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760-46.0), Ti (32.0-440), V ( less then 0.85-1.7) and Zn (24.90-2,600). As, Co, Mo and Se in all the investigated samples were found to be below the LoQ values of ICP OES. In this study, regardless of sample compositions and origins (Brazilian or Chinese), high levels of Al, Cd, Cr, Cu, Mn, Ni, Pb, Sb, Ti, V and Zn were observed, exceeding the recommended maximum tolerable limits, according to Brazilian and global legislations, which may present potential risks to human health and the environment.The highly conserved Nonsense-mediated mRNA decay (NMD) pathway is a translation dependent mRNA degradation pathway. Although NMD is best known for its role in degrading mRNAs with premature termination codons (PTCs) generated during transcription, splicing, or damage to the mRNAs, NMD is now also recognized as a pathway with additional important functions. Notably, NMD precisely regulates protein coding natural mRNAs, hence controlling gene expression within several physiologically significant pathways. Such pathways affected by NMD include nutritional bio-metal homeostasis and metal ion detoxification, as well as crosstalk between these pathways. Here, we focus on the relationships between NMD and various metal homeostasis and detoxification pathways. We review the described role that the NMD pathway plays in magnesium, zinc, iron, and copper homeostasis, as well as cadmium detoxification.
Intrahepatic cholangiocarcinoma (iCCA) carries a dismal prognosis and, despite increasing incidence, still lacks effective treatments. In this scenario, locoregional therapies (LRT) are gaining interest as they may be effective at local tumor control and complementary to surgical and non-surgical approaches. In this article, we will review the evolving role of LRT performed by interventional radiologists in the management of iCCA.
Accumulating retrospective evidence indicates that ablative therapies and transarterial embolizations are of benefit for iCCA with unresectable disease, demonstrating promising safety profiles and prolonged or comparable survival outcomes compared to systemic therapy and surgery. Additionally, for surgical candidates, portal ± hepatic venous embolization can improve the safety of hepatectomy by inducing preoperative hypertrophy of the non-involved liver lobe. Aminoguanidine hydrochloride clinical trial LRTs are playing an increasingly important role in the multimodal treatment of iCCA from various perspectives with reduced toxicity relative to traditional treatments. To expand the scope of applications for LRTs in this setting, future prospective randomized studies are needed to confirm their efficacy and advantage.
Accumulating retrospective evidence indicates that ablative therapies and transarterial embolizations are of benefit for iCCA with unresectable disease, demonstrating promising safety profiles and prolonged or comparable survival outcomes compared to systemic therapy and surgery. Additionally, for surgical candidates, portal ± hepatic venous embolization can improve the safety of hepatectomy by inducing preoperative hypertrophy of the non-involved liver lobe. LRTs are playing an increasingly important role in the multimodal treatment of iCCA from various perspectives with reduced toxicity relative to traditional treatments. To expand the scope of applications for LRTs in this setting, future prospective randomized studies are needed to confirm their efficacy and advantage.
To describe the biological rationale of peripheral blood cells (PBC)-derived inflammatory indexes and assess the related prognostic scores for patients with advanced non-small cell lung cancer (aNSCLC) treated with immune-checkpoint inhibitors (ICI).
Inflammatory indexes based on PBC may indicate a pro-inflammatory condition affecting the immune response to cancer. The lung immune prognostic index (LIPI), consisting of derived neutrophils-to-lymphocyte ratio (NLR) and lactate dehydrogenase, is a validated prognostic tool, especially for pretreated aNSCLC patients, where the combination of NLR and PD-L1 tumour expression might also be predictive of immunotherapy benefit. In untreated high-PD-L1 aNSCLC patients, the Lung-Immune-Prognostic score (LIPS), including NLR, ECOG PS and concomitant steroids, is prognostic, and its modified version might indicate patients with favourable outcomes despite an ECOG PS of 2. NLR times platelets (i.e., SII), included in the NHS-Lung score, might improve the prognosticatidexes and related scores represent accurate, reproducible and non-expensive prognostic tools with clinical and research utility.
In this article, we discuss recent advances in germline genetic testing for patients with breast cancer and highlight current limitations and impacts on clinical care. We also provide an update on the therapeutic implications of having a germline mutation, including targeted systemic therapy options for treating early and metastatic breast cancer.
Approximately 5 to 10% of women diagnosed with breast cancer have a pathogenic variant in a hereditary cancer susceptibility gene, which has significant implications for managing these patients. Previously, testing was done mainly to inform screening and risk-reduction treatment; however, more recently, germline genetic results have significant systemic therapy implications that can meaningfully improve outcomes in breast cancer patients, especially with oral poly-ADP-ribose polymerase (PARP) inhibitors. These systemic therapy advances implore a shift in paradigm for whom to test moving forward and how to modify the existing testing models to meet the increasing demand for germline testing, which is expected to grow exponentially.
