Circulating cell-free DNA methylation-based multi-omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.

Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer.

BACKGROUND: The role of CD161 expression on CD8+ T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161+CD8+ T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161+CD8+ T cell infiltration in PDAC. METHODS: This study included 186 patients with confirmed PDAC histology after radical resection. CD161+CD8+ T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status. RESULTS: We observed significant associations between tumor-infiltrating CD161+CD8+ T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161+CD8+ T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161+CD8+ T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161+CD8+ T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161+CD8+ T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161+CD8+ T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161+CD8+ T cells as a unique subtype of responsive CD8+ T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules. CONCLUSION: CD161+CD8+ T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161+CD8+ T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies.

Efficacy of nab­paclitaxel vs. Gemcitabine in combination with S­1 for advanced pancreatic cancer: A multicenter phase II randomized trial.

Patients with advanced pancreatic cancer (PC) need a cost-effective treatment regimen. The present study was designed to compare the efficacy and safety of nab-paclitaxel plus S-1 (AS) and gemcitabine plus S-1 (GS) regimens in patients with chemotherapy-naïve advanced PC. In this open-label, multicenter, randomized study named AvGmPC, eligible patients with chemotherapy-naïve advanced PC were randomly assigned (1:1) to receive AS (125 mg/m2 nab-paclitaxel, days 1 and 8; 80-120 mg S-1, days 1-14) or GS (1,000 mg/m2 gemcitabine, days 1 and 8; 80-120 mg S-1, days 1-14). The treatment was administered every 3 weeks until intolerable toxicity or disease progression occurred. The primary endpoint was progression-free survival (PFS). Between December 2018 and March 2022, 101 of 106 randomized patients were treated and evaluated for analysis (AS, n=49; GS, n=52). As of the data cutoff, the median follow-up time was 11.37 months [95% confidence interval (CI), 9.31-13.24]. The median PFS was 7.16 months (95% CI, 5.19-12.32) for patients treated with AS and 6.41 months (95% CI, 3.72-8.84) for patients treated with GS (HR=0.78; 95% CI, 0.51-1.21; P=0.264). The AS regimen showed a slightly improved overall survival (OS; 13.27 vs. 10.64 months) and a significantly improved ORR (44.90 vs. 15.38%; P=0.001) compared with the GS regimen. In the subgroup analyses, PFS and OS benefits were observed in patients treated with the AS regimen who had KRAS gene mutations and high C-reactive protein (CRP) levels (≥5 mg/l). The most common grade ≥3 adverse events were neutropenia, anemia and alopecia in the two groups. Thrombocytopenia occurred more frequently in the GS group than in the AS group. While the study did not meet the primary endpoint, the response benefit observed for AS may be suggestive of meaningful clinical activity in this population. In particular, promising survival benefits were observed in the subsets of patients with KRAS gene mutations and high CRP levels, which is encouraging and warrants further investigation. This trial was retrospectively registered as ChiCTR1900024588 on July 18, 2019.

Motion compensated structured low-rank reconstruction for 3D multi-shot EPI.

PURPOSE: The 3D multi-shot EPI imaging offers several benefits including higher SNR and high isotropic resolution compared to 2D single shot EPI. However, it suffers from shot-to-shot inconsistencies arising from physiologically induced phase variations and bulk motion. This work proposed a motion compensated structured low-rank (mcSLR) reconstruction method to address both issues for 3D multi-shot EPI. METHODS: Structured low-rank reconstruction has been successfully used in previous work to deal with inter-shot phase variations for 3D multi-shot EPI imaging. It circumvents the estimation of phase variations by reconstructing an individual image for each phase state which are then sum-of-squares combined, exploiting their linear interdependency encoded in structured low-rank constraints. However, structured low-rank constraints become less effective in the presence of inter-shot motion, which corrupts image magnitude consistency and invalidates the linear relationship between shots. Thus, this work jointly models inter-shot phase variations and motion corruptions by incorporating rigid motion compensation for structured low-rank reconstruction, where motion estimates are obtained in a fully data-driven way without relying on external hardware or imaging navigators. RESULTS: Simulation and in vivo experiments at 7T have demonstrated that the mcSLR method can effectively reduce image artifacts and improve the robustness of 3D multi-shot EPI, outperforming existing methods which only address inter-shot phase variations or motion, but not both. CONCLUSION: The proposed mcSLR reconstruction compensates for rigid motion, and thus improves the validity of structured low-rank constraints, resulting in improved robustness of 3D multi-shot EPI to both inter-shot motion and phase variations.

