A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion.

Dense and aligned Collagen I fibers are associated with collective cancer invasion led by protrusive tumor cells, leader cells. In some breast tumors, a population of cancer cells (basal-like cells) maintain several epithelial characteristics and express the myoepithelial/basal cell marker Keratin 14 (K14). Emergence of leader cells and K14 expression are regarded as interconnected events triggered by Collagen I, however the underlying mechanisms remain unknown. Using breast carcinoma organoids, we show that Collagen I drives a force-dependent loop, specifically in basal-like cancer cells. The feed-forward loop is centered around the mechanotransducer Yap and independent of K14 expression. Yap promotes a transcriptional program that enhances Collagen I alignment and tension, which further activates Yap. Active Yap is detected in invading breast cancer cells in patients and required for collective invasion in 3D Collagen I and in the mammary fat pad of mice. Our work uncovers an essential function for Yap in leader cell selection during collective cancer invasion.

The extracellular matrix as hallmark of cancer and metastasis: From biomechanics to therapeutic targets.

The extracellular matrix (ECM) is essential for cell support during homeostasis and plays a critical role in cancer. Although research often concentrates on the tumor's cellular aspect, attention is growing for the importance of the cancer-associated ECM. Biochemical and physical ECM signals affect tumor formation, invasion, metastasis, and therapy resistance. Examining the tumor microenvironment uncovers intricate ECM dysregulation and interactions with cancer and stromal cells. Anticancer therapies targeting ECM sensors and remodelers, including integrins and matrix metalloproteinases, and ECM-remodeling cells, have seen limited success. This review explores the ECM's role in cancer and discusses potential therapeutic strategies for cell-ECM interactions.

Splenic Artery Infectious Aneurysms in Infective Endocarditis - An Observational Study and Comprehensive Literature Review.

BACKGROUND: To determine the prevalence, the clinical and radiological features, associated factors, treatment, and outcome of splenic artery aneurysms (SAAs) in infective endocarditis (IE). METHODS: We retrospectively reviewed 474 consecutive patients admitted to our institution with definite IE (2005-2020). RESULTS: Six patients had SAAs (1.3%; 3 women; mean age: 50 years). In all cases, the diagnosis was obtained by abdominal computed tomography angiography (CTA). SAAs-IE were solitary and saccular with a mean diameter of 30 mm (range: 10-90 mm). SAAs-IE were intrasplenic (n = 4) or hilar (n = 2). Streptococcus spp. were the predominant organisms (n = 4). In all cases, a left-sided native valve was involved (aortic, n = 3; mitral, n = 2; mitral-aortic, n = 1). SAAs were silent in half patients and were revealed by abdominal pain (n = 2) and by the resurgence of fever after cardiac surgery (n = 1). All patients underwent emergent valve replacement. One patient died within 24 hr from multiorgan failure. For the others, uneventful coil embolization was performed in 4 patients after valve replacement (3 diagnosed early and 1 at 8 weeks). In the remaining patient, SAA-IE diagnosed at abdominal CTA at day 16, with complete resolution under appropriate antibiotherapy alone. CONCLUSIONS: SAAs-IE are a rare occurrence that may be clinically silent. SAAs-IE can be intrasplenic or hilar in location. Endovascular treatment in this context was safe. According to current guidelines, radiologic screening by abdominal CTA allowed the detection of silent SAAs which could be managed by endovascular treatment to prevent rupture. The delayed formation of these SAAs could justify a CTA control at the end of antibiotherapy.

Hemoptysis: From Diagnosis to Treatment.

Management of hemoptysis begins with an angio-CT to identify the location, the bleeding vessel, mapping of systemic arteries and the cause of the hemoptysis. Endovascular treatment is the first-line therapy, in 90% of cases by embolization of the systemic arteries and in 10% of cases by occlusion of the pulmonary arteries.

Ultrasonography in thoracic and abdominal stab wound injury: results from the FETTHA study.