Approximately 5 to 10% of women diagnosed with breast cancer have a pathogenic variant in a hereditary cancer susceptibility gene, which has significant implications for managing these patients. Previously, testing was done mainly to inform screening and risk-reduction treatment; however, more recently, germline genetic results have significant systemic therapy implications that can meaningfully improve outcomes in breast cancer patients, especially with oral poly-ADP-ribose polymerase (PARP) inhibitors. These systemic therapy advances implore a shift in paradigm for whom to test moving forward and how to modify the existing testing models to meet the increasing demand for germline testing, which is expected to grow exponentially.
To critically review the existing evidence on immune checkpoint inhibitors (ICIs) in early-stage and metastatic breast cancer and discuss emerging strategies in the different breast cancer subtypes.
Immunotherapy has become one of the major milestones in contemporary oncology, revolutionizing the treatment of multiple solid tumors. ICI agents combined with chemotherapy have demonstrated significant efficacy in both early-stage and metastatic triple-negative breast cancer. However, only a subgroup of patients responds to those agents and some associated toxicities, although infrequent, can be life-disabling. Emerging data from immunotherapy studies in advanced hormone receptor-positive (HR +) breast cancer as well as HER2-positive disease are arising with mixed results. Although breast cancer has not classically been considered a hot tumor, ICIs have proven to be effective in a subset of breast cancer patients. However, much remains to be learned, and the identification of new biomarkers beyond PD-L1 expreof ICI but also to identify patients who can avoid them, together with their toxicities and costs.
Restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis has been associated with multiple short- and long-term complications. In this review, we examine the role of biomarkers, imaging, and pouchoscopy in the assessment of patients after ileal pouch-anal anastomosis, with a particular focus on the emergence of novel biomarkers and techniques for evaluating and risk stratifying patients after this procedure in the hopes of improving outcomes in this specific population.
There are indications that that the incidence of pouchitis may be increasing in recent decades. Calprotectin and other non-invasive imaging tests such as ultrasound may offer advantages in distinguishing patients with inflammatory conditions of the pouch from other etiologies. In the search for other biomarkers that may identify patients at risk for inflammatory conditions of the pouch, the stool microbiota and metabolomics may play a key role in identifying those patients at greatest risk for complications. Advances in biomarkers, imaging, and standardized pouchoscopy scoring offer immediate improvements in clinical care and will prompt future research efforts.
There are indications that that the incidence of pouchitis may be increasing in recent decades. Calprotectin and other non-invasive imaging tests such as ultrasound may offer advantages in distinguishing patients with inflammatory conditions of the pouch from other etiologies. In the search for other biomarkers that may identify patients at risk for inflammatory conditions of the pouch, the stool microbiota and metabolomics may play a key role in identifying those patients at greatest risk for complications. Advances in biomarkers, imaging, and standardized pouchoscopy scoring offer immediate improvements in clinical care and will prompt future research efforts.The basic performance of photon-counting detector computed tomography (PCD CT) is superior to conventional CT (energy-integrating detector CT EID CT) because its spatial- and contrast resolution of soft tissues is higher, and artifacts are reduced. Because the X-ray photon energy separation is better with PCD CT than conventional EID-based dual-energy CT, it has the potential to improve virtual monochromatic- and virtual non-contrast images, material decomposition including quantification of the iodine distribution, and K-edge imaging. Therefore, its clinical applicability may be increased. Although the image quality of PCD CT scans is superior to that of EID CT currently, further improvement may be possible. The introduction of iterative image reconstruction and reconstruction with deep convolutional neural networks will be useful.
To investigate the potential of histogram analysis based on diffusion kurtosis imaging (DKI) in evaluating renal function and fibrosis associated with chronic kidney disease (CKD).
Thirty-six CKD patients were enrolled, and DKI was performed in all patients before the renal biopsy. The histogram parameters of diffusivity (D) and kurtosis (K) were obtained using FireVoxel. The histogram parameters between the stable [estimated glomerular filtration rate (eGFR) ≥ 60ml/min/1.73 m
] and impaired (eGFR < 60ml/min/1.73 m
) eGFR group were compared. Besides, patients were classified into mild, moderate, and severe fibrosis group using a semi-quantitative standard. The correlations of histogram parameters with eGFR and fibrosis scores were investigated and the diagnostic performances of histogram parameters in assessing renal dysfunction and fibrosis were analyzed. The added value of combination of most significant parameter with 24 h urinary protein (24 h-UPRO) in evaluating fibrosis was also explored.
Secable for the noninvasive assessment of renal function and fibrosis in CKD patients.
Histogram analysis based on DKI is practicable for the noninvasive assessment of renal function and fibrosis in CKD patients.
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