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Background and Aims: Body composition has been linked with clinical and prognostic outcomes in patients with cancer and cardiovascular diseases. Body composition analysis in lung cancer screening (LCS) is very limited. This study aimed at assessing the association of subcutaneous fat volume (SFV) and subcutaneous fat density (SFD), measured on chest ultra-low dose computed tomography (ultra-LDCT) images by a fully automated artificial intelligence (AI)-based software, with clinical and anthropometric characteristics in a LCS population., Methods and Results: Demographic, clinical, and dietary data were obtained from the written questionnaire completed by each participant at the first visit, when anthropometric measurements, blood sample collection and chest ultra-LDCT were performed. Images were analyzed for automated 3D segmentation of subcutaneous fat and muscle. The analysis included 938 volunteers (372 females); men with a smoking history of ≥40 pack-years had higher SFV (p = 0.0009), while former smokers had lower SFD (p = 0.0019). In female participants, SFV and SFD differed significantly according to age. SFV increased with rising BMI, waist circumference, waist-hip ratio, and CRP levels ≥2 mg/L (p < 0.0001), whereas SFD decreased with rising BMI, waist circumference, waist-hip ratio, and CRP levels ≥2 mg/L (p < 0.001) in both sexes. SFV was associated with glycemia and triglycerides levels (p = 0.0067 and p=<0.0001 in males, p = 0.0074 and p < 0.0001 in females, respectively), while SFD with triglycerides levels (p < 0.0001)., Conclusion: We observed different associations of SFV and SFD with age and smoking history between men and women, whereas the association with anthropometric data, CRP, glycemia and triglycerides levels was similar in the two sexes., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.) more...

Purpose: This study aims to determine whether longitudinal changes in CT radiomic features (RFs) and systemic inflammatory indices outperform single-time-point assessment in predicting survival in advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs)., Materials and Methods: We retrospectively acquired pretreatment (T0) and first disease assessment (T1) RFs and systemic inflammatory indices from a single-center cohort of stage IV NSCLC patients and computed their delta (Δ) variation as [(T1-T0)/T0]. RFs from the primary tumor were selected for building baseline-radiomic (RAD) and Δ-RAD scores using the linear combination of standardized predictors detected by LASSO Cox regression models. Cox models were generated using clinical features alone or combined with baseline and Δ blood parameters and integrated with baseline-RAD and Δ-RAD. All models were 3-fold cross-validated. A prognostic index (PI) of each model was tested to stratify overall survival (OS) through Kaplan-Meier analysis., Results: We included 90 ICI-treated NSCLC patients (median age 70 y [IQR=42 to 85], 63 males). Δ-RAD outperformed baseline-RAD for predicting OS [c-index: 0.632 (95%CI: 0.628 to 0.636) vs. 0.605 (95%CI: 0.601 to 0.608) in the test splits]. Integrating longitudinal changes of systemic inflammatory indices and Δ-RAD with clinical data led to the best model performance [Integrated-Δ model, c-index: 0.750 (95% CI: 0.749 to 0.751) in training and 0.718 (95% CI: 0.715 to 0.721) in testing splits]. PI enabled significant OS stratification within all the models ( P -value <0.01), reaching the greatest discriminative ability in Δ models (high-risk group HR up to 7.37, 95% CI: 3.9 to 13.94, P <0.01)., Conclusion: Δ-RAD improved OS prediction compared with single-time-point radiomic in advanced ICI-treated NSCLC. Integrating Δ-RAD with a longitudinal assessment of clinical and laboratory data further improved the prognostic performance., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.) more...

