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Imaging tumor microenvironment: clinical experience with 68Ga-FAPI PET/CT across multiple cancer types

Q J Nucl Med Mol Imaging. 2026 Mar 19. doi: 10.23736/S1824-4785.26.03673-3. Online ahead of print.

ABSTRACT

BACKGROUND: Fibroblast activation protein (FAP) is highly expressed in the stroma of various cancers, making it a promising target for positron emission tomography (PET) imaging. This study aimed to evaluate the clinical performance of 68Ga-labeled fibroblast activation protein inhibitor (FAPI)-46 PET/CT across multiple cancer types.

METHODS: In this single-center, retrospective study, we included 22 patients (mean age 43 years, range 10-69) with histopathologically confirmed primary or metastatic cancers in whom 18F-FDG PET/CT or conventional imaging yielded inconclusive results. All patients underwent 68Ga-FAPI-46 PET/CT. Scan positivity was determined by two experienced nuclear medicine physicians based on non-physiologic tracer uptake. Malignancy was confirmed by histopathology (the reference standard) or correlative imaging follow-up. Analysis was performed on both a per-patient and per-lesion basis. Tumor uptake was quantified using maximum standardized uptake value (SUV<inf>max</inf>) and tumor-to-background ratio (TBR). Statistical comparisons of SUV<inf>max</inf> and TBR between different groups were performed using Student’s t-tests.

RESULTS: A total of 115 lesions were identified and evaluated across 12 different cancer types. The highest 68Ga-FAPI-46 avidity (SUV<inf>max</inf>>12) was observed in sarcoma, breast cancer, and cholangiocarcinoma, while the lowest uptake (SUV<inf>max</inf><6) was found in renal cell, differentiated thyroid, and gastric cancers. Intermediate uptake (SUV<inf>max</inf> 6-12) was seen in hepatocellular, colorectal, and ovarian cancers. Due to minimal background activity (muscle and blood pool SUV<inf>max</inf><2), TBRs were high, exceeding 3-fold for intermediate and 6-fold for high-uptake tumors.

CONCLUSIONS: 68Ga-FAPI-46 PET/CT provides high-contrast imaging across a wide spectrum of malignancies, demonstrating particularly strong potential for visualizing tumors with prominent stromal components. These findings suggest a significant clinical role for this modality in improving tumor staging, restaging, and therapy assessment, especially in cases where 18F-FDG PET/CT is suboptimal.

PMID:41854637 | DOI:10.23736/S1824-4785.26.03673-3

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Surgical treatment of epilepsy in polymicrogyria: A subject-level meta-analysis and decision-making framework

Epilepsia. 2026 Mar 19. doi: 10.1002/epi.70204. Online ahead of print.

ABSTRACT

OBJECTIVE: Polymicrogyria (PMG) presents a complex challenge in epilepsy surgery. The optimal surgical strategy and extent of resection, from hemispheric to more limited approaches, remain debated. We aimed to summarize subject-level surgical outcomes and identify factors informing procedure selection.

METHODS: We conducted a subject-level pooled analysis of 161 patients across 20 retrospective studies, evaluating surgical outcomes (Engel classification), in relation to anatomic extent, surgical procedure, use of intracranial electroencephalography (ICEEG), and other decision-influencing factors.

RESULTS: At ≥12 months follow-up, ~70% of patients achieved seizure freedom (Engel Class I). In our univariate analysis Engel Class I outcomes were associated with shorter epilepsy duration (8.05 vs 11.92 years, p = 0.009). Hemispheric PMG was linked to earlier seizure onset (p = 0.02) and a higher incidence of epileptic encephalopathy with spike-wave activation in sleep (p < 0.0005). Among unilateral non-hemispheric and bilateral PMG cases, seizure-freedom rates were similar between hemispheric and more limited resections, but the latter were associated with a lower incidence of new or worsened motor deficits. Mixed-effects logistic regression (n = 160) showed that hemispheric surgery increased the odds of seizure freedom but without statistical significance (odds ratio [OR] = 3.52, p = 0.055). ICEEG did not significantly influence seizure outcomes but may play a key role in identifying eloquent cortex and guiding safer, tailored resections.

