Individual Lesions Research Articles

Organ-specific responses to nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma: A multicenter, retrospective study.

543 Background: The Check-Mate 9DW trial demonstrated that combining ipilimumab with nivolumab (Ipi/Nivo) improved survival outcomes compared with sorafenib or lenvatinib in advanced hepatocellular carcinoma (aHCC). Accumulated evidence suggests that immune checkpoint inhibitor (ICI) monotherapy elicits limited intrahepatic responses in patients with aHCC. Here, we aimed to examine the organ-specific objective response rate (OSORR) of Ipi/Nivo compared with that of nivolumab monotherapy (Nivo) and to evaluate the OSORR of Ipi/Nivo based on the prior use of ICI treatment. Methods: We conducted a retrospective assessment of 69 Ipi/Nivo-treated patients and 164 nivolumab-treated patients for aHCC at five referral hospitals in Korea. Only patients classified as Child-Pugh Class A were included. Organ-specific response criteria were adopted from RECIST 1.1, according to the indicated primary sites, including the liver, lungs, lymph nodes and other sites of metastasis. Results: Baseline characteristics of the Ipi/Nivo and Nivo groups were comparable. However, 65.2% of patients in the Ipi/Nivo group had prior ICI exposure, compared with only 4.3% in the Nivo group. The objective response rate (ORR) of Ipi/Nivo was 29.0%. The Ipi/Nivo combination therapy elicited OSORRs for 204 individual lesions: 18.0% in the liver, 17.7% in the lungs, 30.0% in the lymph nodes, and 12.5% in other sites. Within the Ipi/Nivo group, the ORR was 45.8% for patients without prior ICI exposure and 20.0% for those with prior ICI exposure. Patients without prior ICI exposure demonstrated OSORRs for 72 individual lesions: 29.0% in the liver, 31.3% in the lungs, 33.3% in the lymph nodes, and 23.1% at other sites. Conversely, patients with prior ICI exposure exhibited OSORRs for 132 individual lesions: 11.5% in the liver, 11.4% in the lungs, 27.8% in the lymph nodes, and 7.4% at other sites. Patients who exhibited a response in one organ were more likely to demonstrate responses in other organs irrespective of the organ type, with only two patients exhibiting variable responses across different organs. Furthermore, these responders had improved survival outcomes, including longer progression-free survival and overall survival, compared with non-responders. In terms of nivolumab monotherapy, the ORR was 21.3%. Nivo yielded OSORRs for 305 individual lesions: 13.5% in the liver, 25.3% in the lungs, 39.3% in the lymph nodes, and 18.4% at other sites. Conclusions: In contrast to lesions of patients who received Nivo, intrahepatic lesions of Ipi/Nivo-treated patients without prior ICI exposure exhibited favorable responses, comparable with treatment responses of extrahepatic lesions. Conversely, Ipi/Nivo-treated patients with prior ICI exposure had reduced organ-specific responses across all organs when compared with those without prior ICI exposure.

Dual-energy CT iodine concentration as a biomarker for immunotherapy treatment response in metastatic melanoma and renal cell carcinoma patients.

