Cutaneous manifestations induced by check point inhibitors in 120 melanoma patients-The European MelSkinTox study.

BACKGROUND: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation. METHODS: We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into four categories: inflammatory dermatosis, bullous diseases, drug-related eruptions and pigmentary diseases. RESULTS: Inflammatory benign dermatoses (n = 63) represented the most common group of reactions (52.5%), followed by drug-related eruptions (n = 24, 20%), pigmentary diseases (n = 23, 19.2%) and bullous diseases (n = 10, 8.3%). Grade II (n = 41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculopapular rash, pruritus, psoriasis-like rash, urticarial eruption and vitiligo. Grade III (n = 18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption and rashes. Grade IV (n = 2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n = 95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time-to-onset of 208 days and some late-onset events. CONCLUSION: Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I-II cutaneous IrAE are easily managed allowing ongoing anticancer treatment. Severe late-onset cutaneous irAE are not uncommon. A dermatological follow-up helps mitigate the risk of life-threatening adverse events. These findings highlight the importance of oncodermatological involvement in management of patients with melanoma receiving immunotherapy.

Urinary neopterin and kynurenine in patients submitted to surgical stress with different inhalational anesthetics (halothane or isoflurane).

Measurements were taken of urinary levels of neopterin (NPT) and kynurenine (KYN), using an HPLC method for their simultaneous analysis in patients submitted to anesthetical surgical stress with two different inhalational anesthetics (halothane and isoflurane). We studied twenty-one women affected by uterine fibromyomatosis and submitted to total hysterectomy (mean age of 42.7+/-5.4 years). They showed the same pre-operative evaluation (ASA-1), and underwent the same i.v. anesthetic treatment. Our patients were randomized in two groups: Group A: 11 patients had halothane as an inhalational anesthetic drug for the maintenance of the anesthetic induction (mean time= 1 h). Group B: 10 patients had isoflurane. A significant decrease in urinary NPT and KYN, parallel to serum-NPT, was found 4 h after anesthetic induction. Raised NPT levels appeared 24 h after A.I. with significant increased levels after 7 days. A strong correlation between urinary and serum NPT levels was seen (Rs= 0.74; p < 0.001). Significantly low KYN levels were observed both 4 h and 24 h after A.I.. In addition to the delayed increase of the excretory KYN levels, significantly raised KYN levels in Group B (isoflurane) 48 h after A.I. (10.59+/-14.31 vs 5.99+/-7.17 micromol/mol creat.; p < 0.01) were shown, whereas in Group A (halothane) we observed a progressive increase as compared to the pre-surgery values starting from 72 h after surgery. Our data seem to show that: (a) it is possible to have a biochemical and non invasive monitoring of the anesthetical-surgical stress on MM "priming" activity; (b) the activation of the phagocyte compartment is one of the earlier immunological events after surgery (NPT), but the efficiency of this "priming" appears to be delayed (KYN); (c) isoflurane appears to induce an earlier recovery in MM activation.

Comparison of seven serum assays on four automatic analysers.

Serum enzyme assays used on four different analysers (Hitachi 737, Hitachi 705, Cobas-bio and RA-2X) were compared by determining the activity of seven different enzymes (AST, ALT, LD, ALP, GGT, CK and AMS). Performance checks (quality control procedure) and replications (the study of the total analytic imprecision and of its components) were conducted and the methods were compared by linear regression analysis with statistical inference on the curves following the protocols of the National Committee for Clinical Laboratory Standards (NCCLS: PSEP- 2, PSEP-3, PSEP-4). The correlation coefficients between the methods (r = 0.991-0.999), together with the other statistical parameters, indicated that the methods are well correlated on all the instruments. The total imprecision was good for all analytes, except ALT. Among the instruments tested, the RA-2X gave more variable results, although the total imprecision was acceptable. There was no relevant carry-over effect. The evaluation of performance claims indicated that the expected error did not substantially affect the results at the level of clinical decisions.