Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.
Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.
Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices. 相似文献
This study is focussed on micro-encapsulation of essential oils in polylactic acid (PLA) and a poly(methyl methacrylate) (PMMA) matrix as well as blends of the same. Microspheres were prepared by the solvent evaporation technique and characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infra-red spectroscopy (FTIR). The encapsulation efficiencies and release profiles of the essential oils were studied by gas chromatography mass spectrometry (GC-MS) and head-space solid-phase microextraction GC-MS, respectively. Furthermore, the microspheres were tested for antibacterial activity against both Gram-negative and Gram-positive bacterial strains.
The results showed that the microspheres compositions (PLA/PMMA ratio) have significant effect on their characteristics. The process adopted for preparing the microspheres promoted formation of spherical particles at the sizes of 1.5–9.5?µm. The highest encapsulation efficiency of the prepared microspheres was observed in systems consisting of linalool (81.10?±?10.0?wt. % for PLA system and 76.0?±?3.3?wt. % for PMMA system). Confirmation was also made that the release rate of the microspheres was affected by the size of the same. 相似文献
PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%. 相似文献
ObjectiveIdentifying biomarkers for abdominal aortic aneurysms (AAA) could prove beneficial in prognosis of AAA and thus the selection for treatment. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein that is highly expressed in aorta. MFAP4 is involved in several tissue remodeling-related diseases. We aimed to investigate the potential role of plasma MFAP4 (pMFAP4) as a biomarker of AAA.MethodsPlasma samples and data were obtained for 504 male AAA patients and 188 controls in the Viborg Vascular (VIVA) screening trial. The pMFAP4 levels were measured by Alphalisa. The Mann-Whitney U test assessed differences in pMFAP4 levels between the presence and absence of different exposures of interest. The correlation between pMFAP4 and aorta growth rate were investigated through spearman's correlation analysis. Immunohistochemistry and multiple logistic regression adjusted for potential confounders assessed the association between pMFAP4 and AAA. Multiple linear regression assessed the correlation between pMFAP4 and aorta growth rate. Cox regression and competing risk regression were used to investigate the correlation between AAA patients with upper tertile pMFAP4 and the risk of undergoing later surgical repair.ResultsA significant negative correlation between pMFAP4 and aorta growth rate was observed using spearman's correlation analysis (ρ = −0.14; P = .0074). However, this finding did not reach significance when applying multiple linear regression. A tendency of decreased pMFAP4 was observed in AAA using immunohistochemistry. Competing risk regression adjusted for potential confounders indicated that patients with upper tertile pMFAP4 had a hazard ratio of 0.51 (P = .001) for risk of undergoing later surgical repair.ConclusionsHigh levels of pMFAP4 are associated with a decreased likelihood of receiving surgical repair in AAA. This observation warrants confirmation in an independent cohort. 相似文献
Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase. 相似文献