To investigate the predictive value of tumor iodine concentration obtained with dual-energy CT (DECT) for treatment response in patients treated with immune checkpoint inhibitors (ICI). Retrospective single-center study of consecutive metastatic melanoma and renal cell carcinoma (RCC) patients undergoing first-line ICI treatment. The iodine concentration measurement time points include prior to initiation of therapy (baseline [BL]), after initiation (follow-up [FU1]), and either time point nearest to 12 months or at time of progression (final follow-up [FFU]). Target lesion DECT-based whole-volume tumor normalized iodine concentration average (NICave) and size measurements were obtained. Reference standard was individual lesion FFU status categorized as responders or nonresponders per RECIST 1.1. Logistic regression model assessed NICave change and FU1 lesion response as predictors of FFU lesion outcome. Model's performance was summarized with AUC. Intraclass correlation coefficient (ICC) summarized inter-rater agreement of NICave. Forty-six patients were included (mean age 61 ± 11 years, 12 women; 16 melanoma). Sixty-four of 175 target lesions were confirmed nonresponders at FFU. In a multivariable model, lesion status at FU1 (odds ratio [OR]: 27.4, p < 0.001) and changes in NICave from BL to FU1 (OR: 2.42 per 1-SD increase, p = 0.019) were significant predictors of lesion status at FFU. The model's AUC was 0.86 (95% CI: 0.76-0.93). Inter-rater reliability of NICave was 0.98 (95% CI: 0.97-0.99). Changes in iodine concentration from baseline to first follow-up improve identification of delayed responding metastatic melanoma and RCC lesions treated with immune checkpoint inhibitor, initially classified as nonresponders by size change. Question How can pseudoprogression/delayed treatment response in metastatic renal cell carcinoma (RCC) and melanoma patients on first-line immune checkpoint inhibitors be accurately identified? Findings Combining iodine concentration change from Dual-energy CT (baseline to first follow-up) with RECIST-based lesion size change improved prediction of final lesion outcome. Clinical relevance DECT-based whole-volume tumor iodine concentration for target lesions is useful as a predictive imaging biomarker for distinguishing delayed response from true progression in patients with metastatic RCC and melanoma treated with first-line immune checkpoint inhibitors.

Effect of sugar beet variety resistance on the disease epidemiology of Cercospora beticola.

Cercospora leaf spot (CLS), caused by Cercospora beticola, is the most destructive foliar disease in sugar beet. CLS is conventionally controlled with fungicide, but the emergence of fungicide-resistant populations reinforces the importance of developing and cultivating resistant varieties. Understanding the dynamics of CLS in different varieties is hence essential for sustainable CLS management. Field experiments (2022 and 2023) with four sugar beet varieties possessing different resistant properties were conducted to describe the relationship between the variety resistance and the disease epidemiology of C. beticola. For this purpose, spore flight and disease progression were assessed on a weekly basis. Disease severity (DS) and disease incidence (DI) were delayed in resistant varieties compared to the susceptible and moderately susceptible ones. This finding was further confirmed by a model-based analysis of DS and DI for all varieties. Weekly spore flight monitoring during the vegetation period showed a similar tendency of reduced spore quantity by the resistant varieties. This was probably due to the lower DS, as no differences were found when the amount of fungal DNA was determined in individual lesions from the different varieties. Analysis of relative yield loss further confirmed the advantage of growing resistant varieties. Our results highlight that resistant varieties delay disease onset resulting in less severe symptoms and reduced spore flight. We also proved that aerial spore flight intensity could reflect the resistant property of each variety. These results provide a deeper insight into the interaction between variety resistance and CLS epidemiology, emphasizing variety-specific CLS management. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

AS3MT Gene Variant Shows Association with Skin Lesions in an Arsenic Exposed Population of India.

AS3MT, GSTO2, and GSTP1 genes play important roles in the arsenic biotransformation pathway, while CYP2E1 gene has a prominent role in the metabolic activation of xenobiotics. Hence, polymorphisms of these genes might have an effect on arsenic biotransformation and could impact susceptibility to arsenical skin lesions in individuals of chronic arsenic toxicity. The present case-control study, comprising 148 subjects, attempted to evaluate genetic association between nine polymorphisms of AS3MT, GSTO2, GSTP1 and CYP2E1 genes and arsenical skin lesions in a West Bengal (WB) population. A statistically significant association was found between rs11191439 (AS3MT) and arsenical skin lesions (OR = 5.50, P-value = 0.01) using logistic regression with age and gender as covariates. Among non-genetic risk factors, age and groundwater arsenic were found to be significantly associated with skin lesions (P-value < 0.05). When haplotypes among the intragenic polymorphisms of AS3MT, CYP2E1 and GSTO2 genes were analyzed, 'ATA' and 'ACG' haplotypes of the AS3MT gene showed significant difference between the case and control. Multifactor dimensionality reduction (MDR) analysis was performed on the nine polymorphisms and groundwater and urinary arsenic for studying gene-environment interactions. Strong association was observed between groundwater arsenic and skin lesions relative to the SNPs (P-value < 10-5). The best model with maximum testing accuracy included one SNP from the AS3MT (rs11191439) and groundwater arsenic (P-value < 0.0001). The present study documents the first report about the association of AS3MT gene variant with skin lesions in an arsenic exposed population of WB. Presumably, this is also the first study that has used MDR to investigate gene-environment interactions in arsenic-induced toxicity.