SIGNIFICANCE: In PMG-related epilepsy, surgical strategy must balance seizure control with preservation of function. ICEEG (especially stereo-EEG [SEEG]) remains a valuable tool for functional mapping and tailored resections.

PMID:41854623 | DOI:10.1002/epi.70204

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Early Warning Scores in Emergency Department Patients Aged 80 Years or Older

JAMA Netw Open. 2026 Mar 2;9(3):e261532. doi: 10.1001/jamanetworkopen.2026.1532.

ABSTRACT

IMPORTANCE: Early warning scores (EWSs) are widely used tools to support triage and risk stratification in the emergency department (ED). However, data on their performance in identifying clinical deterioration among acutely ill adults aged 80 years or older are scarce.

OBJECTIVE: To evaluate and compare the performance of 5 EWSs for predicting short-term clinical deterioration in ED patients aged 80 years or older.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective prognostic study included all consecutive nontrauma ED visits by patients aged 80 years or older between January 2015 and December 2024 at a large urban teaching hospital in Rome, Italy.

EXPOSURES: Physiologic parameters recorded at ED admission were used to calculate 5 EWSs: National Early Warning Score (NEWS), National Early Warning Score 2 (NEWS2), Modified Early Warning Score (MEWS), Rapid Emergency Medicine Score (REMS), and International Early Warning Score (IEWS).

MAIN OUTCOMES AND MEASURES: The primary outcome was clinical deterioration, defined as death or intensive care unit (ICU) admission within 24 hours of ED arrival. Discrimination was assessed by area under the receiver operating characteristic curve (AUROC), calibration by the Brier score, and age-related performance by spline regression. Comparative contributions of variables were analyzed using Shapley additive explanations (SHAP) values.

RESULTS: Among 50 645 patients (median age, 85 years [IQR, 82-88 years]; 54.6% females), 1233 (2.4%) experienced clinical deterioration. All EWSs demonstrated fair discrimination (AUROC range, 0.747 [IQR, 0.731-0.763] for MEWS to 0.782 [IQR, 0.767-0.798] for NEWS). Whereas NEWS achieved the highest AUROC, REMS had the best calibration (Brier score, 0.0220; 95% CI, 0.0208-0.0232). Discriminatory performance declined with increasing age beyond 90 years except for REMS, whose predictive accuracy improved among patients older than 94 years. For patients aged 87 years or older vs 80 to 86 years, oxygen supplementation (SHAP difference, 0.59), systolic blood pressure (SHAP difference, 0.32), and Glasgow Coma Scale score (SHAP difference, 0.40) were the strongest predictors of clinical deterioration.

CONCLUSIONS AND RELEVANCE: In this prognostic study of EWSs conducted among ED patients aged 80 years or older, all scores provided acceptable short-term prognostic accuracy. REMS demonstrated the most consistent performance in patients aged 94 years or older, supporting its use for targeted risk stratification in this population.

PMID:41854615 | DOI:10.1001/jamanetworkopen.2026.1532

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Colorectal Cancer Risk With Negative Colonoscopy or Nonadherence After Positive FOBT Screening

JAMA Netw Open. 2026 Mar 2;9(3):e262404. doi: 10.1001/jamanetworkopen.2026.2404.

ABSTRACT

IMPORTANCE: Population-based colorectal cancer (CRC) screening programs are implemented globally. When determining screening intervals, variations in the risk of subsequent CRC by colonoscopy outcome should be considered.

OBJECTIVE: To evaluate the incidence of CRC after a negative screening colonoscopy result or nonadherence to colonoscopy in individuals with a positive fecal occult blood test (FOBT) result.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted between January 1, 2008, and December 31, 2021. It was conducted within a population-based CRC screening program in the Stockholm-Gotland region, Sweden, using biennial FOBT as the primary screening test in the target population aged 60 to 69 years. The study cohort included all men and women born between 1938 and 1954 residing in the Stockholm-Gotland region between 2008 and 2012 who were invited to a CRC screening. All participants with a positive FOBT result were identified. Data provided by national registers were analyzed from October 2024 through January 2026.

