of three IMR images was 0.16 mm, with 95th percentile at 0.02 mm. For translational shift, the maximum registration error was 0.44 mm, with 95th percentile at 0.23 mm. Left unaccounted for, rotation and pitch degraded the registration accuracy mainly in the longitudinal direction, while roll degraded it mainly in the lateral direction. The degradation of registration accuracy is positively related to the degree of rotation, pitch, and roll. The maximum registration errors under 3° rotation, pitch, and roll were 2.97, 1.44, 2.72 mm, respectively. Based on the group of tests that compared IMRT delivery with VMAT delivery, the registration errors slightly increased as magnitude of shifts increased; however, they were well under the 0.5-mm threshold. No significant differences in registration errors were observed between IMRT and VMAT deliveries. In addition, the variation in registration errors among different days was limited for both IMRT and VMAT deliveries. CONCLUSIONS: Our proprietary software has high repeatability, both intrafractionally and interfractionally, and high accuracy in registering IMR images with the reference projections for motion monitoring, regardless of the magnitude of shifts or treatment delivery technique. Rotation, pitch, and roll degrade registration accuracy and need to be accounted for in the future work.

Intrafractional accuracy and efficiency of a surface imaging system for deep inspiration breath hold during ablative gastrointestinal cancer treatment.

PURPOSE: Beam gating with deep inspiration breath hold (DIBH) usually depends on some external surrogate to infer internal target movement, and the exact internal movement is unknown. In this study, we tracked internal targets and characterized residual motion during DIBH treatment, guided by a surface imaging system, for gastrointestinal cancer. We also report statistics on treatment time. METHODS AND MATERIALS: We included 14 gastrointestinal cancer patients treated with surface imaging-guided DIBH volumetrically modulated arc therapy, each with at least one radiopaque marker implanted near or within the target. They were treated in 25, 15, or 10 fractions. Thirteen patients received treatment for pancreatic cancer, and one underwent separate treatments for two liver metastases. The surface imaging system monitored a three-dimensional surface with ± 3 mm translation and ± 3° rotation threshold. During delivery, a kilovolt image was automatically taken every 20° or 40° gantry rotation, and the internal marker was identified from the image. The displacement and residual motion of the markers were calculated. To analyze the treatment efficiency, the treatment time of each fraction was obtained from the imaging and treatment timestamps in the record and verify system. RESULTS: Although the external surface was monitored and limited to ± 3 mm and ± 3°, significant residual internal target movement was observed in some patients. The range of residual motion was 3-21 mm. The average displacement for this cohort was 0-3 mm. In 19% of the analyzed images, the magnitude of the instantaneous displacement was > 5 mm. The mean treatment time was 17 min with a standard deviation of 4 min. CONCLUSIONS: Precaution is needed when applying surface image guidance for gastrointestinal cancer treatment. Using it as a solo DIBH technique is discouraged when the correlation between internal anatomy and patient surface is limited. Real-time radiographic verification is critical for safe treatments.

Comparative study of SRS end-to-end QA processes of a diode array device and an anthropomorphic phantom loaded with GafChromic XD film.

PURPOSE: End-to-end testing (E2E) is a necessary process for assessing the readiness of the stereotactic radiosurgery (SRS) program and annual QA of an SRS system according to the AAPM MPPG 9a. This study investigates the differences between using a new SRS MapCHECK (SRSMC) system and an anthropomorphic phantom film-based system in a large network with different SRS delivery techniques. METHODS AND MATERIALS: Three SRS capable Linacs (Varian Medical Systems, Palo Alto, CA) at three different regional sites were chosen to represent a hospital network, a Trilogy with an M120 multi-leaf collimator (MLC), a TrueBeam with an M120 MLC, and a TrueBeam Stx with an HD120 MLC. An anthropomorphic STEEV phantom (CIRS, Norfolk, VA) and a phantom/diode array: StereoPHAN/SRSMC (Sun Nuclear, Melbourne, FL) were CT scanned at each site. The new STV-PHANTOM EBT-XD films (Ashland, Bridgewater, NJ) were used. Six plans with various complexities were measured with both films and SRSMC in the StereoPHAN to establish their dosimetric correlations. Three SRS cranial plans with a total of sixteen fields using dynamic conformal arc and volumetric-modulated arc therapy, with 1-4 targets, were planned with Eclipse v15.5 treatment planning system (TPS) using a custom SRS beam model for each machine. The dosimetric and localization accuracy were compared. The time of analysis for the two systems by three teams of physicists was also compared to assess the throughput efficiency. RESULTS: The correlations between films and SRSMC were found to be 0.84 (p = 0.03) and 0.16 (p = 0.76) for γ (3%, 1 mm) and γ (3%, 2 mm), respectively. With film, the local dose differences (ΔD) relative to the average dose within the 50% isodose line from the three sites were found to be -3.2%-3.7%. The maximum localization errors (Elocal ) were found to be within 0.5 ± 0.2 mm. With SRSMC, the ΔD was found to be within 5% of the TPS calculation. Elocal were found to be within 0.7 to 1.1 ± 0.4 mm for TrueBeam and Trilogy, respectively. Comparing with film, an additional uncertainty of 0.7 mm was found with SRSMC. The delivery and analysis times were found to be 6 and 2 h for film and SRSMC, respectively. CONCLUSIONS: The SRS MapCHECK agrees dosimetrically with the films within measurement uncertainties. However, film dosimetry shows superior sub-millimeter localization resolving power for the MPPG 9a implementation.