Dynamic field mapping and distortion correction using single-shot blip-rewound EPI and joint multi-echo reconstruction.

PURPOSE: To develop a method for dynamic ∆ B 0 $$ \Delta {B}_0 $$ mapping and distortion correction. METHODS: A blip-rewound EPI trajectory was developed to acquire multiple 2D EPI images in a single readout with an interleaved order, which allows a short TE difference. A joint multi-echo reconstruction was utilized to exploit the shared information between EPI images. The reconstructed images from each readout are combined to produce a final magnitude image. A ∆ B 0 $$ \Delta {B}_0 $$ map is calculated from the phase of these images for distortion correction. The efficacy of the proposed method is assessed with phantom and in vivo experiments. The performance of the proposed method in the presence of subject motion is also investigated. RESULTS: Compared to conventional multi-echo EPI, the proposed method allows dynamic ∆ B 0 $$ \Delta {B}_0 $$ mapping at matched resolution with a much shorter TR. Phantom and in vivo results show that the proposed method can provide a comparable magnitude image as conventional single-shot EPI. The ∆ B 0 $$ \Delta {B}_0 $$ maps calculated from the proposed method are consistent with conventional multi-echo EPI in the phantom experiment. For in vivo experiments, the proposed method provides a more accurate estimation of ∆ B 0 $$ \Delta {B}_0 $$ than conventional multi-echo EPI, which is prone to phase wrapping problems due to the long TE difference. In-vivo scan with subject motion shows the proposed dynamic field mapping method can improve the temporal stability of EPI time series compared to gradient echo (GRE) based static field mapping. CONCLUSION: The proposed method allows accurate dynamic ∆ B 0 $$ \Delta {B}_0 $$ mapping for robust distortion correction without compromising spatial or temporal resolution.

Tumor Microenvironment Responsive CD8+ T Cells and Myeloid-Derived Suppressor Cells to Trigger CD73 Inhibitor AB680-Based Synergistic Therapy for Pancreatic Cancer.

CD73 plays a critical role in the pathogenesis and immune escape in pancreatic ductal adenocarcinoma (PDAC). AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti-PD-1 therapy, for the treatment of PDAC. Nevertheless, the specific therapeutic efficacy and immunoregulation within the microenvironment of AB680 monotherapy in PDAC have yet to be fully elucidated. In this study, AB680 exhibits a significant effect in augmenting the infiltration of responsive CD8+ T cells and prolongs the survival in both subcutaneous and orthotopic murine PDAC models. In parallel, it also facilitates chemotaxis of myeloid-derived suppressor cells (MDSCs) by tumor-derived CXCL5 in an AMP-dependent manner, which may potentially contribute to enhanced immunosuppression. The concurrent administration of AB680 and PD-1 blockade, rather than gemcitabine, synergistically restrain tumor growth. Notably, gemcitabine weakened the efficacy of AB680, which is dependent on CD8+ T cells. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD-1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC.

Serum Interleukin-6 as a Biomarker for Early Prediction of Post-Operative Infectious Complications After Elective Pancreatectomy.

