No evidence for the superiority of 3 T MRI over 1.5 T MRI for diagnosing wrist ligamentous lesions: a systematic review and meta-analysis.

PURPOSES: Our aim was to determine the diagnostic accuracy of native MRI regarding different ligamentous lesions of the wrist and to analyze the influence of technical characteristics, such as field strength, application of fat saturation, 3D sequences, and wrist coils. METHODS: The systematic search was performed using MEDLINE, Embase, and CENTRAL databases. Studies that were published before the 12th of February 2024 were included. All studies comparing the diagnostic accuracy of native wrist MRI to that of wrist arthroscopy for suspected ligamentous lesions were included. Results were analyzed by anatomic localization and technical aspects of the MRI. To assess the quality of included studies, we used the revised QUADAS-2 tool. RESULTS: The systematic search revealed 5,181 articles. Thirty-seven studies, reporting 3893 ligamentous lesions, were eligible for inclusion. The studies displayed heterogeneity in terms of technical conditions, such as field strength, the use of wrist coils, the application of 3D sequences and fat saturation. Research methods also varied. Overall sensitivity and specificity were 0.78 (0.66 - 0.86) and 0.81 (0.70 - 0.89) for 1.5T MRI, while sensitivity was 0.73 (0.68 - 0.78) and specificity was 0.90 (0.59 - 0.98) for 3T MRI. There was no significant difference between the two subgroups (p=0,3807 and p=0,4248). Sensitivity was 0.82 (0.75 - 0.87) for triangular fibrocartilage complex (TFCC) lesions, 0.63 (0.50 - 0.74) for scapholunate ligament (SL) tears, and 0.41 (0.25 - 0.60) for lunotriquetral ligament (LT) lesions. Specificity for TFCC lesions was 0.82 (0.73 - 0.89), for SL tears 0.86 (0.73 - 0.93), and for LT lesions 0.93 (0.81 - 0.98). CONCLUSION: The sensitivity and specificity of MRI is influenced by the anatomic location of the lesion and technical conditions. In terms of diagnostic accuracy, no significant difference was found between 1.5T and 3T MRI. LEVEL OF EVIDENCE: III. Systematic review of Level II. - III.

RICTOR amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma.

RICTOR gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. RICTOR amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare RICTOR amplification detected by fluorescence in situ hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung. The study was complemented by analysis of the publicly available Lung Squamous Cell Carcinoma (TCGA, Firehose legacy) dataset. RICTOR amplification was observed in 20% of our cases and 16% of the lung SCC cases of the TCGA dataset. Rictor and PD-L1 expression was seen in 74% and 44% of the cases, respectively. Rictor IHC showed two staining patterns: membrane staining (16% of the cases) and cytoplasmic staining (58% of the cases). Rictor membrane staining predicted RICTOR amplification as detected by FISH with high specificity (95%) and sensitivity (70%). We did not find any correlation between RICTOR amplification and PD-L1 expression; RICTOR amplification was detected in 18% and 26% of PD-L1 positive and negative cases, respectively. The TCGA dataset analysis showed similar results; RICTOR copy number correlated with Rictor mRNA and protein expression but showed no association with PD-L1 mRNA and protein expression. In conclusion, the correlation between RICTOR amplification and Rictor membrane staining suggests that the latter can potentially be used as a surrogate marker to identify lung SCC cases with RICTOR amplification. Since a significant proportion of PD-L1 negative SCC cases harbor RICTOR amplification, analyzing PD-L1 negative tumors by RICTOR FISH or Rictor IHC can help select patients who may benefit from mTORC2 inhibitor therapy.

Multibiomarker disease activity score: an objective tool for monitoring rheumatoid arthritis? A systematic review and meta-analysis.

OBJECTIVES: The multibiomarker disease activity (MBDA) score is an objective tool for monitoring disease activity in RA. Here we report a systematic review and meta-analysis of the clinical value of the MBDA score in RA. METHODS: We performed a systematic literature search in five medical databases-MEDLINE (via PubMed), Cochrane Library (CENTRAL), Embase, Scopus and Web of Science-from inception to 13 October 2021. Original articles reporting on the performance of the MBDA score's correlation with conventional disease activity measures or the predictive and discriminative values of the MBDA score for radiographic progression, therapy response, remission and relapse were included. RESULTS: Our systematic search provided a total of 1190 records. After selection and citation searches, we identified 32 eligible studies. We recorded moderate correlations between MBDA score and conventional disease activity measures at baseline [correlation (COR) 0.45 (CI 0.28, 0.59), I2 = 71.0% for the 28-joint DAS with CRP (DAS28-CRP) and COR 0.55 (CI 0.19, 0.78), I2 = 0.0% for DAS28 with ESR] and at follow-up [COR 0.44 (CI 0.28, 0.57, I2 = 70.0% for DAS28-CRP) and found that the odds of radiographic progression were significantly higher for patients with a high baseline MBDA score (>44) than for patients with a low baseline MBDA score (<30) [OR 1.03 (CI 1.02-1.05), I2 = 10.0%]. CONCLUSION: The MBDA score might be used as an objective disease activity marker. In addition, it is also a reliable prognostic marker of radiographic progression.

An Observational Study on the Molecular Profiling of Primary Melanomas Reveals a Progression Dependence on Mitochondrial Activation.

Melanoma in advanced stages is one of the most aggressive tumors and the deadliest of skin cancers. To date, the histopathological staging focuses on tumor thickness, and clinical staging is a major estimate of the clinical behavior of primary melanoma. Here we report on an observational study with in-depth molecular profiling at the protein level including post-translational modifications (PTMs) on eleven primary tumors from melanoma patients. Global proteomics, phosphoproteomics, and acetylomics were performed on each sample. We observed an up-regulation of key mitochondrial functions, including the mitochondrial translation machinery and the down-regulation of structural proteins involved in cell adhesion, the cytoskeleton organization, and epidermis development, which dictates the progression of the disease. Additionally, the PTM level pathways related to RNA processing and transport, as well as chromatin organization, were dysregulated in relation to the progression of melanoma. Most of the pathways dysregulated in this cohort were enriched in genes differentially expressed at the transcript level when similar groups are compared or metastasis to primary melanomas. At the genome level, we found significant differences in the mutation profiles between metastatic and primary melanomas. Our findings also highlighted sex-related differences in the molecular profiles. Remarkably, primary melanomas in women showed higher levels of antigen processing and presentation, and activation of the immune system response. Our results provide novel insights, relevant for developing personalized precision treatments for melanoma patients.