Ototoxicity in Immune Checkpoint Inhibitors Therapy.

<b><br>Introduction:</b> Immune checkpoint inhibitors (ICIs) and T-cell therapies are a modern, well-established cancer treatment. The priority of oncological treatment is to cure cancer. However, treatment-related toxicities, i.e. immune-related adverse events (irAEs), continue to emerge and are not that well understood yet. ICIs can cause profound, multiple, and diverse irAEs - the sequelae of unknown mechanisms. One of the organs susceptible to collateral damage is the hearing organ. Complications related to hearing, tinnitus, and balance disorders are extremely burdensome and significantly impair many aspects of the quality of life of patients and survivors.</br> <b><br>Aim:</b> The aim of the work is to review the literature in the area of ototoxicity of ICIs.</br> <b><br>Materials and method:</b> A systematic search of the Web of Science, PubMed, and Embase databases for studies published until 1 March 2022 was conducted.</br> <b><br>Results:</b> Reported clinical symptoms ranged from sudden bilateral hearing loss and imbalance to mild hearing loss or tinnitus with preserved hearing. It was found that the median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss in the majority of patients (>60%), and at least one other irAE accompanied the hearing loss in 2/3 of patients. Hearing loss significantly improved in 45.7% of the patients.</br> <b><br>Conclusions:</b> The majority of cases of ICI-related hearing loss presented in the literature were reversible. Therefore, it is important to develop and implement routine therapeutic algorithms. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnostics, and management.</br>.

Time-dependent observations of secretion marker levels in nasal secretion after histamine and methacholine provocations.

Nasal provocation tests with histamine and methacholine were carried out on 25 healthy men in an effort to assess the dynamic changes of albumin, total IgA, secretory IgA and lactoferrin concentrations in the nasal secretion. The trials were performed with 0.5, 1, and 4 mg of histamine and 8, 16, and 32 mg of methacholine. Each dose of histamine or methacholine was sprayed into the nose every 2nd day, with two days' interval between the two provoking agents. Nasal secretions were collected after saline spraying only, forming the baseline group, after 3, 10 and 15 min of administration of the challenge agent. The baseline levels presented the following values: for albumin 257 +/- 230 microg/ml, secretory IgA 608 +/- 379 microg/ml, total IgA 1025 +/- 423 micog/ml, and lactoferrin 213 +/- 156 microg/ml. The increase in albumin level after nasal provocation, particularly significant after histamine administration (to 3713 +/- 2311 microg/ml), indicates incessant protein plasma leakage from the blood circulation to the nasal secretion. After administration of both provocating agents, there was a significant gradual decrease in secretory IgA level, even below the baseline value. After the 2nd and 3rd doses of methacholine and histamine spray, the concentration of secretory IgA decreased by 2-3 times and was found to be 200-300 microg/ml, respectively. Also, lactoferrin concentration values decreased gradually after the 2nd and 3rd doses of methacholine and histamine to levels close the baseline value. These observations suggest a time- and dose-dependent, non-specific dysfunction of local immunity response after nasal provocations.