ATF4-modified serum exosomes derived from osteoarthritic mice inhibit osteoarthritis by inducing autophagy.

Activating transcription factor 4 (ATF4) is critical for chondrocyte proliferation and bone formation. Exosomes are considered as promising gene-delivery vehicles for the treatment of osteoarthritis (OA). This study utilized the serum-derived exosomes from OA mice as the gene-delivery vehicles for ATF4 gene therapy and explored their therapeutic effects on OA. Meniscus injury-induced OA model was established by the excision of anterior part of medial meniscus in the right knee of C57BL/6J mice. Exosomes were isolated from serum samples of sham and OA mice, and were referred to as sham-Exo and OA-Exo, respectively. ATF4-overexpressing OA-Exo (ATF4-OA-Exo) was developed by introducing ATF4 mRNA into OA-Exo via electroporation. Four weeks after surgery, OA mice received intra-articular injections of sham-Exo, OA-Exo, and ATF4-OA-Exo, respectively. The results showed that intra-articular injection of ATF4-OA-Exo alleviated articular cartilage degeneration or damage and inflammatory response of OA mice. Autophagy was weakened in knee joint cartilage of OA mice, which was partially restored by intra-articular injection of ATF4-OA-Exo. Further in vitro assays revealed that ATF4-OA-Exo promoted chondrocyte autophagy and inhibited chondrocyte apoptosis in the TNF-α- or tunicamycin-treated chondrocytes. Together, ATF4-modified serum exosomes derived from OA mice protect cartilage and alleviate OA progression by inducing autophagy.

Accuracy and efficiency of respiratory gating comparable to deep inspiration breath hold for pancreatic cancer treatment.

PURPOSE: Deep inspiration breath hold (DIBH) and respiratory gating (RG) are widely used to reduce movement of target and healthy organs caused by breathing during irradiation. We hypothesized that accuracy and efficiency comparable to DIBH can be achieved with RG for pancreas treatment. METHODS AND MATERIALS: Twenty consecutive patients with pancreatic cancer treated with DIBH (eight) or RG (twelve) volumetric modulated arc therapy during 2017-2019 were included in this study, with radiopaque markers implanted near or in the targets. Seventeen patients received 25 fractions, while the other three received 15 fractions. Only patients who could not tolerate DIBH received RG treatment. While both techniques relied on respiratory signals from external markers, internal target motions were monitored with kV X-ray imaging during treatment. A 3-mm external gating window was used for DIBH treatment; RG treatment was centered on end-expiration with a duty cycle of 40%, corresponding to an external gating window of 2-3 mm. During dose delivery, kV images were automatically taken every 20◦ or 40◦ gantry rotation, from which internal markers were identified. The marker displacement from their initial positions and the residual motion amplitudes were calculated. For the analysis of treatment efficiency, the treatment time of every session was calculated from the motion management waveform files recorded at the treatment console. RESULTS: Within one fraction, the displacement was 0-5 mm for DIBH and 0-6 mm for RG. The average magnitude of displacement for each patient during the entire course of treatment ranged 0-3 mm for both techniques. No statistically significant difference in displacement or residual motion was observed between the two techniques. The average treatment time was 15 min for DIBH and 17 min for RG, with no statistical significance. CONCLUSIONS: The accuracy and efficiency were comparable between RG and DIBH treatment for pancreas irradiation. RG is a feasible alternative strategy to DIBH.

Commissioning of optical surface imaging systems for cranial frameless stereotactic radiosurgery.