BACKGROUND: While the role of Extended Focused Assessment with Sonography in Trauma (eFAST) is well defined in the management of severe blunt trauma, its performance in injuries caused by stab wounds has been poorly assessed. METHODS: Prospective single centre study which included all patients with stab wounds to the thorax or abdomen between December 2016 and December 2018. All patients underwent initial investigation with both eFAST and CT scan, except in cases of haemodynamic or respiratory instability, and in cases with a positive diagnosis by eFAST in which case surgery without CT scan was performed. RESULTS: Of the 200 consecutive patients included, 14 unstable patients underwent surgery immediately after eFAST. In these 14 patients, 9 had cardiac tamponade identified by eFAST and all were confirmed by surgery. In the remaining 186 patients, the median time between eFAST and CT scan was 30 min (IQR 20-49 min). Test characteristics (including 95% CI) for eFAST compared with reference standard of CT scan for detecting pneumothorax were as follows: sensitivity 77% (54%-92%), specificity 93% (90%-97%), positive predictive value (PPV) 60% (49%-83%), negative predictive value (NPV) 97% (93%-99%). Test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemothorax were as follows: sensitivity 97% (74%-99%), specificity 96% (92%-98%), PPV 83% (63%-93%) and NPV 99% (96%-100%). Finally, test characteristics (including 95% CI) for eFAST compared with CT scan for detecting haemoperitoneum were as follows: sensitivity 75% (35%-97%), specificity 97% (93%-99%), PPV 55% (23%-83%) and NPV 99% (96%-99%). CONCLUSIONS: In patients admitted with stab wounds to the torso, eFAST was not sensitive enough to diagnose pneumothorax and haemoperitoneum, but performed better in the detection of cardiac tamponade and haemothorax than the other injuries. More robust multicentre studies are needed to better define the role of eFAST in this specific population.

Multimodal Techniques to Study Tumor Growth, Basement Membrane Breaching, and Invasion in 3D Matrices.

Cancer-derived organoids and three-dimensional (3D) extracellular matrix (ECM) are taking center stage as in vitro models to study neoplastic cell behavior, since they recapitulate the heterogeneous cellular composition of tumors and their extracellular environment. In combination with imaging and molecular/biochemical techniques, 3D organoid models have contributed substantially to our knowledge about the cellular and molecular mechanisms that regulate the growth of tumors and invasion into the surrounding tissue. We here outline a set of protocols that describe culturing of cancer-derived organoids in 3D matrices and various strategies that allow modeling of tumor growth, tumor cell penetration into basement membranes, and invasion into Collagen I-rich ECM. Furthermore, we specify protocols for subsequent handling of organoids cultured in 3D ECM for confocal microscopy and analysis of gene expression at the protein and mRNA level. Although we here use breast cancer-derived organoids, these protocols can be directly applied or adapted for organoids derived from other cancer types or healthy tissues. Thus, in addition to investigating cell behavior of multiple cancer types, the combination of protocols described here may be used to study processes such as cell differentiation and migration during homeostasis and normal development.

Breast metastasis of a lung carcinoma.

Breast metastasis is a rare phenomenon (0.2-1.3%)1 compared to primary breast lesions. Several neoplasms have been reported to metastasize to the breast such as melanoma, lymphoma and lung cancer. In this article, we report a case of breast metastasis of lung cancer confirmed by biopsy and immunohistochemistry with CT and ultrasound imaging.

Grade 3-4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study.

Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3−4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3−4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7−13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2−0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC.

Staple Line Intrathoracic Migration After Sleeve Gastrectomy: Correlation between Symptoms, CT Three-Dimensional Stomach Analysis, and 24-h pH Monitoring.

PURPOSE: Migration of the staple line is the definition of sliding hiatus hernia in sleeve gastrectomy patients. The main aim was to determine the frequency and measurement of intrathoracic staple line migration and its correlation with GERD symptoms and pH monitoring. MATERIALS AND METHODS: This was a prospective clinical trial including all patients who underwent sleeve gastrectomy more than 1 year previously. All the patients underwent computed tomography (CT) imaging, and migration of the proximal end of the suture above the level of the hiatus was measured in mm. All the patients with symptoms suggestive of GERD were assessed using the GERD impact scale (GIS), and wireless 24-h esophageal pH and symptom association monitoring (SAP) were carried out. Analysis of risk factors for postoperative staple line migration was performed. RESULTS: Between March 2018 and December 2018, 194 patients were evaluated (mean age 45.1 ± 11.2 years; 161 females); 88/194 (45.4%) presented an average intrathoracic migration of 16.2 ± 6.9 mm. Thirty-eight of 194 (19.5%) patients presented symptoms suggestive of gastroesophageal reflux. There was a significant relationship between staple line intrathoracic migration and postsleeve GERD symptomatology (p = 0.0004, OR = 4.25 [1.92-9.39]). However, there was no significant correlation between positive 24-h pH monitoring and intrathoracic migration of the staple line (p = 0.1). CONCLUSION: A migration greater than 17 mm was strongly correlated with postsleeve GERD symptoms but not with positive 24-h pH monitoring.

