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Purpose: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Methods: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Results: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application.Conclusion: Periprosthetic loosening is a major complication after total hip and knee arthroplasty. Early and accurate diagnosis is essential to choose the right therapeutic path and to avoid further complications. The aim of the study was to evaluate the diagnostic performance of 68Gallium-Zoledronate ([68Ga]Ga-DOTAZol) PET/CT in detecting periprosthetic loosening in total hip (THA) and total knee arthroplasty (TKA).This retrospective study included 26 patients with painful prosthesis (THA n = 17; TKA n = 16) and clinical suspicion of periprosthetic loosening, but without a confirmed diagnosis. Patients underwent [68Ga]Ga-DOTAZol PET/CT at least one year post-implantation. Diagnosis was confirmed through revision surgery or long-term clinical follow-up, with an observation period of at least 6 months. The analysis included both an assessment of the prosthesis as a unit and a separate evaluation of the individual components. Statistical analysis involved calculating sensitivity, specificity and accuracy using SPSS.Overall, a sensitivity of 77.8%, a specificity of 95.8% and an accuracy of 90.9% were found for detecting periprosthetic loosening, when considering the prosthesis as a unit. Individual component analyses showed a sensitivity of 71.4% and specificity of 96.2%.The use of [68Ga]Ga-DOTAZol PET/CT in periprosthetic loosening is a remarkable diagnostic tool and a promising approach. In comparison to established radionuclide tracers, 68Gallium-Zoledronate offers notable advantages due to its availability via 68Ge/68Ga-generators, improving its potential for clinical application. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that they have no conflict of interest.

Objective: To assess whether arterial spin labeling perfusion images of healthy controls can enhance ictal single-photon emission computed tomography analysis and whether the acquisition of the interictal image can be omitted., Methods: We developed 2 pipelines: The first uses ictal and interictal images and compares these to single-photon emission computed tomography and arterial spin labeling of healthy controls. The second pipeline uses only the ictal image and the analogous healthy controls. Both pipelines were compared to the gold standard analysis and evaluated on data of individuals with epilepsy who underwent ictal single-photon emission computed tomography imaging during presurgical evaluation between 2010 and 2022. Fifty healthy controls prospectively underwent arterial spin labeling imaging. The correspondence between the detected hyperperfusion and the postoperative resection cavity or the presumably affected lobe was assessed using Dice score and mean Euclidean distance. Additionally, the outcomes of the pipelines were automatically assigned to 1 of 5 concordance categories., Results: Inclusion criteria were met by 43 individuals who underwent epilepsy surgery and by 73 non-surgical individuals with epilepsy. Compared to the gold standard analysis, both pipelines resulted in significantly higher Dice scores and lower mean distances (p < 0.05). The combination of both provided localizing results in 85/116 cases, compared to 54/116 generated by the current gold standard analysis and the ictal image alone produced localizing results in 60/116 (52%) cases., Interpretation: We propose a new ictal single-photon emission computed tomography protocol; it finds relevantly more ictal hyperperfusion, and halves the radiation dose in about half of the individuals. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Subjective cognitive decline (SCD) in amyloid-positive (Aβ+) individuals was proposed as a clinical indicator of Stage 2 in the Alzheimer's disease (AD) continuum, but this requires further validation across cultures, measures, and recruitment strategies., Methods: Eight hundred twenty-one participants from SILCODE and DELCODE cohorts, including normal controls (NC) and individuals with SCD recruited from the community or from memory clinics, underwent neuropsychological assessments over up to 6 years. Amyloid positivity was derived from positron emission tomography or plasma biomarkers. Global cognitive change was analyzed using linear mixed-effects models., Results: In the combined and stratified cohorts, Aβ+ participants with SCD showed steeper cognitive decline or diminished practice effects compared with NC or Aβ- participants with SCD. These findings were confirmed using different operationalizations of SCD and amyloid positivity, and across different SCD recruitment settings., Discussion: Aβ+ individuals with SCD in German and Chinese populations showed greater global cognitive decline and could be targeted for interventional trials., Highlights: SCD in amyloid-positive (Aβ+) participants predicts a steeper cognitive decline. This finding does not rely on specific SCD or amyloid operationalization. This finding is not specific to SCD patients recruited from memory clinics. This finding is valid in both German and Chinese populations. Aβ+ older adults with SCD could be a target population for interventional trials., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Pancreatic adenocarcinoma (PaC) still has a dismal prognosis, and despite medical advances, a bleak 5-year survival rate of only 8%, largely due to late diagnosis and limited curative surgical options for most patients. Frontline palliative treatment shows some survival advantages. However, the high disease mortality is accompanied by high morbidity including cancer-related pain and additional symptoms, which strongly impair patients' quality of life (QOL). At present, there is no established strategy for local therapy for PaC primarily aiming to manage local tumor growth and alleviate associated symptoms, particularly pain. In recent years, non-invasive high-intensity focused ultrasound (HIFU) has shown promising results in reducing cancer pain and tumor mass, improving patients' QOL with few side effects., Study Design: This is the first randomized controlled trial worldwide including 40 patients with inoperable pancreatic adenocarcinoma randomized into two groups: group A undergoing standard chemotherapy; and group B undergoing standard chemotherapy plus local HIFU treatment. This study aims to establish a robust evidence base by examining the feasibility, safety, and efficacy of US-guided HIFU in combination with standard palliative systemic therapy for unresectable PaC. Primary endpoint assessments will focus on parameters including safety issues (phase I), and local response rates (phase II).

Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76-11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11-9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10-13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results., (© 2024. The Author(s).)

Background: Prostate cancer (PCa) diagnosis and staging have evolved with the advent of 68Ga-Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This study investigates the role of complementary systematic biopsies (SB) during PSMA-PET/CT-guided targeted prostate biopsies (PET-TB) for PCa detection, grading, and distribution. We address the uncertainty surrounding the necessity of SB in conjunction with PET-TB., Methods: We analyzed PCa grading and distribution in 30 men who underwent PET-TB and SB because of contraindication to magnetic resonance imaging or high clinical suspicion of PCa. Tumor distribution was assessed in relation to the PET-highlighted lesions. Standardized reporting schemes, encompassing SUV max , PRIMARY score, and miTNM classification, were evaluated., Results: 80% of patients were diagnosed with PCa, with 70% classified as clinically significant (csPCa). SB detected more csPCa cases than PET-TB, but the differences were not statistically significant. Discordant results were observed in 25% of cases, where SB outperformed PET-TB. Spatial analysis revealed that tumor-bearing cores from SB were often located in close proximity to the PET-highlighted region. Reporting schemes showed potential for csPCa detection with significantly increased SUV max in csPCA patients. Subsequent follow-up data underscored the importance of SB in precise PCa grading and staging., Conclusions: While PET-TB can simplify prostate biopsy and reduce invasiveness by core number, SB cannot be omitted yet due to potential PET-TB targeting errors. Factors such as limited spatial resolution and fusion inaccuracies contribute to the need for SB. Standardization in reporting schemes currently cannot compensate for targeting errors highlighting the need for refinement., (© 2024 The Authors. The Prostate published by Wiley Periodicals LLC.)

Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern., Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes., Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L&#95;CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation., Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Li, Sharma, Hoffmann, Skowasch, Essler, Weiher and Schmidt-Wolf.)

Purpose: Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer., Material and Methods: MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections (n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay., Results: MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections (p < 0.01) and in TMA sections (p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy (p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001)., Conclusion: The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities., (© 2024. The Author(s).)

Purpose: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) represents a safe and effective non-invasive thermoablative technique for managing inoperable pancreatic cancer. This treatment method significantly alleviates disease-related symptoms and reduces pancreatic tumor volume. However, the current body of evidence is constrained by a lack of randomized controlled trials. The utilization of USgHIFU is primarily indicated for patients with unresectable, locally advanced, or metastatic pancreatic cancer, particularly those experiencing symptoms due to a locally advanced primary tumor. Methods: This collaborative consensus paper, involving European and Chinese HIFU centers treating pancreatic cancer, delineates criteria for patient selection, focusing on those most likely to benefit from USgHIFU treatment. Consideration is given to endpoints encompassing symptom alleviation, local response rates, other oncological outcomes, as well as overall and progression-free survival. Additionally, this paper defines relevant contraindications, side effects, and complications associated with USgHIFU. The publication also explores the feasibility and role of USgHIFU within the context of palliative care, including standard systemic chemotherapy. Results: The non-invasive local treatment of advanced pancreatic cancer using HIFU should be regarded as an adjunctive option alongside systemic chemotherapy or best supportive care for managing this aggressive disease. Based on the ability of USgHIFU therapy to mitigate pain and reduce primary tumor volume, it should be considered as a complementary therapy for symptomatic patients with inoperable pancreatic cancer and as a potential means of tumor debulking. The underutilized yet promising USgHIFU exhibits the potential to enhance patients' quality of life by alleviating cancer-related pain. Experts in the field should evaluate this treatment option be evaluated by experts in this field, with this consensus paper potentially serving as a guiding resource for the medical community. Conclusions: US-guided HIFU for advanced pancreatic cancer addresses treatment goals, available options, success rates, and limitations. As a non-invasive, effective local therapy, complementary to chemotherapy and best supportive care, it plays a pivotal role in pain relief, reducing of tumor volume, and potentially improving survival rates.