Background: To investigate whether interleukin (IL)-6 could predict the post-operative complications of elective pancreatectomy early. Patients and Methods: Overall, 122 patients who underwent elective pancreatectomy from June 2020 to May 2021 in our hospital were enrolled. Interleukin-6 was measured on the day before and at six hours after surgery, and on post-operative day one, three, and five. The associations between IL-6 level and post-operative complications were analyzed, and the predictive value of IL-6 for complications was assessed. Results: Sixty-three patients developed post-operative complications. Higher IL-6 was observed in patients with post-operative complications on post-operative day one, post-operative day three, and post-operative day five, with odd ratios of 1.43, 1.68, and 2.54 (p = 0.01, p = 0.01, and p = 0.01), respectively. These trends were also observed in patients with infectious complications preoperatively, on post-operative day one, post-operative day three, and post-operative day five, with ORs of 2.46, 1.95, 2.01, and 2.49 (p = 0.00, 0.00, 0.01, 0.00) respectively. Multivariate regression revealed that IL-6 is the only predictor for infectious complications on post-operative day one (p = 0.016). Based on the optimal cutoffs, pre-operative IL-6, IL-6 on post-operative day one and post-operative day three for predicting infectious complications yielded area under the curve (AUC) of 0.73, 0.70, and 0.70, with high negative predictive value of 82.7%, 92.2%, and of 91.3%, respectively. Conclusions: This study validated the early predictive value of IL-6 on infectious complications after pancreatectomy. Because of the performance of serum IL-6 in predicting infectious complications and high NPV, we endorse that IL-6 could be a potential biomarker for early prediction and antibiotic optimization after pancreatectomy.

The evolution and heterogeneity of neutrophils in cancers: origins, subsets, functions, orchestrations and clinical applications.

Neutrophils, the most prevalent innate immune cells in humans, have garnered significant attention in recent years due to their involvement in cancer progression. This comprehensive review aimed to elucidate the important roles and underlying mechanisms of neutrophils in cancer from the perspective of their whole life cycle, tracking them from development in the bone marrow to circulation and finally to the tumor microenvironment (TME). Based on an understanding of their heterogeneity, we described the relationship between abnormal neutrophils and clinical manifestations in cancer. Specifically, we explored the function, origin, and polarization of neutrophils within the TME. Furthermore, we also undertook an extensive analysis of the intricate relationship between neutrophils and clinical management, including neutrophil-based clinical treatment strategies. In conclusion, we firmly assert that directing future research endeavors towards comprehending the remarkable heterogeneity exhibited by neutrophils is of paramount importance.

A temperature-controlled cooling system for accurate quantitative post-mortem MRI.

PURPOSE: To develop a temperature-controlled cooling system to facilitate accurate quantitative post-mortem MRI and enable scanning of unfixed tissue. METHODS: A water cooling system was built and integrated with a 7T scanner to minimize temperature drift during MRI scans. The system was optimized for operational convenience and rapid deployment to ensure efficient workflow, which is critical for scanning unfixed post-mortem samples. The performance of the system was evaluated using a 7-h diffusion MRI protocol at 7T with a porcine tissue sample. Quantitative T1 , T2 , and ADC maps were interspersed with the diffusion scans at seven different time points to investigate the temperature dependence of MRI tissue parameters. The impact of temperature changes on biophysical model fitting of diffusion MRI data was investigated using simulation. RESULTS: Tissue T1 , T2 , and ADC values remained stable throughout the diffusion MRI scan using the developed cooling system, but varied substantially using a conventional scan setup without temperature control. The cooling system enabled accurate estimation of biophysical model parameters by stabilizing the tissue temperature throughout the diffusion scan, while the conventional setup showed evidence of significantly biased estimation. CONCLUSION: A temperature-controlled cooling system was developed to tackle the challenge of heating in post-mortem imaging, which shows potential to improve the accuracy and reliability of quantitative post-mortem imaging and enables long scans of unfixed tissue.

Additional adjuvant radiotherapy improves survival at 1 year after surgical treatment for pancreatic cancer patients with T4, N2 disease, positive resection margin, and receiving adjuvant chemotherapy.

