Osteoimmunology of Spondyloarthritis

: The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. we summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA

Health technology assessment for PSMA-PET: striving towards a cost-effective management of prostate cancer

Introduction: To summarize recent analyses on the economic aspects regarding the use of PSMA-PET in prostate cancer and to evaluate the cost-effective management of patients referred to this new generation imaging to stage the disease. Methods: A comprehensive search was performed based on SCOPUS and PubMed databases to evaluate studies reporting about cost analysis in PSMA-PET. Results: Preliminary data regarding the cost-effective management of prostate cancer patients investigated with PSMA-PET have been found. These studies both explored the pre-surgery and the biochemical recurrent setting. Furthermore, separate analyses about the use hybrid PET/CT and PET/MRI scanners have been reported. Conclusion: PSMA-PET has the potential to save time and reduce costs from a patient and health-care perspective, by providing a more accurate disease staging and leading to more effective, personalized, imaging-guided approach

Comparison of Digital versus Analog ⁶⁸Ga-PSMA-11 PET/CT Performance in Hormone-Sensitive Prostate Cancer Patients with Early Biochemical Recurrence or Persistence after Radical Treatment

The aim of this study was to investigate whether the favorable characteristics of novel digital PET/CT (dPET) scanners compared to analog systems (aPET) could translate into an improved disease localization in prostate cancer (PCa) patients with early biochemical recurrence/persistence (BCR/BCP). A retrospective analysis was conducted on 440 consecutive analog (n = 311) or digital (n = 129) 68Ga-PSMA-11 PET/CT scans performed in hormone-sensitive ADT-free PCa patients with early-BCR/BCP (PSA at PET ≤ 2.0 ng/mL), previously treated with radical intent (radical-prostatectomy/radiotherapy). dPET showed a higher positivity rate compared to aPET (48.8% [63/129] vs. 37.3% [116/311], p = 0.03), despite the slightly lower median PSA value of the dPET cohort (0.33 [IQR: 0.26–0.61] vs. 0.55 [IQR: 0.40–0.85] ng/mL, p p = 0.03) and 0.5–1.0 ng/mL (63.2% [24/38] vs. 40.8% [53/130], p = 0.02), but not for PSA ≥ 1.0 ng/mL. dPET detected a higher per patient median number of pathologic findings (PSMA-RADS ≥ 3) and multi-metastatic cases (>3 lesions) among N1/M1-positive scans (21.7% [10/46] vs. 8.6% [9/105], p = 0.03). Moreover, the proportion of uncertain findings among pathological lesions was significantly lower for dPET than aPET (24.4% [39/160] vs. 38.5% [60/156], p = 0.008). Overall, 68Ga-PSMA-11 dPET showed a better performance compared to aPET, resulting in a higher scan-positivity rate, a higher number of detected pathological lesions, and a lower rate of uncertain findings

Machine Learning CT-Based Automatic Nodal Segmentation and PET Semi-Quantification of Intraoperative ⁶⁸Ga-PSMA-11 PET/CT Images in High-Risk Prostate Cancer: A Pilot Study

High-resolution intraoperative PET/CT specimen imaging, coupled with prostate-specific membrane antigen (PSMA) molecular targeting, holds great potential for the rapid ex vivo identification of disease localizations in high-risk prostate cancer patients undergoing surgery. However, the accurate analysis of radiotracer uptake would require time-consuming manual volumetric segmentation of 3D images. The aim of this study was to test the feasibility of using machine learning to perform automatic nodal segmentation of intraoperative 68Ga-PSMA-11 PET/CT specimen images. Six (n = 6) lymph-nodal specimens were imaged in the operating room after an e.v. injection of 2.1 MBq/kg of 68Ga-PSMA-11. A machine learning-based approach for automatic lymph-nodal segmentation was developed using only open-source Python libraries (Scikit-learn, SciPy, Scikit-image). The implementation of a k-means clustering algorithm (n = 3 clusters) allowed to identify lymph-nodal structures by leveraging differences in tissue density. Refinement of the segmentation masks was performed using morphological operations and 2D/3D-features filtering. Compared to manual segmentation (ITK-SNAP v4.0.1), the automatic segmentation model showed promising results in terms of weighted average precision (97–99%), recall (68–81%), Dice coefficient (80–88%) and Jaccard index (67–79%). Finally, the ML-based segmentation masks allowed to automatically compute semi-quantitative PET metrics (i.e., SUVmax), thus holding promise for facilitating the semi-quantitative analysis of PET/CT images in the operating room

Artificial Intelligence in Breast Cancer: A Systematic Review on PET Imaging Clinical Applications.