Objectives: To assess the consistency of automated measurements of coronary artery calcification (CAC) burden and emphysema extent on computed tomography (CT) images acquired with different radiation dose protocols in a lung cancer screening (LCS) population., Materials and Methods: The patient cohort comprised 361 consecutive screenees who underwent a low-dose CT (LDCT) scan and an ultra-low-dose CT (ULDCT) scan at an incident screening round. Exclusion criteria for CAC measurements were software failure and previous history of CVD, including coronary stenting, whereas for emphysema assessment, software failure only. CT images were retrospectively analyzed by a fully automated AI software for CAC scoring, using three predefined Agatston score categories (0-99, 100-399, and ≥ 400), and emphysema quantification, using the percentage of low attenuation areas (%LAA). Demographic and clinical data were obtained from the written questionnaire completed by each participant at the first visit. Agreement for CAC and %LAA categories was measured by the k-Cohen Index with Fleiss-Cohen weights (K w ) and Intraclass Correlation Coefficient (ICC) with 95% Confidence Interval (CI)., Results: An overlap of CAC strata was observed in 275/327 (84%) volunteers, with an almost perfect agreement (K w = 0.86, 95% CI 0.82-0.90; ICC = 0.86, 95% CI 0.79-0.90), while an overlap of %LAA strata was found in 204/356 (57%) volunteers, with a moderate agreement (K w = 0.57, 95% CI 0.51-0.63; ICC = 0.57, 95% CI 0.21-0.75)., Conclusion: Automated CAC quantification on ULDCT seems feasible, showing similar results to those obtained on LDCT, while the quantification of emphysema tended to be overestimated on ULDCT images., Key Points: Question Evidence demonstrating that coronary artery calcification and emphysema can be automatedly quantified on ultra-low-dose chest CT is still awaited. Findings Coronary artery calcification and emphysema measurements were similar among different CT radiation dose protocols; their automated quantification is feasible on ultra-low-dose CT. Clinical relevance Ultra-low-dose CT-based LCS might offer an opportunity to improve the secondary prevention of cardiovascular and respiratory diseases through automated quantification of both CAC burden and emphysema extent., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Ugo Pastorino. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors has significant statistical expertise. Informed consent: Written informed consent was not required for this study because the original written informed consent of the BioMILD trial allowed the use of data for future research. Ethical approval: Institutional Review Board approval was not required because the original Institutional Review Board approval obtained for the BioMILD trial was extended to this research. Study subjects or cohorts overlap: Some study subjects or cohorts have been previously reported in Milanese et al [14]. Methodology: Retrospective Observational Performed at one institution, (© 2024. The Author(s).) more...

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinico-pathological, radiomic and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in advanced NSCLC patients undergoing immune checkpoints inhibitors., Experimental Design: On 105 consecutive IO-treated advanced NSCLC, PB immunophenotypes, cytokines and CT-derived radiomic features (RFs), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and first disease assessment (T1, 9-12 weeks), and their delta (Δ) variation [(T1-T0)/T0] computed. AR, defined as progression after initial response (complete/partial) or stable disease ≥ 6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3). Clinico-pathological, PB and radiomic parameters and survival outcome were statistically correlated to AR patterns., Results: OligoAR and sysAR involved 24% and 12.4% of cases, respectively. While baseline PB immune profiles were comparable, a Δpos cytotoxic (NK, CD8+GnzB+) and Δneg immunosuppressive (CD14+ monocytes) dynamic coupled with different modulation of IL-6, TGF-β1, TNFα and sPD-L1 represented distinctive features of oligoAR vs sysAR (P<0.05). Significantly longer post-progression survival characterized oligoAR vs sysAR (median 20.3 vs 5.6 months;HR:0.22,P<0.001). The number and sites of oligoAR involvement appeared to condition blood immune background (P<0.05) and survival. Delta radiomic outperformed baseline RFs, with 15 ΔRFs sharply discriminating oligoAR from sysAR (P range:<0.001-0.04). ROC analysis confirmed the optimal performance of top-ranked ΔRFs (AUC range:0.88-0.99)., Conclusions: Longitudinal analysis of blood immune hallmarks and radiomic descriptors may decipher distinct patterns of AR to IO in advanced NSCLC patients. more...

Renal cell carcinoma (RCC) is the most common type of kidney cancer arising from renal tubular epithelial cells and is characterized by a high aggressive behavior and invasiveness that lead to poor prognosis and high mortality rate. Diagnosis of RCC is generally incidental and occurs when the stage is advanced and the disease is already metastatic. The management of RCC is further complicated by an intrinsic resistance of this malignancy to chemotherapy and radiotherapy, which aggravates the prognosis. For these reasons, there is intense research focused on identifying novel biomarkers which may be useful for a better prognostic assessment, as well as molecular markers which could be utilized for targeted therapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that has been identified as a key modulator of oxidative stress response, and its overexpression is considered a negative prognostic feature in several types of cancers including RCC, since it is involved in various key cancer-promoting functions such as proliferation, anabolic metabolism and resistance to chemotherapy. Given the key role of Nrf2 in promoting tumor progression, this enzyme could be a promising biomarker for a more accurate prediction of RCC course and it can also represent a valuable therapeutic target. In this review, we provide a comprehensive literature analysis of studies that have explored the role of Nrf2 in RCC, underlining the possible implications for targeted therapy. more...

