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COVID-19 infection has been a global health issue in the past recent years and numerous topics are studied in order to discover its pathophysiology and potential side effects. The potential for disease recurrence following the administration of the COVID-19 vaccine is one of the issues that has recently attracted attention. Several studies have revealed that the COVID-19 vaccines, like other vaccines, may have side effects and, in some cases, they may even deteriorate the underlying illnesses, such as rheumatic diseases, autoimmune diseases, and cancers. The effectiveness and safety of the COVID-19 vaccine for patients with malignancies are one of the factors that are considered regarding this vaccine. Lymph node involvement, disease recurrence, and potential paraclinical changes after receiving the COVID-19 vaccine are some of the concerns of patients with malignancy. In this mini-review, we attempted to investigate cases of cancer recurrence or recovery as well as lymphadenopathy following vaccination.

Leber’s hereditary optic neuropathy (LHON) is a fairly prevalent mitochondrial disorder (1:50,000) arising from the dysfunction of the mitochondrial respiratory chain, which eventually leads to apoptosis of retinal ganglion cells. The usual presentation is that of a young male with a sequential reduction in visual acuity. OCT has been used to study the pattern of optic nerve involvement in LHON, showing early thickening of the inferior and superior retinal nerve fibre layer and ganglion cell layer thinning corresponding with the onset of symptoms. Of the three primary mutations for LHON, the m.14484T>C mutation has the best visual prognosis. Recent emerging therapeutic options for LHON include idebenone and the introduction of genetic vector therapy, which is currently in phase III clinical trials. Screening of family members and adequate advice to avoid environmental triggers, such as smoking and alcohol consumption, are also cornerstones in the management of LHON.

Malignant melanoma (MM) of mucosal membranes (excluding anus and head-neck) is a rare but aggressive disease with poor outcomes. The knowledge of this tumor's development, etiology, and management is scarce, mainly due to the low case numbers. We presented eight cases and performed a comprehensive literature review on mucosal MM (between 1970 and 2020). We identified 47 manuscripts on 55 patients with primary mucosal MM (limited to urothelium and vagina) and reviewed demographics, tumor specifications (morphology, stage, etc.), management, and survival. We identified 10 manuscripts discussing treatment in 1595 mucosal and non-mucosal MM and extracted the data regarding the non-surgical treatment modalities of mucosal MM patients. In 63 cases, 48 tumors primarily occurred in the urothelium (urethra: 47, bladder: 1) and 15 in the vagina. Molecular studies in a subset of cases revealed alterations in c-KIT, NRAS, BRAF (non-V600E and V600E), TP53, and NF1. Fifty-three patients underwent surgery (with additional chemotherapy, immunotherapy, and radiotherapy in 19, eight, and eight patients, respectively). The outcome was available in 52 cases, showing 21 deaths, 10 without recurrence, two alive with disease, and five lost to follow-up. Shared genetic signatures in mucosal and skin MM suggest a similar development mechanism; however, unlike skin MM, there are less BRAF mutations and more PI3K/AKT/mTOR pathway alterations in mucosal MM. Prolonged chemotherapy (i.e., methotrexate) and immune-modulating agents (i.e., natalizumab) may be risk factors. The stage at diagnosis and proper surgical extirpation are keys to the prognosis and survival of patients.

We sought to investigate the influence of SARS-CoV-2 infection on the cytokine profiles of peripheral blood mononuclear cells (PBMCs) and neutrophils from coronavirus disease 2019 (COVID-19) intensive care unit (ICU) patients. Neutrophils and PBMCs were separated and stimulated with the mitogen phytohemagglutinin. Culture supernatants of mitogen-stimulated PBMCs and neutrophils from 88 COVID-19 ICU patients and 88 healthy controls were evaluated for levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α, IFN-γ, interleukin (IL)-2, -4, -5, -6, -9, -10, -12, -17A, and tumor necrosis factor (TNF)-α using anti-cytokine antibody MACSPlex capture beads. Cytokine profiles of PBMCs showed significantly lower levels of GM-CSF, IFN-γ, IL-6, IL-9, IL-10, IL-17A, and TNF-α (p < 0.0001) in COVID-19 ICU patients. In contrast, COVID-19 ICU patients showed higher median levels of IL-2 (p < 0.001) and IL-5 (p < 0.01) by PBMCs. As for neutrophils, COVID-19 ICU patients showed significantly lower levels of GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-17A, IL-12, TNF-α (p < 0.0001), and IFN-α (p < 0.01). T-helper (Th)1:Th2 cytokine ratios revealed lower inflammatory cytokine for PBMCs and neutrophils in COVID-19 ICU patients. Cytokine production profiles and Th1:Th2 cytokine ratios suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has an immunomodulatory effect on PBMCs and neutrophils. This study also suggests that the increased levels of several cytokines in the serum are not sourced from PBMCs and neutrophils.

e14547 Background: Eighty percent of nonmelanoma skin malignancies are basal cell carcinomas (BCC). Metastasis in BCC is about 0.0028 to 0.55. Diagnosis and treatment of metastatic BCC is challenging due to its rarity. In approximately 85% of metastatic BCC, the most common metastatic organs are lymph nodes. Methods: We reviewed 31 skin BCCs with bone metastasis in the past 60 years and 10 observation studies on the efficacy of Sonic hedgehog inhibitors (SHHis). We focused on treatment and outcome of 31 metastatic BCC. Results: The main treatment option was surgery and radiotherapy is a palliative option. Among chemotherapeutic and immunotherapeutic agents, SHHis (e.g. vismodegib and sonidegib) appear to be effective, with reported ORR of 43-100%, and CRR range of 3%-54%. In locally advanced BCCs, vismodegib shows 10 times higher CRRs compared to sonidegib, although ORRs were similar. In metastatic BCC, overall response to vismodegib was three times higher. The common adverse effects of SHHis limit their administration. Conclusions: BCC is a common skin neoplasm that rarely demonstrates metastasis. Among the chemotherapy agents administered, vismodegib appears promising.[Table: see text]