Dynamic Expansion and Contraction of Multiple Sclerosis T2-Weighted Hyperintense Lesions Are Present Below the Threshold of Visual Perception.

The study of T2-weighted hyperintense lesions resulting from autoimmune inflammatory injury and associated volumes within the CNS remains fundamental to the diagnosis and disease surveillance of MS. We investigated the dynamic changes of individual T2-weighted hyperintense MS lesions on MRI and hypothesized that variations may be present below the threshold of visual perception when evaluating longitudinal data. A retrospective study was performed of people with MS, incorporating data from 3 consecutive MRI time points acquired within a single academic center. All included MRI studies lacked formal imaging interpretations of newly enlarging or contracting T2-weighted hyperintensities. Well-defined, noncoalescing, individual T2-weighted hyperintense lesions were targeted. A total of 8-12 lesions were randomly selected in a blinded fashion at MRI time point 1 and 3D lesion volumes were followed over MRI time points 2 and 3. The impact of treatment on lesion expansion and relationship to brain MRI advancement, patient-reported progression of disease, and physician-identified progression was also studied. The study cohort comprised 115 people (81 (70.4%) women; mean disease duration of 9.36 years [standard deviation: 7.72 years]) who were primarily White (79.1%). A total of 1426 focal T2-weighted hyperintense MS lesions were identified on MRI time point 1 and longitudinally followed over MRI time points 2 and 3. In the evaluation of raw changes in individual T2-weighted hyperintense lesion volumes from MRI time point 1 to MRI time point 2, a similar number of individuals were observed with predominantly expanding (49/115; 42.6%) or contracting (51/115; 44.3%) lesions. However, most lesions expanded in volume (48/115; 41.7%) versus those that contracted (45/115; 39.1%) when evaluating MRI time point 3 to time point 1. Those individuals not on active treatment had a 67.15% reduction in the odds of more individual lesions predominantly contracting in volume relative to those on low-efficacy disease modifying therapy treatment (95% CI = [-83.89% to -33.01%], P = .0008) and 74.02% reduction relative to high-efficacy treatment individuals (95% CI = [-87.37% to -46.56%], P < .0001). Dynamic changes in T2-weighted hyperintense lesions are abundant, occurring below the threshold of visual perception and are present more frequently in untreated individuals.

Photodynamic Therapy Effects with Curcuma longa L. Active Ingredients in Gel and Blue LED on Acne: A Randomized, Controlled, and Double-Blind Clinical Study

Photodynamic therapy (PDT) using the photosensitizer curcumin and blue light has a relevant effect on bacteriological decontamination caused by C. acne. The aim is to verify PDT’s effectiveness with curcumin in individuals diagnosed with moderate to severe acne. This study was carried out on a total of 35 volunteers of both genders (12–32 years old), with moderate to severe acne vulgaris. The volunteers were randomized into five groups: L (LED), V (Vehicle), C (Curcumin), L + V (LED + Vehicle), and L + C (LED + Curcumin). The curcumin gel and LED with blue wavelength (450 nm ± 10 nm) were used. Qualitative and quantitative evaluations were used to verify the efficacy of the treatment by counting inflamed and non-inflamed lesions. The L + C group until day 30 showed a lower percentage of inflammatory lesions than the Vehicle group for the same period. On day 60, the L + C group showed lower inflammatory lesion values compared to the other groups. Intragroup analysis of hydration in the Vehicle group (V) showed a difference on days 30 and 60 compared to day zero. In an intragroup analysis, the L + C group showed a decrease in the mean scores on day 30, and day 60 compared to day zero, showing an improvement in the psychosocial status of these volunteers. Taken together, our results showed that the combination of blue LED therapy and curcumin proved to be an effective and safe treatment for reducing inflamed acne lesions in individuals with moderate to severe acne, while also enhancing their quality of life from a psychosocial perspective.

