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Cell Reports Jun 2024Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched...
Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors. With longitudinal analysis, we identified an "immune-striving" tumor microenvironment marked by peri-tumor lymphoid aggregates and low infiltration of T cells in the tumor and the emergence of MITFSPARCL1 and CENPF melanoma subclones after therapy. The enrichment of B cell-associated signatures in the molecular composition of lymphoid aggregates was associated with better survival. These findings provide further insights into the establishment of microenvironmental cell interactions and molecular composition of spatial structures that could inform therapeutic intervention.
PubMed: 38944836
DOI: 10.1016/j.celrep.2024.114392 -
Journal of Vascular and Interventional... Jun 2024To Describe 6-Month safety, efficacy and multimodal imageability after imageable glass Yttrium-90 radioembolization for unresectable Hepatocellular Carcinoma (HCC) in a...
PURPOSE
To Describe 6-Month safety, efficacy and multimodal imageability after imageable glass Yttrium-90 radioembolization for unresectable Hepatocellular Carcinoma (HCC) in a First-in Human Trial METHODS: Eye90 microspheres® (Eye90), an FDA Breakthrough Designated Device, are glass radiopaque Y-90 microspheres visible on CT and SPECT/CT. Six subjects with unresectable HCC underwent selective (≤ 2 segments) Eye90 treatment in a prospective open-label pilot trial. Key inclusion criteria included liver only HCC, ECOG ≤ 1, total lesion length ≤ 9 cm and Child-Pugh A. Prospective partition dosimetry was utilized. Safety, biochemistry, toxicity, adverse events (AE), multimodal imageability on CT and SPECT/CT and 3 and 6-month MRI local modified RECIST (mRECIST) response was evaluated.
RESULTS
6 subjects with HCC (7 lesions) were treated with Eye90 and followed to 180 days. Administration success was 100%. Eye90 CT radiopacity distribution correlated with SPECT/CT. Target lesion complete response was observed in 3 of 6 subjects (50%) and partial response in 2 (33.3%). Two subjects could not be assessed at 180 days. At 180 days, target lesion complete response was maintained in 3 subjects (50%) and partial response in 1 (16.7%). All subjects reported AEs, and 5 reported AEs related to treatment. There were no treatment related serious AEs.
CONCLUSIONS
Eye90 was safe and effective in six subjects with unresectable HCC up to 6 months. Eye90 was imageable via CT and SPECT/CT with correlation between CT radiopacity and SPECT/CT radioactivity distribution. Eye90 provided previously unavailable CT based tumor targeting information.
PubMed: 38944236
DOI: 10.1016/j.jvir.2024.06.023 -
Nigerian Journal of Clinical Practice Jun 2024Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in...
The Prognostic Significance of Tumor SUVmax Value in Pre- and Post-Chemoradiotherapy 18F-FDG PET/CT Imaging in Patients with Localized and Advanced Head and Neck Squamous Cell Carcinoma.
BACKGROUND
Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in patients with head and neck squamous cell carcinoma (HNSCC).
AIM
The aim of the study was to investigate the prognostic value of pre- and post-treatment maximum standardized uptake values (SUVmax) in 18F-FDG PET/CT imaging for predicting mortality in patients with HNSCC, as well as its prognostic value in terms of disease progression, overall survival (OS), and progression-free survival (PFS).
METHODS
This retrospective study included 37 patients with a histopathological diagnosis of HNSCCs between 2015 and 2018. In patients with HNSCC, the first 18F-FDG PET/CT imaging was performed for pre-treatment staging, and the second imaging was performed to evaluate post-treatment response. In these imaging studies, SUVmax values of the primary tumor before and after treatment were determined. After the second imaging, patients were re-evaluated and followed up. ROC analysis was used to determine the predictive value of 18F-FDG PET/CT SUVmax parameters in terms of death and progression, and Cox regression analysis was used to investigate the prognostic value in terms of OS and PFS.
RESULTS
Cut-off value 15 for SUVmax1 (pre-treatment) had a significant predictive value for mortality (P = 0.02). Cut-off value 3.1 for SUVmax2 (post-treatment) had a significant predictive value for progression (P = 0.024). In univariate analysis, both SUVmax1 and SUVmax2 values were significant prognostic factors for OS (P = 0.047, P = 0.004). However, for PFS, only the SUVmax2 value was a significant prognostic factor (P = 0.001).
CONCLUSION
SUVmax1 value of the primary tumor at diagnosis in HNSCC patients has a predictive value for mortality and a prognostic value for OS. However, the SUVmax2 value in the primary tumor after treatment is a predictive factor for progression and a prognostic factor for both OS and PFS.
Topics: Humans; Fluorodeoxyglucose F18; Male; Positron Emission Tomography Computed Tomography; Female; Middle Aged; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Prognosis; Head and Neck Neoplasms; Aged; Chemoradiotherapy; Adult; Radiopharmaceuticals; Predictive Value of Tests; Disease Progression
PubMed: 38943299
DOI: 10.4103/njcp.njcp_856_23 -
BMC Cardiovascular Disorders Jun 2024The purpose of this study was to review echocardiography-based diagnosis of persistent fifth aortic arch (PFAA) in children.
