Management of dermatological adverse events during nivolumab treatment

Programmed death 1 receptor (PD-1) inhibitors, such as nivolumab, are effective in the treatment of advanced and metastatic melanoma, as well as in kidney, bladder, and non-small cell lung carcinomas. Adverse events of PD-1 inhibitors result mostly from autoimmune mechanisms, include gastrointestinal inflammatory diseases, hepatotoxicity, neurotoxicity, endocrinopathies, and skin toxicities. In this article, we highlight the main cutaneous adverse events associated with PD-1 inhibitors and provide a set of practical guidelines about their management. Additionally, we report a case of nivolumab-induced bullous pemphigoid in a patient with metastatic melanoma.Programmed death 1 receptor (PD-1) inhibitors, such as nivolumab, are effective in the treatment of advanced and metastatic melanoma, as well as in kidney, bladder, and non-small cell lung carcinomas. Adverse events of PD-1 inhibitors result mostly from autoimmune mechanisms, include gastrointestinal inflammatory diseases, hepatotoxicity, neurotoxicity, endocrinopathies, and skin toxicities. In this article, we highlight the main cutaneous adverse events associated with PD-1 inhibitors and provide a set of practical guidelines about their management. Additionally, we report a case of nivolumab-induced bullous pemphigoid in a patient with metastatic melanoma

Postępowanie w przypadku wystąpienia dermatologicznych działań niepożądanych przy stosowaniu leku niwolumab

Zastosowanie leków z grupy inhibitorów punktu kontrolnego PD-1 okazało się postępem w leczeniu chorych na zaawansowanego czerniaka. Udowodniono ich skuteczność również w leczeniu innych nowotworów, takich jak rak nerki, pęcherza moczowego czy niedrobnokomórkowy rak płuca. Działania niepożądane inhibitorów PD-1, wynikające przede wszystkim z mechanizmów immunologicznych, obejmują szerokie spektrum zaburzeń, w tym zaburzenia gastroenterologiczne, hepatotoksyczność, neurotoksyczność, endokrynopatie oraz szereg reakcji skórnych. W niniejszym opracowaniu zostaną omówione najczęstsze dermatologiczne działania niepożądane niwolumabu oraz zasady postępowania w przypadku ich wystąpienia. Ponadto przedstawiony zostanie przypadek pacjentki leczonej niwolumabem z powodu czerniaka, u której wystąpił pemfigoid pęcherzowy wywołany zastosowaniem leku

Quasimonoenergetic electron beams with relativistic energies and ultrashort duration from laser-solid interactions at 0.5 kHz

International audienceWe investigate the production of electron beams from the interaction of relativistically-intense laser pulses with a solid-density SiO2 target in a regime where the laser pulse energy is -mJ and the repetition rate -kHz. The electron beam spatial distribution and spectrum were investigated as a function of the plasma scale length, which was varied by deliberately introducing a moderate-intensity prepulse. At the optimum scale length of λ/2, the electrons are emitted in a collimated beam having a quasimonoenergetic distribution that peaked at -0.8MeV. A highly reproducible structure in the spatial distribution exhibits an evacuation of electrons along the laser specular direction and suggests that the electron beam duration is comparable to that of the laser pulse. Particle-in-cell simulations which are in good agreement with the experimental results offer insights on the acceleration mechanism by the laser field. © 2009 The American Physical Society

Effects of Osthole on Inflammatory Gene Expression and Cytokine Secretion in Histamine-Induced Inflammation in the Caco-2 Cell Line