Prolonged persistence of mutagenic DNA lesions in somatic cells.

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment1-3. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours3,4, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium5-12. Persistent DNA lesions occurred at increased rates, with distinctive mutational signatures, in donors exposed to tobacco or chemotherapy, suggesting that they can arise from exogenous mutagens. In haematopoietic stem cells, persistent DNA lesions, probably from endogenous sources, generated the characteristic mutational signature SBS1913; occurred steadily throughout life, including in utero; and endured for 2.2 years on average, with 15-25% of lesions lasting at least 3 years. We estimate that on average, a haematopoietic stem cell has approximately eight such lesions at any moment in time, half of which will generate a mutation with each cell cycle. Overall, 16% of mutations in blood cells are attributable to SBS19, and similar proportions of driver mutations in blood cancers exhibit this signature. These data indicate the existence of a family of DNA lesions that arise from endogenous and exogenous mutagens, are present in low numbers per genome, persist for months to years, and can generate a substantial fraction of the mutation burden of somatic cells.

Lesion correlates of impaired acoustic-phonetic perception after unilateral left hemisphere stroke.

Acoustic-phonetic perception refers to the ability to perceive and discriminate between speech sounds. Acquired impairment of acoustic-phonetic perception is known historically as "pure word deafness" and typically follows bilateral lesions of the cortical auditory system. The extent to which this deficit occurs after unilateral left hemisphere damage and the critical left hemisphere areas involved are not well defined. We tested acoustic-phonetic perception in 73 individuals with chronic left hemisphere stroke and performed multivariate lesion-symptom mapping incorporating controls for non-specific task confounds, pure tone hearing loss, response bias, and lesion size. Separate analyses examined place of articulation, manner of articulation, voicing, and vowel discriminations. Overlap of the lesion map with transcallosal pathways linking left and right temporal lobes was examined using a probabilistic diffusion tensor tractography map of these pathways obtained from a healthy control cohort. Compared to an age- and education-matched control sample, 18% of the patients had impaired acoustic-phonetic perception overall, with 44% impaired on voicing, 26% on manner, 15% on place, and 14% on vowel discrimination. Lesion-symptom mapping revealed the most critical areas to be the transverse temporal gyrus (TTG) and adjacent medial belt cortex, the acoustic radiation, and the posterior superior temporal sulcus (pSTS). There were notable differences between lesion correlates for the different types of discrimination, with place discrimination linked to medial TTG, vowel discrimination to lateral TTG and planum temporale, manner discrimination to posterior planum temporale, and voicing discrimination to pSTS. Overlap of the main lesion map with transcallosal temporal lobe pathways was minor but included a deep white matter component at the base of the middle and inferior temporal gyri. The extent of overlap between individual lesions and the transcallosal pathway map was not correlated with acoustic-phonetic perception. The results add further evidence that acoustic-phonetic impairments, particularly impairments of voicing perception, are relatively common after unilateral left temporal lobe damage, and they clarify the lesion correlates of these deficits. Differences between the lesion maps for the discrimination types likely reflect differential reliance on spectral versus temporal analysis for these discriminations.

Discussion on the Splitting Treatment Technique in Gamma Knife Treatment Plans

Objective: In clinical Gamma Knife treatment, when patients have multiple or large lesions, a single Gamma Knife plan may require extended treatment time, making it difficult for patients to complete the session. This study explores the proper application of the splitting treatment technique in Gamma Knife treatment plans to create segmented plans for patients. Methods: Utilizing the design and output functions of the radiotherapy planning system, this study examines the typical errors in clinical treatment plans designed for the Moonlight Gamma Knife. Different splitting approaches were analyzed by comparing beam-on time for each target and calculating beam-on time error rates. Based on this, the appropriate splitting treatment technique for Gamma Knife treatment plans was discussed. Results: Scenarios where dose curves of multiple lesions intersect were categorized into three types: complete intersection, partial intersection, and no intersection. Complete intersection cases were further divided into Type I and Type II complete intersections. For cases with completely intersecting dose curves, the Gamma Knife plans should be split using the upper-lower segmentation method. For cases with no intersection, plans can be split based on individual lesions. For partial intersection cases, either the upper-lower segmentation or lesion-based segmentation method may be used. However, careful handling of target weighting at the dose curve intersection is necessary to ensure dose accuracy. For large lesions, the upper-lower segmentation method is recommended. Conclusion: To meet clinical treatment requirements, the proper application of the splitting treatment technique in Gamma Knife treatment plans is essential. This ensures dose accuracy in radiotherapy, thereby guaranteeing treatment efficacy and patient safety.