Background: While immune checkpoint inhibitors (ICIs) are increasingly reshaping the therapeutic landscape of non-small-cell lung cancer (NSCLC), only a limited proportion of patients achieve a relevant and long-lasting benefit with these treatments, calling for the identification of clinical and, ideally modifiable, predictors of efficacy. Body composition phenotypes may reflect aspects of patients' immunology and thereby their ability to respond to ICIs. This study aims to explore the possible association between pre-treatment body composition phenotypes, tumour response, and clinical outcomes in patients receiving first-line pembrolizumab monotherapy for advanced NSCLC., Methods: A retrospective review of consecutive patients with treatment-naïve NSCLC and PD-L1 expression ≥50% undergoing pembrolizumab at three academic institutions was performed. Pre-treatment body composition parameters were measured at the third lumbar vertebra level by computed tomography, defined using pre-established cut-offs. Primary endpoint was objective response rate (ORR), secondary endpoints progression-free survival and overall survival (PFS and OS), compared through the log-rank test and the Cox proportional hazards model., Results: Data from 134 patients (93 males [69.4%] and 41 females [30.6%]) were collected. Median age was 69 years (range 36-85), with a median follow-up of 12 months (range 1-131). The median body mass index (BMI) was 24.5 (IQR 21.5; 26.1) kg/m 2 . Overall, 59.0% and 51.5% of patients met established radiographic criteria for evidence of sarcopenia and myosteatosis, respectively, which occur across the BMI spectrum. Multivariate regression analysis, adjusted for co-morbidities, revealed that sarcopenia (aOR 5.56, 95% CI. 2.46-12.6, P < 0.0001) and low intermuscular adipose tissue (IMAT) area (aOR 1.83, 95% CI. 1.22-2.83, P = 0.001) were associated with a lower rate of ORR (30.4% vs. 70.5%, P < 0.0001 and 30.7% vs. 73.2%, P < 0.0001, respectively). Moreover, both in univariate and multivariate analysis, adjusted for co-morbidities, low performance status according to the Eastern Cooperative Oncology Group scale (ECOG PS), sarcopenia and low IMAT were significantly related to short PFS (ECOG PS: aHR 2.73, 95% CI 1.60-4.66, P < 0.0001; sarcopenia: aHR 2.24, 95% CI 1.37-3.67, P = 0.001; IMAT depot: aHR 2.26, 95% 1.40-3.63, P = 0.002) and OS (ECOG PS: aHR 3.44, 95% CI 1.96-6.01, P < 0.0001; sarcopenia: aHR 4.68, 95% CI 2.44-8.99, P < 0.0001; IMAT depot: aHR 3.18, 95% 1.72-5.88, P < 0.0001)., Conclusions: Skeletal muscle abnormalities, apparently frequent in NSCLC, potentially represent intriguing predictive markers of response to ICIs and survival outcomes. Large prospective trials are needed to validate ICIs responders' clinical biomarkers., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.) more...

Lactococcus garvieae has been considered for a long time the only causal agent of lactococcosis. In recent years, different papers reported the involvement of other two bacterial species: Lactococcus petauri and Lactococcus formosensis . A different host tropism has been described for these species where L. garvieae and L. petauri are predominant species in fish and humans' infections, while L. formosensis in bovine. L. garvieae has been reported as rare infectious agent in dog. This paper represents the first isolation of L. petauri in two domesticated dog cases from urine and skin samples, respectively. The recovered L. petauri has been identified using PCR and sequencing based on Internal Transcribe Spacer (ITS) and phylogenetic analysis showed that it belongs to the L. petauri cluster with a 100% of identity with sequences previously reported from fish isolates while there were differences with L. petauri isolated from urinary tract infection from humans. L. petauri in human infection has been considered not necessarily deriving from the ingestion of contaminated food but rather as an opportunistic pathogen colonization intestinal tract. Differences among virulotypes have been reported for humans and dogs, and a comparison was also made between the virulotyping of L. petauri and L. garvieae in dogs. The antimicrobial pattern showed susceptibility for the election treatment molecules. These data contribute to our understanding of the host trophism of this species which was misclassified for long time and provide new data on its virulence factors and antimicrobial resistance. more...

