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
Background: Before implementation of the new scale, the Swedish modified version of the Postural Assessment Scale for Stroke Patients (SwePASS), to clinical practice, it is fundamental to analyze its measurement properties.Objective: To examine the inter-rater reliability of the SwePASS in the acute phase after stroke.
Methods: Day 3 to day 7 after admission to a stroke unit, 64 persons with stroke were assessed twice, using the SwePASS, by two physiotherapists. Inter-rater reliability was determined using percentage-agreement and the rank-invariant method: relative position, relative concentration, and relative rank variance.
Results: The raters showed a percentage agreement of ≥75% in the assessments using the SwePASS. For 9 of the 12 items, the percentage agreement was >80%. For 8 of the 12 items, there was a statistically significant change in position, revealed in relative position values between 0.08 and 0.15. Three items had statistically significant positive relative concentration values between ?0.11 and 0.10. Except for a statistically significant negligible relative variance value of 0.01 for the items 1 and 8, there was no relative variance.
Conclusions: The SwePASS shows an acceptable inter-rater reliability, albeit with potential for improvement. The reliability can be improved by a consensus how to interpret the scale between the raters prior to implementation in the clinic. 相似文献
AbstractThis study was undertaken to compare the concentrations of pro- and anti-angiogenic growth factors, nitric oxide (NO) stable metabolites in maternal serum and embryonic left ventricular (LV) isovolumic relaxation time (IRT, ms) during the first trimester in two groups of women: with pregnancy conceived by assisted reproductive technologies (ART, n?=?39) and normally conceived (control group, n?=?68) pregnancy. The concentration of vasoconstrictor endothelin 1 was 45.5 times more in ART than in control group. On the contrary, the concentrations of NO stable metabolites in ART were 1.9 times less than in control women. The assessment of angiogenic suppressors in ART women demonstrates the decrease in s-endoglin concentration was 1.6 times and in soluble receptor to vascular endothelial growth factor concentration was 2.0 times in comparison with control group. There was a significant increase in LV IRT in ART embryos in comparison to control ones. These data suggest significant changes in pro- anti-angiogenic factors balance and increase in vascular impedance in ART-conceived embryos. 相似文献
Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4+ and CD8+ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity. 相似文献
The objective of this review is to identify and review publications describing the impact of reduced somatosensation on balance. Based on knowledge of the association between specific somatosensory loss and deterioration of balance, conclusions can be made about role of somatosensation in standing balance.A systematic literature review is presented in which publications from the years 1993 through 2007 were searched in Medline and Embase. Medical Subject Headings (MESH) terms and free text words (related to balance, somatosensory loss, and lower limb) were used to perform the searches. Fifteen articles were selected for detailed review based on predetermined inclusion criteria, and three of the included articles described the effect of experimentally reduced somatosensation on balance in healthy subjects. Ten of the articles described balance in diabetic neuropathy (DN). The last two included articles described balance in Charcot-Marie-Tooth (CMT) disease type 1A (CMT1A) or type 2 (CMT2).The literature indicates that the tactile sensation is reduced in DN, CMT1A, and CMT2 and when the plantar surface of the feet was hypothermically anesthetized. Joint motion sensation seems to be impaired in patients with DN, and passive joint position sensation appears to be reduced in healthy subjects with anesthesia of ankle and foot from prolonged ischemia. This reduced somatosensation seems to have a negative effect on balance in patients with DN and CMT2; however, this appeared not to be the case in patients with CMT1A and in healthy subjects. 相似文献
Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone. 相似文献
Massive immune hemolysis due to passenger lymphocyte-derived anti-D has not been reported in renal transplantation. A 50-year-old (B-positive) male received a dual deceased-donor kidney transplant (B-negative) for diabetic renal failure. Two weeks post-transplant, the patient developed severe hemolytic anemia. The donor anti-D titer was 1:8. The recipient anti-D titer (zero pre-transplant) increased from 1:4 to 1:16 over 4 days. Rapid hemolysis caused severe anemia, minimum Hb = 4.2 g/dL, while selectively lysing the patient's autologous red cells during this time. The hemolytic anemia did not impair the allografts and subsided without monoclonal B-cell pharmacotherapy or apheresis. The anti-D titer decreased to barely detectable levels at four months and had cleared when checked 2 years post-transplant. Transfusion support subsided after two months. If complications of anemia can be avoided, the deleterious effects of hemolysis may be well tolerated by renal allografts using antigen negative transfusion alone. 相似文献