Late-onset, giant juvenile xanthogranuloma

Juvenile xanthogranuloma (JXG) is the most prevalent form of non-Langerhans cell histiocytosis. The typical presentation includes small papules or nodules in infants, often resolving spontaneously within a few years without treatment. Histologically, it showcases lipid-laden macrophages and Touton giant cells. However, atypical cases may manifest as larger lesions in older individuals, lacking foamy histiocytes and displaying increased mitotic activity. It is important to consider JXG as a potential diagnosis for skin lesions before assuming malignancy. Immunohistochemistry markers such as CD163, CD4, and CD31 can be instrumental in confirming the diagnosis. In this report, reviewing the literature, we present one such unique case of JXG.

Assessment of the relationship between functional dependency and cognitive status with skin lesions in elderly individuals

Introduction: Skin lesions observed concomitantly with increasing functional dependency and/or cognitive impairment can lead to significant additional challenges. In this study, we aimed to assess the relationship between functional dependency, cognitive status, and skin lesions in elderly individuals Methods: Individuals presenting to the geriatric outpatient clinic of a tertiary reference center were included in a cross-sectional study. The level of dependency was determined using the Katz Index of Independence in Activities of Daily Living (ADL) and the Lawton-Brody Instrumental Activities of Daily Living (IADL) scale, classifying individuals as "totally dependent," "partially dependent," or "independent." Cognitive status was assessed using the Standardized Mini-Mental State Examination (MMSE), with scores of 24 and above considered "normal." Results: Of the 228 individuals included in the study, 63.60% were male, with a mean age of 76.20 (±7.10) years. The three most commonly observed skin findings in the study group were scar (43.90%), xerosis (40.40%), and dermatophytosis (36.40%). It was revealed that the occurrence of xerosis, infection-related lesions, eczema, diabetic foot ulcers, decubitus ulcers, and pruritus was statistically significantly lower in individuals with "totally independent" ADL, "totally independent" IADL, and/or "normal" cognitive function assessed by MMSE. Conclusion: There is a significant relationship between functional and cognitive status and the occurrence of skin lesions in elderly individuals. Certain skin lesions such as xerosis, infection-related lesions, eczema, diabetic foot ulcers, decubitus ulcers, and pruritus may be particularly common in elderly individuals who are functionally dependent and/or have impaired cognitive functions and should be taken into consideration in clinical practice.

Abstract C180: Not all PIRADS 3s are equal; fusion biopsy outcomes by PIRADS score and ethnicity in a diverse population