Background Interstitial lung abnormalities (ILAs) are incidental CT findings suggesting early interstitial lung disease. However ILA prevalence data are scarce in an unselected routine clinical setting. Purpose To evaluate the prevalence, underreporting rate, and potential clinical impact of ILAs recognizable on either abdominal CT scans or thoracoabdominal CT scans in a routine clinical setting of unselected patients. Materials and Methods Consecutive abdominal or thoracoabdominal CT scans from unselected inpatients and outpatients (age, ≥50 years; without any available prior chest CT and no clinical history of disease against the diagnosis of ILA) from a single-center tertiary hospital between January 2008 and December 2015 were retrospectively reviewed for the presence of ILAs and compared with the original clinical reports from the CT scans. Radiologic progression of ILA was evaluated by comparing consecutive CT points. Multivariable models adjusted for age, sex, race/ethnicity, oncologic disease, and cardiovascular disease were used to assess factors associated with odds of ILAs progression and all-cause and cause-specific mortality. Results Among 21 118 patients (median age, 72 years [IQR, 64-80 years]; 11 028 [52.2%] female patients), ILAs were observed in 362 (1.7%) patients, notably in 222 (1.0%) patients who had fibrotic features at CT. ILAs were recognized in 122 of 9415 (1.3%) and 240 of 11 703 (2.1%) of abdominal and thoracoabdominal CT scans, respectively. Of available original reports for 360 patients, 158 (43.9%) of all ILAs were not originally reported. Traction bronchiectasis index was the CT factor associated with higher odds of ILA progression (odds ratio, 3.47; 95% CI: 1.83, 6.58; P < .001). Fibrotic ILAs had a fourfold higher risk of respiratory-cause mortality (hazard ratio, 4.01; 95% CI: 2.02, 7.92; P < .001) compared with patients without ILAs. Conclusion The prevalence of ILAs was 1.7% in a large, unselected sample of patients who underwent either abdominal or thoracoabdominal CT for various clinical indications. Despite their prognostic significance, 43.9% of ILAs were unreported. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hata in this issue. more...

Background: The management of subsolid nodules (SSNs) in lung cancer screening (LCS) is still a topic of debate, with no current uniform strategy to deal with these lesions at risk of overdiagnosis and overtreatment. The BioMILD LCS trial has implemented a prospective conservative approach for SSNs, managing with annual low-dose computed tomography nonsolid nodules (NSNs) and part-solid nodules (PSNs) with a solid component <5 mm, regardless of the size of the nonsolid component. The present study aims to determine the lung cancer (LC) detection and survival in BioMILD volunteers with SSNs., Materials and Methods: Eligible participants were 758 out of 4071 (18.6%) BioMILD volunteers without baseline LC and at least one SSN detected at the baseline or further low-dose computed tomography rounds. The outcomes of the study were LC detection and long-term survival., Results: A total of 844 NSNs and 241 PSNs were included. LC detection was 3.7% (31 out of 844) in NSNs and 7.1% (17 out of 241) in PSNs, being significantly greater in prevalent than incident nodules (8.4% versus 1.3% in NSNs; 14.1% versus 2.1% in PSNs; p-value for both nodule types p<0.01). Most LCs from SSNs were stage I (42/48, 87.5%), resectable (47/48, 97.9%), and caused no deaths. The 8-year cumulative survival of volunteers with LC derived from SSNs and not derived from SSNs was 93.8% and 74.9%, respectively., Conclusion: Conservative management of SSNs in LCS enables timely diagnosis and treatment of LCs arising from SSNs while ensuring the resection of more aggressive LCs detected away from SSNs., Competing Interests: Conflict of interest: R.E. Ledda reports consulting fees from Brainomix Limited and lecture honoraria from Boehringer Ingelheim outside the submitted work. Conflict of interest: N. Sverzellati reports consulting fees from Chiesi, AstraZeneca and Coreline; lecture honoraria from Boehringer Ingelheim, Chiesi and AstraZeneca; travel support from Bracco; and advisory board participation from AstraZeneca and Boehringer Ingelheim, all outside the submitted work. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.) more...

Pralsetinib and selpercatinib are two highly potent and selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment with one RET inhibitor after failure of the other is generally not recommended because of cross-resistance mechanisms. We report the case of a patient affected by metastatic RET-rearranged non-small cell lung cancer who experienced long-lasting disease control with pralsetinib. After 13 months from treatment start, the patient developed recurrent drug-related pneumonitis, requiring temporary interruptions and dose reductions and eventually failing to control the disease. Selpercatinib was then started as an off-label treatment, allowing both clinical and radiological intracranial disease control. Selpercatinib was well-tolerated at full dosage, and no pulmonary event occurred. In our case report, after pralsetinib dose reduction due to pulmonary toxicity, the therapeutic switch to selpercatinib allowed the patient to receive a full-dose treatment, eventually restoring disease control. Our case report and a few literature data suggest that switching from pralsetinib to selpercatinib may represent a therapeutic opportunity, especially for patients with brain metastases., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.) more...