BACKGROUND 18F-FDG PET/CT imaging represents the most important functional imaging method in oncology. European Society of Medical Oncology and the National Comprehensive Cancer Network guidelines defined a crucial role of 18F-FDG PET/CT imaging for local/locally advanced breast cancer. The application of artificial intelligence on PET images might potentially contributes in the field of precision medicine. OBJECTIVE This review aims to summarize the clinical indications and limitations of PET imaging for comprehensive artificial intelligence in relation to breast cancer subtype, hormone receptor status, proliferation rate, and lymphonodal (LN)/distant metastatic spread, based on recent literature. METHODS A literature search of the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases was carried out, searching for articles on the use of artificial intelligence and PET in breast tumors. The search was updated from January 2010 to October 2021 and was limited to original articles published in English and about humans. A combination of the search terms "artificial intelligence", "breast cancer", "breast tumor", "PET", "Positron emission tomography", "PET/CT", "PET/MRI", "radiomic","texture analysis", "machine learning", "deep learning" was used. RESULTS Twenty-three articles were selected following the PRISMA criteria from 139 records obtained from the Pubmed/Scopus/Google Scholar/Cochrane/EMBASE databases according to our research strategy. The QUADAS of 30 full-text articles assessed reported seven articles that were excluded for not being relevant to population and outcomes and/or for lower level of evidence. The majority of papers were at low risk of bias and applicability. The articles were divided per topic, such as the value of PET in the staging and re-staging of breast cancer patients, including new radiopharmaceuticals and simultaneous PET/MRI. CONCLUSION Despite the current role of AI in this field remains still undefined, several applications for PET/CT imaging are under development, with some preliminary interesting results particularly focused on the staging phase that might be clinically translated after further validation studies

Precision radiotherapy by SPECT lung functional imaging in NSCLC

Background: Single Photon Emission Computed Tomography (SPECT) could be used to avoid the non-affected perfusion areas in patients with non-small-cell lung cancer (NSCLC) and to potentially reduce lung toxicity. The aim of this study is to compare dosimetric differences between two different 3D-conformal treatment plans, with and without CT/SPECT contribution. Methods: Simulation Computed tomography (CT) scans were accurately co-registered with SPECT scans and three different areas, based on SPECT intensity perfusion, were contoured: low perfusion (LP), medium perfusion (MP) and high perfusion (HP). Two different 3D-conformal plans, with co-planar and nonco-planar fields, were generated; one without SPECT information (anatomic plan), and one using the perfusion area identified with functional imaging (functional plan). Results: 9 patients were planned and a total of 18 plans were available for analysis. Anatomical and functional plans resulted in comparable planning target volume (PTV) coverage. In the functional plans, a significant reduction of dose in high perfusion areas was reported. The reduction of HP-V20 Gy values ranged from 15% to 8% (p = 0.046), the ipsiHP-V20 Gy from 38% to 22% (p = 0.028) and ipsiHP-Dmean reduction from 16 Gy to 12 Gy (p = 0.039). No significant differences in other organs at risk (OARs) metrics were reported between anatomical and functional plans. Conclusions: Despite the few cases reported, the strength of our study lies in the reported benefit of functional lung information in 3D conformal radiation planning, without compromising target coverage or worsening dose distribution to the OARs. There is an urgent need for prospective clinical and randomized trials in order to define the role of lung functional imaging in reducing toxicity in clinical practice

Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study

<div><p>The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn’t come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.</p></div

T helper subsets in eRA patients and healthy controls.

<p>Dot plots show CD4+/IFNγ+ (panel A), CD4+/IL4+ (panel B), CD4+/IL17A+ (panel C), CD4+/IL17A+/IFNγ+ (panel D) and Tregs (panel E);mean and SD are shown, p values were calculated by Mann-Whitney test and are displayed.</p