Abstract Introduction and Objective: Magnetic resonance imaging (MRI) is increasingly utilized in the diagnosis of prostate cancer (PCa). Although PIRADS 3 lesions have been associated with a lower likelihood of detecting clinically significant prostate cancer (csPCa) at the time of targeted fusion biopsy (FB), existing data on multiethnic populations are sparse. We assessed the pathologic concordance of PIRADS 3 vs 4 or 5 lesions in detection of PCa and csPCa in comparison to PSA density in a diverse population. Methods: A retrospective study of all patients who underwent image-guided FB for PIRADS 3-5 lesions from 2016-2022 was conducted. Demographic, clinical, and pathologic data were extracted from electronic medical records. Mixed-effects logistic regression models were used to examine the association of race/ethnicity and PSA density with risks of overall PCa and csPCa. A stratified analysis by PIRADS score (3 vs 4 or 5) was also carried out to explore the associations between detection rates of PCa and race/ethnicity. Results: A total of 565 men with 997 lesions were analyzed, with average age 63.2 years (SD: 7.5) at the time of biopsy. Of the men, 279 (49.4%) were Non-Hispanic Black (NHB), 112 (19.8%) were Non-Hispanic White, and 174 (30.8%) were Hispanic. 520 (52.16%), 310 (31.09%), and 167 (16.75%) individual MRI lesions were PIRADS 3, 4, and 5, respectively with distributions of PIRADS scores being similar across all race/ethnicities. The overall rates of PCa detection were 44.8% in NHB, 37.6% in Hispanics, and 33.0% in NHW. Compared to NHW, NHB has 2.52 higher odds of detecting overall PCa (95% CI 1.10-5.78; p = 0.03), whereas Hispanic men had an OR = 1.18 (p = 0.72). Interestingly, the increase in PCa detection among NHB was only observed for PIRADs 3 lesions (OR = 4.84 95% CI 1.11-21.2, p = 0.04). NHB men also had 2.1-fold higher odds of detecting csPCa (95% CI 0.92-4.77; p = 0.08) in comparison to NHW with a similar trend mimicking association with PRIADS scores, although results were not statistically significant. Conclusions: We report that NHB men have higher odds of detection rates of overall PCa in FB in comparison to NHW and Hispanic men, albeit only at PIRADS 3 scores. These findings may serve to improve risk stratification and assist with shared decision making when discussing triggers for biopsy. Source of funding: None Citation Format: David G. Hanelin, Andrewe Baca, Priya Dave, Rutul Patel, Ilir Agalliu, Alexander Sankin, Ahmed Aboumohamed, Kara Watts. Not all PIRADS 3s are equal; fusion biopsy outcomes by PIRADS score and ethnicity in a diverse population [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C180.

Objective Determination of Site-of-Lesion in Auditory Neuropathy.

Auditory neuropathy (AN), a complex hearing disorder, presents challenges in diagnosis and management due to limitations of current diagnostic assessment. This study aims to determine whether diffusion-weighted magnetic resonance imaging (MRI) can be used to identify the site and severity of lesions in individuals with AN. This case-control study included 10 individuals with AN of different etiologies, 7 individuals with neurofibromatosis type 1 (NF1), 5 individuals with cochlear hearing loss, and 37 control participants. Participants were recruited through the University of Melbourne's Neuroaudiology Clinic and the Murdoch Children's Research Institute specialist outpatient clinics. Diffusion-weighted MRI data were collected for all participants and the auditory pathways were evaluated using the fixel-based analysis metric of apparent fiber density. Data on each participant's auditory function were also collected including hearing thresholds, otoacoustic emissions, auditory evoked potentials, and speech-in-noise perceptual ability. Analysis of diffusion-weighted MRI showed abnormal white matter fiber density in distinct locations within the auditory system depending on etiology. Compared with controls, individuals with AN due to perinatal oxygen deprivation showed no white matter abnormalities ( p > 0.05), those with a neurodegenerative conditions known/predicted to cause VIII cranial nerve axonopathy showed significantly lower white matter fiber density in the vestibulocochlear nerve ( p < 0.001), while participants with NF1 showed lower white matter fiber density in the auditory brainstem tracts ( p = 0.003). In addition, auditory behavioral measures of speech perception in noise and gap detection were correlated with fiber density results of the VIII nerve. Diffusion-weighted MRI reveals different patterns of anatomical abnormality within the auditory system depending on etiology. This technique has the potential to guide management recommendations for individuals with peripheral and central auditory pathway abnormality.

Effect of Online Training on the Reliability of Assessing Sacroiliac Joint Radiographs in Axial Spondyloarthritis: A Randomized, Controlled Study.