Spatial collagen stiffening promotes collective breast cancer cell invasion by reinforcing extracellular matrix alignment.

The tumor micro-environment often contains stiff and irregular-bundled collagen fibers that are used by tumor cells to disseminate. It is still unclear how and to what extent, extracellular matrix (ECM) stiffness versus ECM bundle size and alignment dictate cancer cell invasion. Here, we have uncoupled Collagen-I bundling from stiffness by introducing inter-collagen crosslinks, combined with temperature induced aggregation of collagen bundling. Using organotypic models from mouse invasive ductal and invasive lobular breast cancers, we show that increased collagen bundling in 3D induces a generic increase in breast cancer invasion that is independent of migration mode. However, systemic collagen stiffening using advanced glycation end product (AGE) crosslinking prevents collective invasion, while leaving single cell invasion unaffected. Collective invasion into collagen matrices by ductal breast cancer cells depends on Lysyl oxidase-like 3 (Loxl3), a factor produced by tumor cells that reinforces local collagen stiffness. Finally, we present clinical evidence that collectively invading cancer cells at the invasive front of ductal breast carcinoma upregulate LOXL3. By uncoupling the mechanical, chemical, and structural cues that control invasion of breast cancer in three dimensions, our data reveal that spatial control over stiffness and bundling underlie collective dissemination of ductal-type breast cancers.

Measuring Walking Speed Failed to Predict Early Death and Toxicity in Elderly Patients with Metastatic Non-Small-Cell Lung Cancer (NSCLC) Selected for Undergoing First-Line Systemic Treatment: An Observational Exploratory Study.

Walking speed (WS) has emerged as a potential predictor of mortality in elderly cancer patients, yet data involving non-small-cell lung cancer (NSCLC) patients are scarce. Our prospective exploratory study sought to determine whether WS would predict early death or toxicity in patients with advanced NSCLC receiving first-line systemic intravenous treatment. Overall, 145 patients of ≥70 years were diagnosed with NSCLC over 19 months, 91 of whom displayed locally-advanced or metastatic cancer. As first-line treatment, 21 (23%) patients received best supportive care, 13 (14%) targeted therapy, and 57 (63%) chemotherapy or immunotherapy. Among the latter, 38 consented to participate in the study (median age: 75 years). Median cumulative illness rating scale for geriatrics (CIRS-G) was 10 (IQR: 8−12), and median WS 1.09 (IQR: 0.9−1.31) m/s. Older age (p = 0.03) and comorbidities (p = 0.02) were associated with Grade 3−4 treatment-related adverse events or death within 6 months of accrual. Overall survival was 14.3 (IQR: 6.1-NR) months for patients with WS < 1 m/s versus 17.3 (IQR: 9.2−26.5) for those with WS ≥ 1 m/s (p = 0.78). This exploratory study revealed WS to be numerically, yet not significantly, associated with early mortality in older metastatic NSCLC patients. Following these hypothesis-generating results, a larger prospective, multicenter study appears to be required to further investigate this outcome.

MRI-based kidney radiomic analysis during chronic lithium treatment.

BACKGROUND: Lithium therapy during bipolar disorder is associated with an increased risk of chronic kidney disease (CKD) that is slowly progressive and undetectable at early stages. We aimed at identifying kidney image texture features as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomics of T2-weighted magnetic resonance imaging (MRI). METHODS: One hundred and eight patients treated with lithium were evaluated including mGFR and kidney MRI, with T2-weighted sequence single-shot fast spin-echo. Computed radiomic analysis was performed after kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect an mGFR <60 ml/min/1.73 m². The texture index was validated using a training and a validation cohort. RESULTS: Texture analysis index was able to detect an mGFR decrease, with an AUC of 0.85 in the training cohort and 0.71 in the validation cohort. Patients with a texture index below the median were older (59 [42-66] vs. 46 [34-54] years, p = .001), with longer treatment duration (10 [3-22] vs. 6 [2-10] years, p = .02) and a lower mGFR (66 [46-84] vs. 83 [71-94] ml/min/1.73m², p < .001). Texture analysis index was independently and negatively associated with age (ß = -.004 ± 0.001, p < .001), serum vasopressin (-0.005 ± 0.002, p = .02) and lithium treatment duration (-0.01 ± 0.003, p = .001), with a significant interaction between lithium treatment duration and mGFR (p = .02). CONCLUSIONS: A renal texture index was developed among patients treated with lithium associated with a decreased mGFR. This index might be relevant in the diagnosis of lithium-induced renal toxicity.