BACKGROUND
The purpose of this study was to review echocardiography-based diagnosis of persistent fifth aortic arch (PFAA) in children.
METHODS
From January 2015 to December 2022, we retrospectively analyzed the echocardiographic findings and the relevant clinical data during follow-up of patients with PFAA who were treated in the Third Affiliated Hospital of Zhengzhou University. The diagnosis was confirmed by computed tomography angiography or surgery.
RESULTS
Seven PFAA cases included two Weinberg type A and five Weinberg type B. The anatomical details of PFAA were assessed using a combination of the long-axis view of the left ventricular outflow tract (from the left high parasternal window) and the long-axis view of the aortic arch (from the suprasternal window). In Weinberg type A, the distal fifth and fourth aortic arches were connected to the descending aorta, which was associated with aortic coarctation. In Weinberg type B, the upper arch of the fourth aorta was interrupted, and only the lower arch of the fifth aorta was connected to the descending aorta. Surgical repair of PFAA was indicated in five patients with blood flow disruption, among which four had good postoperative results and one refused surgery. Two patients with unobstructed PFAA blood flow required follow-up rather than surgery.
CONCLUSIONS
It is feasible to diagnose PFAA by echocardiography. Combined application of the high parasternal left ventricular outflow tract view and the suprasternal aortic arch view can improve timely detection of different types of PFAA in children.
Topics: Humans; Aorta, Thoracic; Retrospective Studies; Male; Female; Computed Tomography Angiography; Infant; Predictive Value of Tests; Child, Preschool; Aortography; Child; China; Aortic Coarctation; Treatment Outcome; Age Factors; Reproducibility of Results; Echocardiography
PubMed: 38943106
DOI: 10.1186/s12872-024-03999-5 -
Nature Communications Jun 2024Desert locust plagues threaten the food security of millions. Central to their formation is crowding-induced plasticity, with social phenotypes changing from cryptic...
Desert locust plagues threaten the food security of millions. Central to their formation is crowding-induced plasticity, with social phenotypes changing from cryptic (solitarious) to swarming (gregarious). Here, we elucidate the implications of this transition on foraging decisions and corresponding neural circuits. We use behavioral experiments and Bayesian modeling to decompose the multi-modal facets of foraging, revealing olfactory social cues as critical. To this end, we investigate how corresponding odors are encoded in the locust olfactory system using in-vivo calcium imaging. We discover crowding-dependent synergistic interactions between food-related and social odors distributed across stable combinatorial response maps. The observed synergy was specific to the gregarious phase and manifested in distinct odor response motifs. Our results suggest a crowding-induced modulation of the locust olfactory system that enhances food detection in swarms. Overall, we demonstrate how linking sensory adaptations to behaviorally relevant tasks can improve our understanding of social modulation in non-model organisms.
Topics: Animals; Grasshoppers; Odorants; Bayes Theorem; Social Behavior; Smell; Behavior, Animal; Crowding; Feeding Behavior; Olfactory Perception; Male; Female; Cues
PubMed: 38942759
DOI: 10.1038/s41467-024-49719-7 -
Korean Journal of Radiology Jul 2024To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT variables to...
Predicting Recurrence-Free Survival After Upfront Surgery in Resectable Pancreatic Ductal Adenocarcinoma: A Preoperative Risk Score Based on CA 19-9, CT, and F-FDG PET/CT.
OBJECTIVE
To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC).
MATERIALS AND METHODS
Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage.
RESULTS
A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; = 0.06), suspicious regional lymph nodes (HR, 1.43; = 0.02), possible distant metastasis on F-FDG PET/CT (HR, 2.32; = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; = 0.17).
CONCLUSION
The proposed risk score based on preoperative CA 19-9, CT, and F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.
Topics: Humans; Male; Fluorodeoxyglucose F18; Female; Positron Emission Tomography Computed Tomography; Middle Aged; Carcinoma, Pancreatic Ductal; Aged; Pancreatic Neoplasms; Retrospective Studies; Radiopharmaceuticals; CA-19-9 Antigen; Tomography, X-Ray Computed; Neoplasm Recurrence, Local; Risk Assessment; Disease-Free Survival; Predictive Value of Tests
PubMed: 38942458
DOI: 10.3348/kjr.2023.1235 -
Biological Psychiatry Jun 2024Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin-sensitive...
BACKGROUND
Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin-sensitive MRI (NM-MRI) provides a marker of long-term dopamine function. We examined if midbrain NM-MRI contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia relative to controls and if this correlated with dopamine synthesis capacity.
METHODS
N=154 participants (n=74 individuals with schizophrenia and n=80 healthy controls) underwent NM-MRI of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n=38) also received [18F]-DOPA PET to measure dopamine synthesis capacity (K) in the SN-VTA and striatum.