PURPOSE: This study aimed to evaluate and compare different system calibration methods from a large cohort of systems to establish a commissioning procedure for surface-guided frameless cranial stereotactic radiosurgery (SRS) with intrafractional motion monitoring and gating. Using optical surface imaging (OSI) to guide non-coplanar SRS treatments, the determination of OSI couch-angle dependency, baseline drift, and gated-delivered-dose equivalency are essential. METHODS: Eleven trained physicists evaluated 17 OSI systems at nine clinical centers within our institution. Three calibration methods were examined, including 1-level (2D), 2-level plate (3D) calibration for both surface image reconstruction and isocenter determination, and cube phantom calibration to assess OSI-megavoltage (MV) isocenter concordance. After each calibration, a couch-angle dependency error was measured as the maximum registration error within the couch rotation range. A head phantom was immobilized on the treatment couch and the isocenter was set in the middle of the brain, marked with the room lasers. An on-site reference image was acquired at couch zero, the facial region of interest (ROI) was defined, and static verification images were captured every 10° for 0°-90° and 360°-270°. The baseline drift was assessed with real-time monitoring of the motionless phantom over 20 min. The gated-delivered-dose equivalency was assessed using the electron portal imaging device and gamma test (1%/1mm) in reference to non-gated delivery. RESULTS: The maximum couch-angle dependency error occurs in longitudinal and lateral directions and is reduced significantly (P < 0.05) from 1-level (1.3 ± 0.4 mm) to 2-level (0.8 ± 0.3 mm) calibration. The MV cube calibration does not further reduce the couch-angle dependency error (0.8 ± 0.2 mm) on average. The baseline drift error plateaus at 0.3 ± 0.1 mm after 10 min. The gated-delivered-dose equivalency has a >98% gamma-test passing rate. CONCLUSION: A commissioning method is recommended using the 3D plate calibration, which is verified by radiation isocenter and validated with couch-angle dependency, baseline drift, and gated-delivered-dose equivalency tests. This method characterizes OSI uncertainties, ensuring motion-monitoring accuracy for SRS treatments.

Laboratory-confirmed bloodstream infection in systemic lupus erythematosus: Risk profiling and short-term mortality.

OBJECTIVES: To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients.Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013-2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. RESULTS: Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. CONCLUSION: Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.

Predictive factors and prognosis of macrophage activation syndrome associated with adult-onset Still's disease.

OBJECTIVES: To summarise the clinical data of adult-onset Still's disease (AOSD) patients and analyse their clinical manifestations, predictors for the formation and prognosis of macrophage activation syndrome (MAS). METHODS: A retrospective analysis was performed on the clinical data of 182 AOSD hospitalised patients from the Department of Rheumatology of the First Affiliated Hospital of Zhengzhou University, China from January 2012 to August 2018, including 11 patients with pathogenesis of MAS. RESULTS: Compared with the patients without MAS, the patients with MAS had a higher incidence of splenomegaly and pericarditis at the initial diagnosis of AOSD. The number of platelets (PLT) and the concentration of fibrinogen (FIB), D-Dimer and ferritin were significantly higher in AOSD-MAS patients. Multivariate regression analysis showed that splenomegaly (OR: 5.748, 95% CI: 1.378-23.984, p=0.016), pericarditis (OR: 6.492, 95% CI: 1.43-29.461, p=0.015), and ferritin >2000 µg/L (OR: 4.715, 95% CI: 1.12-19.86, p=0.035) were risk factors for MAS. Survival analysis indicated that the mortality of AOSD-MAS patients was significantly higher than patients without MAS. CONCLUSIONS: Splenomegaly, pericarditis and elevated ferritin concentration are risk factors for MAS formation in AOSD patients. MAS resulted in a significant decrease in the survival rate of the AOSD patients.

Intrafraction tumor motion during deep inspiration breath hold pancreatic cancer treatment.

PURPOSE: Beam gating with deep inspiration breath hold (DIBH) has been widely used for motion management in radiotherapy. Normally it relies on some external surrogate for estimating the internal target motion, while the exact internal motion is unknown. In this study, we used the intrafraction motion review (IMR) application to directly track an internal target and characterized the residual motion during DIBH treatment for pancreatic cancer patients through their full treatment courses. METHODS AND MATERIALS: Eight patients with pancreatic cancer treated with DIBH volumetric modulated arc therapy in 2017 and 2018 were selected for this study, each with some radiopaque markers (fiducial or surgical clips) implanted near or inside the target. The Varian Real-time Position Management (RPM) system was used to monitor the breath hold, represented by the anterior-posterior displacement of an external surrogate, namely reflective markers mounted on a plastic block placed on the patient's abdomen. Before each treatment, a cone beam computed tomography (CBCT) scan under DIBH was acquired for patient setup. For scan and treatment, the breath hold reported by RPM had to lie within a 3 mm window. IMR kV images were taken every 20° or 40° gantry rotation during dose delivery, resulting in over 5000 images for the cohort. The internal markers were manually identified in the IMR images. The residual motion amplitudes of the markers as well as the displacement from their initial positions located in the setup CBCT images were analyzed. RESULTS: Even though the external markers indicated that the respiratory motion was within 3 mm in DIBH treatment, significant residual internal target motion was observed for some patients. The range of average motion was from 3.4 to 7.9 mm, with standard deviation ranging from 1.2 to 3.5 mm. For all patients, the target residual motions seemed to be random with mean positions around their initial setup positions. Therefore, the absolute target displacement relative to the initial position was small during DIBH treatment, with the mean and the standard deviation 0.6 and 2.9 mm, respectively. CONCLUSIONS: Internal target motion may differ from external surrogate motion in DIBH treatment. Radiographic verification of target position at the beginning and during each fraction is necessary for precise RT delivery. IMR can serve as a useful tool to directly monitor the internal target motion.

Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. METHODS: We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. RESULTS: Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). CONCLUSION: Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.