Transthoracic lung biopsy for pulmonary nodules ≤20†mm in routine clinical care.

BACKGROUND: Computed tomography (CT) screening has improved lung cancer survival, yet increasingly detects small lung lesions. Thus, the number of transthoracic lung biopsies (TTLB) for small nodules is expected to rise significantly. The aim of the present study was to evaluate the diagnostic accuracy and safety of CT-guided TTLB for nodules ≤20 mm versus nodules >20 mm. STUDY DESIGN AND METHODS: Data for CT-guided TTLBs from 474 consecutive patients were prospectively collected over a 3-year period (198 lesions ≤20 mm and 276 lesions >20 mm) in a teaching hospital and analysed in terms of diagnostic performance and complications. RESULTS: There were more conclusive biopsies in the >20 mm lesion group (n=236, 85.5%) than in ≤20 mm lesion group (n=140, 70.7%; p<0.001). The overall accuracy, sensitivity, specificity and negative predictive value for diagnosing malignant lesions after first TTLB were 88.4%, 84%, 100% and 70.1%, respectively, for ≤20 mm lesions, and 94.2%, 93%, 100% and 74.6%, respectively, for >20 mm lesions. Pneumothorax requiring drainage was significantly more common for ≤20 mm lesions, compared to TTLB of larger lesions (9.6% versus 4.3%; p=0.02). Prolonged hospital stay due to pneumothorax occurred in 27 (17.4%) TTLBs of ≤20 mm lesions and 15 (7%) TTLBs of >20 mm lesions (p=0.002). There were no deaths. The only variable significantly associated with diagnostic failure in the ≤20 mm lesion group was the radiologist's experience. INTERPRETATION: TTLBs for lesions ≤20 mm were associated with slightly lower diagnostic performance, whereas the higher rate of major complications was still inferior to that extrapolated from United States insurance databases.

Clinical Impact of Surgical Lung Biopsy for Interstitial Lung Disease in a Reference Center.

BACKGROUND: Diagnosis of interstitial lung disease is based on the analysis of clinical, biological, radiological, and pathological findings during a multidisciplinary discussion (MDD). When a definitive diagnosis is not possible, guidelines recommend obtaining lung samples through surgical lung biopsy (SLB). We sought to determine morbidity, mortality, diagnostic yield, and therapeutic impact of SLB in the management of patients with interstitial lung disease. METHODS: We retrospectively analyzed morbidity, mortality, diagnostic yield, and therapeutic changes after SLB for interstitial lung disease performed electively from January 2015 to May 2019 in a reference center. Each case was reviewed during 2 MDDs, first without and then with the result of the SLB. RESULTS: The study group included 73 patients (56% male, age 66 [interquartile range (IQR), 57-70] years, forced vital capacity 79% [IQR, 69%-91%], diffusing capacity of the lungs for carbon monoxide 52% [IQR, 46%-63%]). Median postoperative hospital length of stay was 2 (IQR, 0-11) days. Thirteen (17%) patients experienced at least 1 complication, including pain at 1 month (n = 8) and residual pneumothorax (n = 6). No serious complication or postoperative death was noticed. After the first retrospective MDD, the working diagnosis was idiopathic nonspecific interstitial pneumonia in 20 (27%), idiopathic pulmonary fibrosis in 18 (25%), fibrotic hypersensitivity pneumonitis in 15 (21%), unclassifiable interstitial lung disease in 5 (7%), and other diagnosis in 15 (21%) patients. After SLB and second retrospective MDD, the final diagnosis was modified in 35 (48%) patients and led to therapeutic changes in 33 (45%) patients. CONCLUSIONS: SLB is associated with no serious complication or death and notably changes the diagnosis and treatment of interstitial lung disease.

Regulation of a progenitor gene program by SOX4 is essential for mammary tumor proliferation.