Background: While adjuvant chemotherapy has been established as standard practice following radical resection of pancreatic ductal adenocarcinoma (PDAC), the role of adjuvant radiation therapy (RT) and which patients may benefit remains unclear. Methods: This retrospective study included PDAC patients who received pancreatic surgery from April 2012 to December 2019 in Zhongshan Hospital Fudan University. Patients with carcinoma in situ, distant metastasis, and without adjuvant chemotherapy were excluded. Cox proportional hazards modeling of survival were constructed to find potential prognostic factors. Propensity score matching (PSM) and exploratory subgroup analyses were used to create a balanced covariate distribution between groups and to investigate therapeutic effect of radiotherapy in certain subgroups. Results: A total of 399 patients were finally included, 93 of them receiving adjuvant chemoradiotherapy (C+R+) and 306 of them receiving chemotherapy only. Patients in C+R+ group were more likely to be male patients with T3-4 disease. Lymph node metastases was the only negative prognostic factor associated with overall survival (OS). Additional adjuvant RT was not associated with an OS benefit both before and after PSM. Surprisingly, a trend towards improved OS with RT among patients with either T4, N2 disease or R1 resection becomes significant in patients alive more than 1 year after surgery. Conclusion: Adjuvant RT was not associated with an OS benefit across all patients, though did show a possible OS benefit for the subgroup with T4N2 disease or R1 resection at 1 year after surgery.

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. METHODS: Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. RESULTS: The study enrolled a total of 1589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group [mean age, 64.0 (9.9) years; 766 (48.2%) were females and 823 (51.8%) were males]. All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 months, P =0.002) and CSS (33.0 vs. 27.0 months, P =0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P =0.003, HR=0.782; 95% CI, 0.667-0.917 for OS; P =0.004, HR=0.784; 95% CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. CONCLUSION: Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.

Sampling strategies and integrated reconstruction for reducing distortion and boundary slice aliasing in high-resolution 3D diffusion MRI.

PURPOSE: To develop a new method for high-fidelity, high-resolution 3D multi-slab diffusion MRI with minimal distortion and boundary slice aliasing. METHODS: Our method modifies 3D multi-slab imaging to integrate blip-reversed acquisitions for distortion correction and oversampling in the slice direction (kz ) for reducing boundary slice aliasing. Our aim is to achieve robust acceleration to keep the scan time the same as conventional 3D multi-slab acquisitions, in which data are acquired with a single direction of blip traversal and without kz -oversampling. We employ a two-stage reconstruction. In the first stage, the blip-up/down images are respectively reconstructed and analyzed to produce a field map for each diffusion direction. In the second stage, the blip-reversed data and the field map are incorporated into a joint reconstruction to produce images that are corrected for distortion and boundary slice aliasing. RESULTS: We conducted experiments at 7T in six healthy subjects. Stage 1 reconstruction produces images from highly under-sampled data (R = 7.2) with sufficient quality to provide accurate field map estimation. Stage 2 joint reconstruction substantially reduces distortion artifacts with comparable quality to fully-sampled blip-reversed results (2.4× scan time). Whole-brain in-vivo results acquired at 1.22 mm and 1.05 mm isotropic resolutions demonstrate improved anatomical fidelity compared to conventional 3D multi-slab imaging. Data demonstrate good reliability and reproducibility of the proposed method over multiple subjects. CONCLUSION: The proposed acquisition and reconstruction framework provide major reductions in distortion and boundary slice aliasing for 3D multi-slab diffusion MRI without increasing the scan time, which can potentially produce high-quality, high-resolution diffusion MRI.

Highly accelerated intracranial time-of-flight magnetic resonance angiography using wave-encoding.