e21506 Background: Malignant melanoma (MM) of mucosal membranes (excluding anus and head and neck) is a rare but aggressive disease with poor outcome. There is little information available on the mechanism of development, risk factors and management of this tumor, mainly due to the low number of cases. Methods: We performed a literature review on MMM (between 1970-2020) with a focus on nonsurgical management and outcome. Results: We identified 9-papers discussing 1500-MM cases. Formerly, for the management of MMM, Dacarbazine, Interferon b, DAV-Feron, Carboplatin, Imatinib, and Paclitaxel were administered. More recently, novel immunotherapeutic and chemotherapeutic medications such as Immune Checkpoint Inhibitors (ICPI) and anti-VEGF agents have been administered in these patients. In 502 patients of metastatic MMM, adding ipilimumab to dacarbazine increased OS from 9.1-to-11.2 months with one year survival increasing from 36.3%-to-47.3 %. For nivolumab & ipilimumab combination therapy in 361 patients with MMM and CMM, MPSF in nivolumab monotherapy was 3-months and 6.2-months (for MMM and CMM, respectively); but in nivo-ipili combination, MPFS was 5.9-months and 11.7-months (for MMM and CMM, respectively). A benefit of bevacizumab addition to platinum-based chemotherapy in patients showing advanced disease on ICPI is unknown; however, combination-therapy may be reasonable if no access to ICPI or autoimmune diseases. Conclusions: MMM patients could benefit from combination of nivolumab to ipilimumab more than monotherapy with either medication alone.[Table: see text]

2525 Background: Immune checkpoint inhibitors (ICIs) can cause a variety of inflammatory autoimmune tissue damage, referred to as immune-related adverse events (irAEs). COVID-19 is associated with increased amounts of proinflammatory cytokines, which may synergistically affect the outcome of irAEs. Data are limited regarding the impact of COVID-19 on irAEs in ICI-treated cancer patients. Methods: We retrospectively analyzed adult patients with malignant solid tumors treated with ICIs at AdventHealth Orlando between August 2020 and August 2021. All COVID-19 infections were confirmed by PCR. Patients who had the most recent ICI treatment over one month before or after the positive COVID-19 test were excluded from the study. For COVID-19 positive group, only the irAEs that developed after COVID-19 infection were considered as events. Results: A total of 579 patients were included in our study, with 46 (7.9%) in COVID-19 positive group, and 533 (92.1%) in COVID-19 negative group. The baseline characteristics of patients in the two groups were similar in terms of age, ethnicity, ECOG, cancer histology, and type of ICI. With a median follow-up of 10 months (1-73 months), no differences in the time from ICI initiation to irAE onset, corticosteroid use, or additional immunosuppressant use were seen. A trend in higher incidence of all-grade diarrhea/colitis (8.7% vs. 3.0%, p=0.07) and grade 3 and 4 hepatitis (4.3% vs. 0.8%, p=0.08) was noted in the COVID-19 positive group, however the difference was not statistically significant. No significant difference in the incidence of pneumonitis (2.2% vs. 1.1%, p=0.44), nephritis (2.2% vs. 0.8%, p=0.34) or dermatitis (6.5% vs. 6.4%, p=1.00) were noted between COVID-19 positive and negative groups. We noticed a higher incidence of all-grade irAEs in the COVID-19 positive group (30.4% vs. 19.9%, p=0.18), but the difference was not statistically significant. The incidence of grade 3 and 4 irAEs was significantly higher in the COVID-19 positive group (10.9% vs. 3.2%, p=0.02). Nine COVID-19 related death occurred while no irAE-related death was noted in the entire cohort. Conclusions: Our study suggested that COVID-19 may pose a risk of severe irAEs in cancer patients receiving ICIs. Close monitoring and possible delaying ICI administration could be considered when cancer patients were infected with COVID-19. [Table: see text]

To examine the role of the transcription factor nuclear factor-erythroid 2 (NF-E2)–related factor 2 (Nrf2) and the SAFE pathway (JAK/STAT) in the induction of germ cell apoptosis (GCA) and the protective role of epigallocatechin-3-gallate (EGCG) during testicular ischemia reperfusion injury (tIRI). Male Sprague-Dawley rats (n = 18) were divided into three groups: sham, unilateral tIRI, tIRI + epigallocatechin-3-gallate (EGCG, 50 mg/Kg). Unilateral tIRI was induced by 1-h ischemia followed by 4-h reperfusion, and EGCG was injected i.p. 30-min post ischemia. Immuno-histological analyses were used to detect spermatogenesis, oxidative DNA damage, and the immuno-expression of the JAK2, STAT3, and STAT1. Biochemical assays were used to investigate the oxidative, apoptosis proteins and enzymes, while Western blot was used to detect the expression of NOX and Nrf2. Expression of apoptosis-related genes was measured by real-time PCR. During tIRI, there was a clear damage to spermatogenesis associated with decreased activities of SOD, CAT, and GPx and increased levels of lipid peroxidation and oxidative DNA damage. In addition, GCA was indicated by the activation of caspase1, PARP, decreased gene expression of survivin and increased Bax to Bcl2 ratio. In contrast to lowered Nrf2 levels, NOX levels were augmented and phosphorylation of JAK2, STAT3, and STAT1 was increased. Pre-perfusion treatment with EGCG prevented the above modulations. The coordinated activation of the SAFE pathway and suppression of Nrf2 contribute to the tIRI-induced oxidative damages and GCA, which were modulated by EGCG.