Aim: The comparison between chest x-ray (CXR) and computed tomography (CT) images is commonly required in clinical practice to assess the evolution of chest pathological manifestations. Intrinsic differences between the two techniques, however, limit reader confidence in such a comparison. CT average intensity projection (AIP) reconstruction allows obtaining "synthetic" CXR (s-CXR) images, which are thought to have the potential to increase the accuracy of comparison between CXR and CT imaging. We aim at assessing the diagnostic performance of s-CXR imaging in detecting common pleuro-parenchymal abnormalities., Materials and Methods: 142 patients who underwent chest CT examination and CXR within 24 hours were enrolled. CT was the standard of reference. Both conventional CXR (c-CXR) and s-CXR images were retrospectively reviewed for the presence of consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion by 3 readers in two separate sessions. Sensitivity, specificity, accuracy and their 95% confidence interval were calculated for each reader and setting and tested by McNemar test. Inter-observer agreement was tested by Cohen's K test and its 95%CI., Results: Overall, s-CXR sensitivity ranged 45-67% for consolidation, 12-28% for nodule/mass, 17-33% for linear opacities, 2-61% for reticular opacities, and 33-58% for pleural effusion; specificity 65-83%, 83-94%, 94-98%, 93-100% and 79-86%; accuracy 66-68%, 74-79%, 89-91%, 61-65% and 68-72%, respectively. K values ranged 0.38-0.50, 0.05-0.25, -0.05-0.11, -0.01-0.15, and 0.40-0.66 for consolidation, nodule/mass, linear opacities, reticular opacities, and pleural effusion, respectively., Conclusion: S-CXR images, reconstructed with AIP technique, can be compared with conventional images in clinical practice and for educational purposes., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.) more...

Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal tumor. Despite recent advances in identifying novel target molecules, the prognosis of patients with ccRCC continues to be poor, mainly due to the lack of sensitivity to chemo- and radiotherapy and because of one-third of renal cell carcinoma patients displays metastatic disease at diagnosis. Thus, identifying new molecules for early detection and for developing effective targeted therapies is mandatory. In this work, we focused on paraoxonase-2 (PON2), an intracellular membrane-bound enzyme ubiquitously expressed in human tissues, whose upregulation has been reported in a variety of malignancies, thus suggesting its possible role in cancer cell survival and proliferation. To investigate PON2 involvement in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short harpin RNAs targeting PON2 transcript and the impact of PON2 silencing on cell viability, migration, and response to chemotherapeutic treatment was then explored. Our results showed that PON2 downregulation was able to trigger a decrease in proliferation and migration of ccRCC cells, as well as an enhancement of cell sensitivity to chemotherapy. Thus, taken together, data reported in this study suggest that the enzyme may represent an interesting therapeutic target for ccRCC., (© 2024 Wiley Periodicals LLC.) more...

Purpose: To evaluate the clinical and aesthetic outcome of percutaneous injection of sclerosant agents to treat head and neck cystic malformations (HNCM) and to assess their recurrence rate based on histology and site., Methods: Fifty-four subjects (mean age 46 years) with HNCM treated by percutaneous injection of sclerosant agents between January and December 2017 were included. Imaging and clinical data before and after the procedure were collected. Quality of Life Index, Pain Visual Analogue Scale, and Aesthetic Scale scores were measured to assess clinical and aesthetic outcomes. A size reduction of ≥ 70% assessed through the visual scale was considered significant., Results: Of the 54 HNCM, there were 26 (48%) lymphatic malformations (LM), 13 (24%) salivary epithelial duct cysts of the parotid gland, 12 (22%) salivary mucoceles, and 3 (5%) branchial cysts. A significant size reduction and a satisfactory clinical-aesthetic outcome were observed in all types of LM. The number of reinterventions was significantly associated with the number of lesions (p < 0.001). The lowest number of interventions was observed in macrocystic lymphatic malformations (average of 1.2 interventions). All salivary epithelial duct cysts showed a significant reduction in size, a satisfactory clinical-aesthetic outcome, and an average of 1.16 interventions per patient. Mucoceles had a worse response, with only 3/14 patients showing a satisfactory and long-lasting clinical outcome (average of 1.16 interventions). Treatment of branchial cysts showed the worst outcome with a limited clinical response (3/3)., Conclusion: Percutaneous injection of sclerosant agents may be considered as a first-line treatment for LM and salivary epithelial duct cysts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...