PURPOSE: To develop an accelerated 3D intracranial time-of-flight (TOF) magnetic resonance angiography (MRA) sequence with wave-encoding (referred to as 3D wave-TOF) and to evaluate two variants: wave-controlled aliasing in parallel imaging (CAIPI) and compressed-sensing wave (CS-wave). METHODS: A wave-TOF sequence was implemented on a 3 T clinical scanner. Wave-encoded and Cartesian k-space datasets from six healthy volunteers were retrospectively and prospectively undersampled with 2D-CAIPI sampling and variable-density Poisson disk sampling. 2D-CAIPI, wave-CAIPI, standard CS, and CS-wave schemes were compared at various acceleration factors. Flow-related artifacts in wave-TOF were investigated, and a set of practicable wave parameters was developed. Quantitative analysis of wave-TOF and traditional Cartesian TOF MRA was performed by comparing the contrast-to-background ratio between the vessel and background tissue in source images, and the structural similarity index measure (SSIM) between the maximum intensity projection images from accelerated acquisitions and their respective fully sampled references. RESULTS: Flow-related artifacts caused by the wave-encoding gradients in wave-TOF were eliminated by properly chosen parameters. Images from wave-CAIPI and CS-wave acquisitions had a higher SNR and better-preserved contrast than traditional parallel imaging (PI) and CS methods. Maximum intensity projection images from wave-CAIPI and CS-wave acquisitions had a cleaner background, with vessels that were better depicted. Quantitative analyses indicated that wave-CAIPI had the highest contrast-to-background ratio, SSIM, and vessel-masked SSIM among the sampling schemes studied, followed by the CS-wave acquisition. CONCLUSION: 3D wave-TOF improves the capability of accelerated MRA and provides better image quality at higher acceleration factors compared to traditional PI- or CS-accelerated TOF, suggesting the potential use of wave-TOF in cerebrovascular disease.

Diffusion MRI data analysis assisted by deep learning synthesized anatomical images (DeepAnat).

Diffusion MRI is a useful neuroimaging tool for non-invasive mapping of human brain microstructure and structural connections. The analysis of diffusion MRI data often requires brain segmentation, including volumetric segmentation and cerebral cortical surfaces, from additional high-resolution T1-weighted (T1w) anatomical MRI data, which may be unacquired, corrupted by subject motion or hardware failure, or cannot be accurately co-registered to the diffusion data that are not corrected for susceptibility-induced geometric distortion. To address these challenges, this study proposes to synthesize high-quality T1w anatomical images directly from diffusion data using convolutional neural networks (CNNs) (entitled "DeepAnat"), including a U-Net and a hybrid generative adversarial network (GAN), and perform brain segmentation on synthesized T1w images or assist the co-registration using synthesized T1w images. The quantitative and systematic evaluations using data of 60 young subjects provided by the Human Connectome Project (HCP) show that the synthesized T1w images and results for brain segmentation and comprehensive diffusion analysis tasks are highly similar to those from native T1w data. The brain segmentation accuracy is slightly higher for the U-Net than the GAN. The efficacy of DeepAnat is further validated on a larger dataset of 300 more elderly subjects provided by the UK Biobank. Moreover, the U-Nets trained and validated on the HCP and UK Biobank data are shown to be highly generalizable to the diffusion data from Massachusetts General Hospital Connectome Diffusion Microstructure Dataset (MGH CDMD) acquired with different hardware systems and imaging protocols and therefore can be used directly without retraining or with fine-tuning for further improved performance. Finally, it is quantitatively demonstrated that the alignment between native T1w images and diffusion images uncorrected for geometric distortion assisted by synthesized T1w images substantially improves upon that by directly co-registering the diffusion and T1w images using the data of 20 subjects from MGH CDMD. In summary, our study demonstrates the benefits and practical feasibility of DeepAnat for assisting various diffusion MRI data analyses and supports its use in neuroscientific applications.

Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis.