In breast cancer the transcription factor SOX4 has been shown to be associated with poor survival, increased tumor size and metastasis formation. This has mostly been attributed to the ability of SOX4 to regulate Epithelial-to-Mesenchymal-Transition (EMT). However, SOX4 regulates target gene transcription in a context-dependent manner that is determined by the cellular and epigenetic state. In this study we have investigated the loss of SOX4 in mammary tumor development utilizing organoids derived from a PyMT genetic mouse model of breast cancer. Using CRISPR/Cas9 to abrogate SOX4 expression, we found that SOX4 is required for inhibiting differentiation by regulating a subset of genes that are highly activated in fetal mammary stem cells (fMaSC). In this way, SOX4 re-activates an oncogenic transcriptional program that is regulated in many progenitor cell-types during embryonic development. SOX4-knockout organoids are characterized by the presence of more differentiated cells that exhibit luminal or basal gene expression patterns, but lower expression of cell cycle genes. In agreement, primary tumor growth and metastatic outgrowth in the lungs are impaired in SOX4KO tumors. Finally, SOX4KO tumors show a severe loss in competitive capacity to grow out compared to SOX4-proficient cells in primary tumors. Our study identifies a novel role for SOX4 in maintaining mammary tumors in an undifferentiated and proliferative state. Therapeutic manipulation of SOX4 function could provide a novel strategy for cancer differentiation therapy, which would promote differentiation and inhibit cycling of tumor cells.

Randomised trial of first-line bronchial artery embolisation for non-severe haemoptysis of mild abundance.

BACKGROUND: Whereas first-line bronchial artery embolisation (BAE) is considered standard of care for the management of severe haemoptysis, it is unknown whether this approach is warranted for non-severe haemoptysis. RESEARCH QUESTION: To assess the efficacy on bleeding control and the safety of first-line BAE in non-severe haemoptysis of mild abundance. STUDY DESIGN AND METHODS: This multicentre, randomised controlled open-label trial enrolled adult patients without major comorbid condition and having mild haemoptysis (onset <72 hours, 100-200 mL estimated bleeding amount), related to a systemic arterial mechanism. Patients were randomly assigned (1:1) to BAE associated with medical therapy or to medical therapy alone. RESULTS: Bleeding recurrence at day 30 after randomisation (primary outcome) occurred in 4 (11.8%) of 34 patients in the BAE strategy and 17 (44.7%) of 38 patients in the medical strategy (difference -33%; 95% CI -13.8% to -52.1%, p=0.002). The 90-day bleeding recurrence-free survival rates were 91.2% (95% CI 75.1% to 97.1%) and 60.2% (95% CI 42.9% to 73.8%), respectively (HR=0.19, 95% CI 0.05 to 0.67, p=0.01). No death occurred during follow-up and no bleeding recurrence needed surgery.Four adverse events (one major with systemic emboli) occurred during hospitalisation, all in the BAE strategy (11.8% vs 0%; difference 11.8%, 95% CI 0.9 to 22.6, p=0.045); all eventually resolved. CONCLUSION: In non-severe haemoptysis of mild abundance, BAE associated with medical therapy had a superior efficacy for preventing bleeding recurrences at 30 and 90 days, as compared with medical therapy alone. However, it was associated with a higher rate of adverse events. TRIAL REGISTRATION NUMBER: NCT01278199.

Radiation dose reduction with the wide-volume scan mode for interstitial lung diseases.