EXPOSURES: Individuals with a positive FOBT result were categorized as (1) having a negative result on recommended follow-up colonoscopy or (2) nonadherence to recommended follow-up colonoscopy.

MAIN OUTCOMES AND MEASURES: The primary outcome was CRC incidence compared with the general population (defined as all individuals in the cohort who were invited to screening, excluding those with negative colonoscopy or nonadherence following positive FOBT). This was measured by standardized incidence ratio (SIR).

RESULTS: Of 318 096 individuals invited to CRC screening with FOBT, 14 873 had a positive FOBT result (7799 male [52.4%]; median [IQR] age, 65 [63-67] years). Of these individuals, 11 473 (87.3%) underwent a colonoscopy, and 8433 of those colonoscopies (73.5%) were negative. Individuals with a negative screening colonoscopy result had a significantly lower observed CRC incidence (SIR, 0.52; 95% CI, 0.39-0.68) relative to the general population, with a lower SIR in men (0.37; 95% CI, 0.25-0.56) than women (0.71; 95% CI, 0.49-1.03). In contrast, individuals with a positive FOBT who did not adhere to follow-up colonoscopy had a markedly increased CRC incidence (SIR, 4.21; 95% CI, 3.24-5.48) compared with the general population.

CONCLUSIONS AND RELEVANCE: In this study, a decrease in CRC incidence was observed among individuals with negative results in screening colonoscopies, with a greater decrease in men, supporting risk-based, individualized follow-up strategies. A high-risk group for CRC was identified among individuals who did not adhere to follow-up colonoscopy, enabling targeted interventions to improve early CRC detection.

PMID:41854612 | DOI:10.1001/jamanetworkopen.2026.2404

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Digital twins and virtual cohorts: How is synthetic data used for real-world evidence?

Epidemiol Prev. 2026 Jan-Feb;50(1):94-99. doi: 10.19191/EP26.1.A902.022.

ABSTRACT

Synthetic data are artificially generated information with the aim of imitating real data. They are designed to preserve the statistical characteristics of the original population while ensuring high levels of privacy, which makes them particularly useful in contexts where confidentiality is crucial. Measuring the value of synthetic data means assessing the similarity with the original data, the ability to produce results comparable to those obtained with real data, and the potential risks of privacy breaches. However, some risks remain, including the possible re-identification of individuals, the danger of amplification of biases already present in the original data, and the difficulty in validating the quality of synthetically generated data. At present, synthetic data represent an emerging and promising technology in various fields, however their use in epidemiology, particularly in observational settings, is still debated and requires further investigation and evaluation.

PMID:41854006 | DOI:10.19191/EP26.1.A902.022

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Activity-Informed Network Analysis Reveals Keystone Microbes Shaping Freshwater Ecosystem Function

Environ Microbiol Rep. 2026 Apr;18(2):e70245. doi: 10.1111/1758-2229.70245.

ABSTRACT

Freshwater lakes are dynamic ecosystems, with varying oxygen dynamics that influence microbiome structure, composition, and transcriptomic activity. In many freshwater studies, ecological function and abundance metrics are used to discover keystone species; however, it is well established that abundance does not equal activity. Despite the existence of long-term time series spanning multiple years, no previous study has looked at how microbial community and activity (metatranscriptomics) are influenced by shifting oxygen conditions across depths at the microbial network level. In this study, we leverage metagenome-assembled genomes and transcriptomic activity to identify keystone taxa in the ecosystem. Using the SPIEC-EASI and CARlasso methods, we mapped key microbial associations and used permutation-based analyses to assess the robustness of keystone identification. Our results reveal that a taxon’s ecological centrality is context-dependent and that many species identified as keystone by abundance alone do not exhibit corresponding transcriptional activity. Notably, members of Bacteroidota and other lineages emerged as keystone taxa only when both abundance and activity were considered. Our study underscores the importance of combining metagenomic and metatranscriptomic approaches for accurate identification of functionally relevant keystone species in freshwater ecosystems, providing a framework for future microbial ecology studies.