Radiographic assessment of sacroiliac joints (SIJs) according to the modified New York (mNY) criteria is key in the classification of axial spondyloarthritis but has moderate interreader agreement. We aimed to investigate the improvements of the reliability in scoring SIJ radiographs after applying an online real-time iterative calibration (RETIC) module, in addition to a slideshow and video alone. Nineteen readers, randomized to 2 groups (A or B), completed 3 calibration steps: (1) review of manuscripts, (2) review of slideshow and video with group A completing RETIC, and (3) re-review of slideshow and video with group B completing RETIC. The RETIC module gave instant feedback on readers' gradings and continued until predefined reliability ([Formula: see text]) targets for mNY positivity/negativity were met. Each step was followed by scoring different batches of 25 radiographs (exercises I to III). Agreement ([Formula: see text]) with an expert radiologist was assessed for mNY positivity/negativity and individual lesions. Improvements by training strategies were tested by linear mixed models. In exercises I, II, and III, mNY [Formula: see text] were 0.61, 0.76, and 0.84, respectively, in group A; and 0.70, 0.68, and 0.86, respectively, in group B (ie, increasing, mainly after RETIC completion). Improvements were observed for grading both mNY positivity/negativity and individual pathologies, both in experienced and, particularly, inexperienced readers. Completion of the RETIC module in addition to the slideshow and video caused a significant [Formula: see text] increase of 0.17 (95% CI 0.07-0.27; P = 0.002) for mNY-positive and mNY-negative grading, whereas completion of the slideshow and video alone did not ([Formula: see text] = 0.00, 95% CI -0.10 to 0.10; P = 0.99). Agreement on scoring radiographs according to the mNY criteria significantly improved when adding an online RETIC module, but not by slideshow and video alone.

68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging-A First-in-Human Case Series.

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [68Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [68Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68Ga from a 68Ge/68Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [68Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7-95.3), and the mean SUVmean was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [68Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

Treatment of tandem occlusions of the common and internal carotid arteries

Proximal carotid tandem lesions are defined as multilevel lesions with significant (> 50%) atherosclerotic disease involving the internal carotid artery (ICA) in combination with the proximal ipsilateral common carotid artery (CCA) or innominate artery (IA). It is arelatively rare disease with an incidence of less than 5% in all patients with carotid stenosis at the level of the bifurcation. These patients are at high surgical risk and were, therefore, excluded from current randomized controlled trials. Although the effectiveness of carotid endarterectomy (CEA) and carotid stenting (CAS) in stroke prevention for patients is established, the optimal treatment approach for the subgroup of patients with aproximal tandem lesion is still controversial. Treatment of this condition is not well understood because it is difficult to determine the risk of each individual lesion becoming symptomatic. Therefore, concurrent treatment of severe (> 70% stenosis) proximal lesions is recommended when treating severe stenosis at the carotid bifurcation. This disease can lead to embolic ischemic strokes or hemodynamic compromise. It is not possible to determine diagnostically which lesion led to the clinical symptoms, which is why both lesions should be corrected.

Measuring repeatability of dynamic contrast-enhanced MRI biomarkers improves evaluation of biological response to radiotherapy in lung cancer.

To measure dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarker repeatability in patients with non-small cell lung cancer (NSCLC). To use these statistics to identify which individual target lesions show early biological response. A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (Ktrans), extravascular extracellular space volume fraction (ve) and plasma volume fraction (vp) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation. Fourteen patients (mean age, 67 years +/- 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for vp, which was 42.44%. Cohort-level changes were significant for Ktrans and ve (p < 0.001) and tumour volume (p = 0.002). Ktrans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in ve despite the cohort-level change. Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies. Dynamic contrast-enhanced magnetic resonance imaging biomarkers Ktrans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics. Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility. Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable. Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment.

Oxygen-Enhanced MRI Detects Incidence, Onset, and Heterogeneity of Radiation-Induced Hypoxia Modification in HPV-Associated Oropharyngeal Cancer.