RESULTS
SN-VTA NM-CNR was significantly higher in patients with schizophrenia relative to controls (effect size=0.38, p=0.019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA K positively correlated with SN-VTA NM-CNR (r=0.44, p=0.005) and striatal K (r=0.71, p<0.001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal K (r=0.53, p=0.005) and that this relationship appeared strongest between the ventral SN-VTA and associative striatum in schizophrenia.
CONCLUSIONS
Our results suggest that neuromelanin levels are higher in patients with schizophrenia relative to controls, particularly in midbrain regions that project to parts of the striatum which receive innervation from the limbic and association cortices. The direct relationship between measures of neuromelanin and dopamine synthesis suggests that these aspects of schizophrenia pathophysiology are linked. Our findings highlight specific mesostriatal circuits as the loci of dopamine dysfunction in schizophrenia and, thus, potential therapeutic targets.
PubMed: 38942349
DOI: 10.1016/j.biopsych.2024.06.013 -
Survey of Ophthalmology Jun 2024Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and... (Review)
Review
Diabetic macular edema (DME), defined as retinal thickening near, or involving the fovea caused by fluid accumulation in the retina, can lead to vision impairment and blindness in patients with diabetes. Current knowledge of retina anatomy and function and DME pathophysiology has taken great advantage of the availability of several techniques for visualizing the retina. Combining these techniques in a multimodal imaging approach to DME is recommended to improve diagnosis and to guide treatment decisions. We review the recent literature about the following retinal imaging technologies: optical coherence tomography (OCT), OCT angiography (OCTA), wide-field and ultrawide-field techniques applied to fundus photography, fluorescein angiography, and OCTA. The emphasis will be on characteristic DME features identified by these imaging technologies and their potential or established role as diagnostic, prognostic, or predictive biomarkers. The role of artificial intelligence in the assessment and interpretation of retina images is also discussed.
PubMed: 38942124
DOI: 10.1016/j.survophthal.2024.06.006 -
The Lancet. Diabetes & Endocrinology Jun 2024Osteoporotic fractures are a major health challenge in older adults. Despite the availability of safe and effective therapies for osteoporosis, these therapies are... (Review)
Review
Osteoporotic fractures are a major health challenge in older adults. Despite the availability of safe and effective therapies for osteoporosis, these therapies are underused in individuals at high risk for fracture, calling for better case-finding and fracture risk assessment strategies. Artificial intelligence (AI) and machine learning (ML) hold promise for enhancing identification of individuals at high risk for fracture by distilling useful features from high-dimensional data derived from medical records, imaging, and wearable devices. AI-ML could enable automated opportunistic screening for vertebral fractures and osteoporosis, home-based monitoring and intervention targeting lifestyle factors, and integration of multimodal features to leverage fracture prediction, ultimately aiding improved fracture risk assessment and individualised treatment. Optimism must be balanced with consideration for the explainability of AI-ML models, biases (including information inequity in numerically under-represented populations), model limitations, and net clinical benefit and workload impact. Clinical integration of AI-ML algorithms has the potential to transform osteoporosis management, offering a more personalised approach to reduce the burden of osteoporotic fractures.
PubMed: 38942044
DOI: 10.1016/S2213-8587(24)00153-0 -
British Journal of Hospital Medicine... Jun 2024Breast leukaemia (BL) is a rare breast malignancy that is treated differently from other malignant conditions. However, it is easily confused with other conditions;...
Breast leukaemia (BL) is a rare breast malignancy that is treated differently from other malignant conditions. However, it is easily confused with other conditions; therefore, how to accurately diagnose is crucial. We retrospectively analysed the imaging findings of 13 patients to provide a diagnostic reference. From January 2015 to April 2023, 13 patients with BL confirmed by biopsy who underwent imaging in Peking University People's hospital were retrospectively analysed. The imaging findings obtained via ultrasound (US), mammography (MMG), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) were analysed, and the detection rates of these methods for diagnosing BL were compared. Twenty-nine lesions were detected in the 13 patients. These patients presented with palpable masses or breast swelling several months after treatment for leukaemia, mainly involving the bilateral breasts. Ultrasonography was performed for 13 patients, and all lesions were detected. Most of the identified masses were hypoechoic and had indistinct boundaries, irregular shapes, no enhancement of the posterior echo, and no abundant blood flow. MMG was performed for five patients, revealing breast masses, architectural distortion, and no abnormalities. MRI was performed for four patients, and all lesions were detected; most of the lesions were hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging and diffusion-weighted imaging, with a decreased apparent diffusion coefficient and inhomogeneous enhancement. The enhancement curves were mostly inflow patterns. PET/CT was performed for four patients; two patients had hypermetabolism, and the other two had no obvious radioactive uptake. Compared to MMG and PET/CT, US and MRI have higher detection rates. Furthermore, compared to MRI, US is inexpensive, convenient and efficient; therefore, it should be the first choice for diagnosing BL.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Adult; Retrospective Studies; Positron Emission Tomography Computed Tomography; Magnetic Resonance Imaging; Mammography; Ultrasonography, Mammary; Leukemia; Aged
PubMed: 38941971
DOI: 10.12968/hmed.2024.0101