BACKGROUND: The Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting. METHODS: Visual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA; ≤ 48 and > 48 letters); (2) baseline CRT (≤ 325 or > 325 µm); and (3) treatment response after three monthly initial injections: < or ≥ 5-letter gain in BCVA and reduction of < or ≥ 50 µm in CRT. RESULTS: Patient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (≤ 48 letters) and baseline CRT severity (> 325 µm) were predictors of maximum BCVA gains (9.6 ± 12.9 letters [95%CI: 6.3 to 12.9] and 5.1 ± 18.3 letters [95%CI: - 0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (- 127.6 ± 104.2 µm and - 104.2 ± 107.4 µm at Months 3 and 12, respectively; both P < 0.001). For the subgroup showing favourable treatment improvement with BCVA gains ≥ 5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5 ± 14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains < 5-letter subgroup nevertheless had stable BCVA (0.4 ± 12.1 letter gains) and CRT (- 41.9 ± 61.2 µm) at Month 12, respectively. In the subgroup with ≥ 50 µm CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the < 50 µm CRT reduction subgroup at Month 3 (5.0 ± 8.6 letter gains vs. 1.5 ± 11.6 letter gains, respectively; intergroup P = 0.005). CONCLUSION: Lower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.

Improving robustness of 3D multi-shot EPI by structured low-rank reconstruction of segmented CAIPI sampling for fMRI at 7T.

Three-dimensional (3D) encoding methods are increasingly being explored as alternatives to two-dimensional (2D) multi-slice acquisitions in fMRI, particularly in cases where high isotropic resolution is needed. 3D multi-shot EPI acquisition, as the workhorse of 3D fMRI imaging, is susceptible to physiological fluctuations which can induce inter-shot phase variations, and thus reducing the achievable tSNR, negating some of the benefit of 3D encoding. This issue can be particularly problematic at ultra-high fields like 7T, which have more severe off-resonance effects. In this work, we aim to improve the temporal stability of 3D multi-shot EPI at 7T by improving its robustness to inter-shot phase variations. We presented a 3D segmented CAIPI sampling trajectory ("seg-CAIPI") and an improved reconstruction method based on Hankel structured low-rank matrix recovery. Simulation and in-vivo results demonstrate that the combination of the seg-CAIPI sampling scheme and the proposed structured low-rank reconstruction is a promising way to effectively reduce the unwanted temporal variance induced by inter-shot physiological fluctuations, and thus improve the robustness of 3D multi-shot EPI for fMRI.

Circulating cytokines allow for identification of malignant intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancers, requiring active surgical intervention during cancer development. However, the current criteria for predicting malignant IPMNs remain challenging and limited. Hence, this study aimed to assess the discriminatory performance of circulating cytokines, including TNF-α, IL-2R, IL-6, and IL-8, then build a novel predictive model to improve the diagnostic accuracy. METHOD: A total of 131 retrospective (from March 2016 to December 2019) and 53 prospective (from March 2020 to January 2021) patients who were histologically confirmed as IPMNs were consecutively collected and analyzed. RESULT: The circulating levels of TNF-α, IL-2R, IL-6, and IL-8 were significantly elevated in malignant IPMNs, and were verified as independent factors for malignant IPMNs (p < 0.05). Then, a novel score, the circulating cytokine score (CCS), was calculated and demonstrated as an independent predictive indicator with a higher area under the curve (AUC) than each cytokine alone (p < 0.001). Besides the CCS, two high-risk stigmata features, the presence of solid component (PSC), and main pancreatic duct (MPD) dilation ≥10 mm were also demonstrated as independent indicators for predicting malignant IPMNs. Finally, a novel nomogram incorporating the CCS and these two high-risk stigmata features presented a remarkable diagnostic performance, both in the training and validation cohorts with AUCs of 0.928 and 0.873, respectively. CONCLUSION: The CCS can be considered a novel independent predictive indicator for malignant IPMNs. Additionally, the formulated nomogram model integrating the CCS, PSC, and MPD ≥10 mm can be a valuable and promising tool for predicting the malignant transformation of IPMNs during long-term follow-ups to assist in timely and accurate surgical decisions.