Hypoxia mediates treatment resistance in solid tumors. We evaluated if oxygen-enhanced MRI-derived hypoxic volume (HVMRI) is repeatable and can detect radiotherapy-induced hypoxia modification in human papillomavirus-associated oropharyngeal head and neck squamous cell cancer. A total of 27 patients were recruited prospectively between March 2021 and January 2024. HVMRI was measured in primary and nodal tumors prior to standard-of-care (chemo)radiotherapy and then at weeks 2 and 4 (W2 and W4) into therapy. Two pretreatment scans assessed biomarker within-subject coefficient of variation and repeatability coefficient (RC). Cohort treatment response was measured using mixed-effects modeling. Responding lesions were identified by comparing HVMRI change with RC limits of agreement. Oxygen-enhanced MRI identified hypoxia in all lesions. The HVMRI within-subject coefficient of variation was 24.6%, and RC limits of agreement were -45.7% to 84.1%. A cohort median pretreatment HVMRI of 11.3 cm3 reduced to 6.9 cm3 at W2 and 5.9 cm3 at W4 (both P < 0.001). HVMRI was reduced in 54.5% of individual lesions by W2 and in 88.2% by W4. All lesions with W2 hypoxia reduction showed persistent modification at W4. HVMRI reduced in some lesions that showed no overall volume change. Hypoxia modification was discordant between primary and nodal tumors in 50.0% of patients. Radiation-induced hypoxia modification can occur as early as W2, but onset varies between patients and was not necessarily associated with overall size change. Half of all patients had discordant changes in primary and nodal tumors. These findings have implications for patient selection and timing of dose de-escalation strategies in human papillomavirus-associated oropharyngeal carcinoma. See related commentary by Mason, p. 5503.

Spectral-domain OCT characteristics of intraretinal hyper-reflective foci associated with age-related macular degeneration and diabetic retinopathy

ObjectiveThe purpose of this study was to quantitatively analyze and compare OCT characteristics of intraretinal hyper-reflective foci (IHRF) in eyes with diabetic retinopathy (DR) versus age-related macular degeneration (AMD). Designa retrospective observational study. Participants54 treatment-naïve eyes (27 DR and 27 AMD). MethodsThe IHRF lesions in OCT B-scan were semi-automatically segmented. Mean reflectivity (MR), maximum diameter, circularity index (Cir), area, and the angle between the greatest linear dimension (GLD) and the horizontal were computed for each IHRF lesion. The presence and absence of a posterior shadow and the axial location were assessed. The MR was normalized using the vitreous and nerve fiber layer reflectance as dark and bright reference standards, respectively. ResultsA total of 1149 IHRF (1051 in DR and 98 in the AMD group) were identified, with a mean of 39 ± 36 lesions in DR eyes compared to only 4 ± 4 in AMD eyes (p < 0.001). The mean area of individual IHRF lesions was greater in DR eyes (1305 ± 1647 μm² vs 1031 ± 750 μm²; p = 0.016), but IHRF in AMD eyes had higher reflectivity (1.17 ± 0.14 vs 1.03 ± 0.17; p < 0.001). The angle of the GLD relative to the horizontal was greater in AMD eyes, indicating that IHRF in AMD eyes were more horizontally oriented. In AMD eyes, 88.8% of IHRF were located beneath the inner border of the outer nuclear layer (ONL), while in DR eyes, 56.9% were located there (p < 0.001). ConclusionsIHRF lesions in eyes with DR and AMD demonstrate significant differences, with IHRF in DR eyes tending to be larger and less hyper-reflective compared to AMD eyes.

Oral Granulomatous Disorders: A Diagnostic Insight.

Granulomatous inflammation represents a unique pattern of chronic inflammation observed in a restricted form of infectious and certain non-infectious diseases. The formation of granulomas typically involves immune responses. Granulomatous disorders encompass a broad spectrum of conditions that share the common histological feature of granuloma formation. Their involvement in the oral soft and hard tissues is quite infrequent; however, their manifestation can pose a diagnostic challenge due to the diverse range of potential causes and the relatively non-specific appearance of the individual lesions. The ultimate outcome of a complex entails the formation of a granuloma, resulting from the interplay among an invading pathogen or antigen, chemical substance, medication, or other irritant, persistent presence of antigens in the bloodstream, activation of macrophages, initiation of Th1 cell response, B-cell overactivity, presence of circulating immune complexes, and a wide range of biological signaling molecules, ultimately leading to the development of fibrosis attributed to the actions of transforming and platelet-derived growth factor. This article emphasizes the clinicopathological diagnostic criteria of oral granulomatous disorders as a guide for treatment and management.