PMID:41853994 | DOI:10.1111/1758-2229.70245

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A preliminary validation of the traumatic grief inventory-kids-caregiver-report (TGI-K-CR)

Eur J Psychotraumatol. 2026 Dec;17(1):2638015. doi: 10.1080/20008066.2026.2638015. Epub 2026 Mar 19.

ABSTRACT

BACKGROUND: Prolonged grief disorder (PGD) is included in the Diagnostic and Statistical Manual of Mental Disorders text-revised fifth edition (DSM-5-TR) and in the International Classification of Diseases Eleventh Edition (ICD-11). While PGD screening instruments exist for adults, these instruments are not applicable to children. Caretakers play a crucial role in screening for PGD in children.

OBJECTIVE: We evaluated the psychometric properties of the Traumatic Grief Inventory-Kids-Caregiver-Report (TGI-K-CR) to screen for DSM-5-TR and ICD-11 PGD in children.

METHOD: On a website with information about grief, 196 Dutch caregivers (82% woman; Mage = 44) completed questions about their own and their child’s (47% girls; Mage = 11; 44% lost a parent) background and loss-related characteristics (77% of deaths resulted from illness). Caregivers completed the TGI-K-CR and a self-report measure about their own PGD intensity. Factor structure and internal consistency of DSM-5-TR and ICD-11 PGD items were examined separately. T-tests and correlation analyses examined whether caregiver-ratings of PGD intensity in children differed as a function of background- and loss-related characteristics. Provisional cut-offs for both criteria sets were determined.

RESULTS: Confirmatory factor analyses showed support for two distinct, but related, factors for DSM-5-TR and ICD-11 PGD items. We found strong internal consistency (ω = .85 for DSM-5-TR; ω = .87 for ICD-11), while some factor loadings were poor. In support of known-groups validity, DSM-5-TR and ICD-11 PGD intensity were higher in children when caregivers reported higher PGD intensity for themselves and when deaths occurred more recently. ROC analyses showed optimal cut-off scores of ≥46 and ≥52 to determine probable caseness for DSM-5-TR and ICD-11 PGD, respectively, when summing all 16 items.

CONCLUSIONS: The psychometric properties of the TGI-K-CR seem promising, but more research among larger samples is needed. This caregiver screening tool for PGD in children (aged 8-18) may advance child bereavement research and care.

PMID:41853993 | DOI:10.1080/20008066.2026.2638015

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Self-reported versus clinician-evaluated symptom assessment and diagnosis of ICD-11 PTSD and CPTSD: a comparison between the International Trauma Interview and the International Trauma Questionnaire

Eur J Psychotraumatol. 2026 Dec;17(1):2635917. doi: 10.1080/20008066.2026.2635917. Epub 2026 Mar 19.

ABSTRACT

Background: The ICD-11 introduced distinct criteria for Posttraumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD), necessitating validated assessment tools. While the International Trauma Questionnaire (ITQ) is a widely used self-report measure, the International Trauma Interview (ITI) is a structured clinician-administered interview considered a gold standard. This study investigated the correspondence between ITQ and ITI symptom and diagnostic classifications in a treatment-seeking veteran population.Methods: A sample of 108 Danish veterans completed both the ITQ and ITI. We calculated descriptive statistics, bivariate correlations, and Cohen’s κ values to assess agreement for individual symptom items and diagnostic categories (ICD-11 PTSD, CPTSD, and PTSD or CPTSD combined), using the ITI as the reference standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also determined.Results: ITQ scores were consistently higher than ITI scores across all symptom domains. Total symptom scores for PTSD, DSO, and CPTSD showed strong associations between instruments (r = .74 to .82, all p < .001). Agreement for individual symptom items varied from fair to substantial (κ = .33 to .70). The combined diagnosis of PTSD or CPTSD showed moderate agreement (κ = .60) with high sensitivity (0.94) and PPV (0.90). However, agreement for ICD-11 PTSD alone was fair (κ = .38), with low PPV (0.39) despite good sensitivity (0.65).Conclusion: The ITQ consistently reported higher symptom endorsement than the ITI. While the ITQ shows strong convergent validity for overall symptom burden and high sensitivity for screening trauma-related psychopathology (PTSD or CPTSD combined), its limited agreement for standalone ICD-11 PTSD diagnosis suggests it should not be used as a sole diagnostic tool. Comprehensive clinical interviews remain crucial for definitive diagnosis, while the ITQ can serve as an effective screening instrument.