OBJECTIVES: The wide-volume mode, available on wide-area detector row CTs, has the advantage of reducing exposure time and radiation dose. It is infrequently used for lung diseases. The purpose of this study is to compare image quality and radiation dose of wide-volume chest CT to those of standard helical CT in the setting of interstitial lung diseases. METHODS: Retrospective monocentric study including 50 consecutive patients referred for follow-up or screening of interstitial lung diseases, requiring prone scan, acquired with the wide-volume mode, in addition to the routine supine scan, acquired with the helical mode. The optimal collimation in wide-volume mode (320 × 0.5mm or 240 × 0.5mm) was chosen according to the length of the thorax. Wide-volume acquisitions were compared to helical acquisitions for radiation dose (CTDIvol, DLP) and image quality, including analysis of normal structures, lesions, overall image quality, and artifacts (Wilcoxon signed-rank test). RESULTS: Median CTDIvol and DLP with wide volumes (3.1 mGy and 94.6 mGy·cm) were significantly reduced (p < 0.0001) as compared to helical mode (3.7mGy and 122.1 mGy·cm), leading to a median 21% and 32% relative reduction of CTDIvol and DLP, respectively. Image noise and quality were not significantly different between the two modes. Misalignment artifact at the junction of two volumes was occasionally seen in the wide-volume scans and, when present, did not impair the diagnostic quality in the majority of cases. CONCLUSIONS: Wide-volume mode allows 32% radiation dose reduction compared to the standard helical mode and could be used routinely for diagnosis and follow-up of interstitial lung diseases. KEY POINTS: • Retrospective monocentric study showed that wide-volume scan mode reduces radiation dose by 32% in comparison to helical mode for chest CT in the setting of interstitial lung diseases. • Mild misalignment may be observed at the junction between volumes with the wide-volume mode, without decrease of image quality in the majority of cases and without impairing diagnostic quality. • Wide-volume mode could be used routinely for the diagnosis and follow-up of interstitial lung diseases.

Intergroupe francophone de cancérologie thoracique, Société de pneumologie de langue française, and Société d'imagerie thoracique statement paper on lung cancer screening.

Following the American National Lung Screening Trial results in 2011 a consortium of French experts met to edit a statement. Recent results of other randomized trials gave the opportunity for our group to meet again in order to edit updated guidelines. After literature review, we provide here a new update on lung cancer screening in France. Notably, in accordance with all international guidelines, the experts renew their recommendation in favor of individual screening for lung cancer in France as per the conditions laid out in this document. In addition, the experts recommend the very rapid organization and funding of prospective studies, which, if conclusive, will enable the deployment of lung cancer screening organized at the national level.

Determinants of Kidney Function and Accuracy of Kidney Microcysts Detection in Patients Treated With Lithium Salts for Bipolar Disorder.

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection. Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences. Results: Median age was 51 [27-62] years, and median lithium treatment duration was 5 [2-14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (ß -0.8 [-1; -0.6] ml/min/1.73 m2 GFR decrease for each year of treatment), a higher age (ß -0.4 [-0.6; -0.3] ml/min/1.73 m2 for each year of age, p < 0.001), albuminuria (ß -3.97 [-6.6; -1.3], p = 0.003), hypertension (ß -6.85 [-12.6; -1.1], p = 0.02) and hypothyroidism (ß -7.1 [-11.7; -2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = -0.64, p < 0.001), but not in patients with no microcysts (r = -0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR <45 ml/min/1.73 m2 (AUC 0.893, p < 0.001, sensitivity 80%, specificity 81% for a cut-off value of five microcysts). Conclusion: Lithium treatment duration and hypothyroidism strongly impacted mGFR independently of age, especially in patients with microcysts. MRI might help detect early lithium-induced kidney damage and inform preventive strategies.

Mediastinal Masses: 18F-FDG-PET/CT Features Based on the International Thymic Malignancy Interest Group Classification.

Imaging plays a key role in the management of mediastinal masses. In an effort to standardize the analysis of the mediastinum, the International Thymic Malignancy Interest Group (ITMIG) has proposed a three compartments-based diagnostic classification, intended for clinicians and radiologists. Several articles have documented its usefulness to guide the diagnosis using cross-sectional imaging. Similarly, fluorine-18-radiolabeled fluorodeoxyglucose positron emission tomography combined to computed tomography (18F-FDG-PET/CT) can be useful in this setting, either as a first-line diagnostic technique, or in addition to cross-sectional imaging. In this article, which is thought as an aid for nuclear medicine physicians and radiologists, we aim to present, based on the ITMIG classification, the main mediastinal pathologies that can be observed with 18F-FDG-PET/CT, and the additional diagnostic value that can be expected from this technique. For this purpose, we segmented the mediastinum according to the ITMIG classification, and reviewed the available literature for each of the corresponding organs and/or disease. Given the importance of the clinical context for the interpretation of PET imaging, we presented each of the diseases according to: (1) their suggestive clinical context; (2) the suggestive features on nonenhanced CT (which is the standard in PET imaging); and (3) the typical 18F-FDG characteristics. The purpose of this article is to depict the main features of the most common mediastinal diseases that can be encountered with 18F-FDG-PET/CT, and to highlight its diagnostic value in this setting, alone or in combination with other imaging modalities.