Hyperactivity of the immune system in the gastrointestinal tract leads to the development of chronic, inflammation-associated disorders. Such diseases, including inflammatory bowel disease, are not completely curable, but the specific line of treatment may reduce its symptoms. However, the response to treatment varies among patients, creating a necessity to uncover the pathophysiological basis of immune-mediated diseases and apply novel therapeutic strategies. The present study describes the anti-inflammatory properties of osthole during histamine-induced inflammation in the intestinal Caco-2 cell line. Osthole reduced the secretion of cytokines (CKs) and the expression level of inflammation-associated genes, which were increased after a histamine treatment. We have shown that the secretion of pro-inflammatory CKs (IL-1β, IL-6, IL-8, and TNF-α) during inflammation may be mediated by NFκB, and, after osthole treatment, this signaling pathway was disrupted. Our results suggest a possible role for osthole in the protection against inflammation in the gastrointestinal tract; thus, osthole may be considered as an anti-inflammatory modulator

Vitamin D receptor (VDR) gene polymorphism in patients diagnosed with colorectal cancer

Colorectal cancer (CRC) is one of the most commonly occurring neoplasias in humans. The prevalence of CRC rates is still rising. Although the exact background of the disease still remains unknown, it is believed that CRC may not only be a result of environmental factors, but also genetic ones. One of the mechanisms underlying CRC might be the vitamin D pathway, as CRC is the most closely linked neoplasia to vitamin D deficiency. This study shows a possible association of the vitamin D receptor (VDR) polymorphisms FokI, BsmI, ApaI, and TaqI with CRC susceptibility. A total of 103 patients diagnosed with CRC (61 men and 42 women, aged 57–82 years) and 109 healthy people (50 men and 59 women, aged 47–68 years) were genotyped using PCR-RFLP for FokI, BsmI, ApaI, and TaqI. None of the single nucleotide polymorphisms (SNPs) individually increased or decreased the risk of CRC. The evaluation of haplotypes revealed two that might enhance the likelihood of CRC development: taB (OR = 30.22; 95% CI 2.81–325.31; p = 0.01) and tAb (OR = 3.84; 95% CI 1.29–11.38; p = 0.01). In conclusion, genotyping is an easy and robust procedure that needs to be performed only once in a lifetime. A creation of a relevant SNP’s panel might contribute to the identification of the groups that are at the greatest risk of CRC.</p

Vitamin D binding protein (VDBP) and its gene polymorphisms—the risk of malignant tumors and other diseases

Vitamin D is an important component of the endocrine system that controls calcium homeostasis and bone mineralization. Because of the very short half‐life of free serum vitamin D it is stabilized and transported to target tissues by being bound to the vitamin D binding protein (VDBP). The most common polymorphisms: rs4588 and rs7041 in the vitamin D binding protein gene may correlate with differences in vitamin D status in the serum. This review presents data that relate to the presence of genetic variants in the VDBP gene in correlation with certain diseases, mostly concerning cancers (breast, prostate, pancreatic, lung, colorectal, basal cell carcinoma cancer and cutaneous melanoma) or other related diseases (thyroid autoimmunity disorders, obesity, diabetes mellitus, bone metabolism, rheumatoid arthritis, ankylosing spondylitis, asthma, chronic obstructive pulmonary disease, tuberculosis and coronary artery diseases)

Vitamin D Metabolic Pathway Components in Orthopedic Patientes—Systematic Review

Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring proper bone growth and functioning, and its deficiencies are indicated in various diseases, mainly in the proper structure and function of the skeleton. In this review, we focus on the most important components of the vitamin D metabolic pathway, in correlation with selected orthopedic conditions. Records were obtained from the PubMed database in a timeline of 2010–2022. The keywords were as follows: vitamin D/cholesterol/vitamin D binding protein/ VDBP/Cytochrome/CYP24A1/CYP 27B1/Vitamin D receptor/VDR/ + diseases (ACL reconstruction, rotator cuff, arthroplasty knee/hip/shoulder). The recent original studies were analyzed, discussed, and the most important data were shown. The vast majority of articles concern the metabolite of vitamin D (25(OH)D), which is measured as a standard in diagnostic laboratories. Even though there is a lot of valuable information in the literature, we believe that the other elements of the vitamin D pathway also deserve attention and suggest their research in correlation with orthopedic disorders to supplement the missing knowledge on this topic