PMID:41853968 | DOI:10.1080/20008066.2026.2635917

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Genomic insights into the tmexCD-toprJ: plasmid-mediated evolution, dissemination and diversity in bacterial populations

J Antimicrob Chemother. 2026 Mar 4;81(4):dkag107. doi: 10.1093/jac/dkag107.

ABSTRACT

BACKGROUND: The plasmid-mediated tigecycline resistance gene tmexCD-toprJ has emerged in clinical and animal isolates, but its epidemiological spread and plasmid adaptation mechanisms remain unclear.

METHODS: We characterized tmexCD-toprJ-carrying plasmids from the PLSDB database through comprehensive bioinformatic analyses, revealing their genetic features and potential inter-species transmission routes.

RESULTS: Genomic analysis of 197 tmexCD-toprJ-carrying plasmids revealed significant backbone diversity, clustering into 18 groups and 12 singletons. The 30 identified host species were predominantly Klebsiella pneumoniae (K. pneumoniae) (53.3%), followed by Pseudomonas aeruginosa (P. aeruginosa) (16.8%) and Klebsiella quasipneumoniae (K. quasipneumoniae) (4.1%). MOB-suite typing classified 53.8% as conjugative, 5.6% mobilizable and 40.61% non-mobilizable. Over half of the tmexCD-toprJ-carrying plasmids were predicted to contain the MOBH family. Among the identified variants, tmexCD1-toprJ1, tmexCD2-toprJ2 and tmexCD3-toprJ1 representing the predominant forms. TmexCD1-toprJ1 was linked to IncFIB/IncHI1B/rep_cluster_1254 plasmids, while tmexCD2-toprJ2 associated with diverse replicons, enabling cross-species spread. A total of 14 plasmids co-localized tmexCD-toprJ with carbapenemase (blaNDM/KPC) and mcr genes, forming high-risk resistance platforms. Notably, a 36 483 bp insertion in IncP/rep_cluster_1115 plasmids disrupted tmexC6D6-toprJ1b and carried heavy metal resistance genes.

CONCLUSIONS: These findings enhance our understanding of the diversity of tmexCD-toprJ-carrying plasmids. The convergence of tmexCD-toprJ with carbapenemase and polymyxin resistance genes in clinically prevalent plasmids underscores an urgent need for enhanced surveillance targeting complete genetic environments.

PMID:41853961 | DOI:10.1093/jac/dkag107

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Diagnostic Delay in Desquamative Gingivitis: An Observational Cohort Study

Oral Dis. 2026 Mar 19. doi: 10.1111/odi.70276. Online ahead of print.

ABSTRACT

OBJECTIVES: Non-plaque-induced gingivitis encompasses a heterogeneous group of conditions as defined in the 2017 Classification of Periodontal and Peri-Implant Diseases and Conditions. Recognition is challenging and often leads to diagnostic delay. This study aimed to evaluate diagnostic delay in a cohort of patients with non-plaque-induced gingivitis presenting as desquamative gingivitis, and to identify associated factors.

MATERIALS AND METHODS: In this observational study, patients were recruited from public and private oral medicine centres. Participants completed a questionnaire collecting demographic, social, and clinical information related to their condition. Association between variables and diagnostic delay were analyzed using the Student’s t-test (significance p < 0.05).

RESULTS: Eighty-six patients (43 from private and 43 from public centres) were enrolled. The mean diagnostic delay was 10 months. No statistically significant associations were observed between diagnostic delay and age, gender, symptom presence, smoking habits, or definitive diagnosis. In contrast, diagnostic delay was significantly higher in private oral health centre patients (11.19 months vs. 8.75 months p < 0.05) and in patients living more than 34 km from the diagnostic centre (p < 0.05).

CONCLUSIONS: Proximity to specialized diagnostic centres and the type of centre (public vs. private) were identified as determinants to reduce diagnostic delay in patients with desquamative gingivitis.

PMID:41853924 | DOI:10.1111/odi.70276