High expression of PD-L1 on conventional dendritic cells in tumour-draining lymph nodes is associated with poor prognosis in oral cancer.

INTRODUCTION: Oral squamous cell carcinoma (OSCC), while common and with a favorable prognosis in early stages, presents a marked reduction in survival rate upon metastasis to lymph nodes. Early detection of lymph node metastasis via biomarkers could enhance the therapeutic strategy for OSCC. Here, we explored dendritic cells (DCs) and cytotoxic T-cells in tumour-draining lymph nodes (TDLNs) as potential biomarkers. METHOD: Dendritic cells and cytotoxic T-cells in 33 lymph nodes were analyzed with multi-parameter flow cytometry in TDLNs, regional non-TDLNs surgically excised from 12 OSCC patients, and compared to 9 lymph nodes from patients with benign conditions. RESULTS: Our results displayed a higher proportion of conventional cDC1s with immunosuppressive features in TDLN. Further, high PD-L1 expression on cDC1 in TDLNs was associated with metastasis and/or recurrent disease risk. Also, elevated levels of memory CD8+ T-cells and terminally exhausted PD-1+TCF-1-CD8+ T-cells were observed in TDLNs and non-TDLNs compared to healthy lymph nodes. CONCLUSIONS: We conclude that TDLNs contain cells that could trigger an anti-tumor adaptive response, as evidenced by activated cDC1s and progenitor-like TCF-1+ T-cells. The detection of high PDL1 expression on cDC1s was indicative of TDLN metastasis and an adverse prognosis, proposing that PD-L1 on dendritic cells in TDLN could serve as a predictive biomarker of OSCC patients with a worse prognosis.

Regulatory B cells producing IL-10 are increased in human tumor draining lymph nodes.

The contribution of different immune cell subsets, especially T cells, in anti-tumor immune response is well established. In contrast to T cells, the anti-tumor contribution of B cells has been scarcely investigated. B-cells are often overlooked, even though they are important players in a fully integrated immune response and constitute a substantial fraction of tumor draining lymph nodes (TDLNs) known also as Sentinel Nodes. In this project, samples including TDLNs, non-TDLNs (nTDLNs) and metastatic lymph nodes from 21 patients with oral squamous cell carcinoma were analyzed by flow cytometry. TDLNs were characterized by a significantly higher proportion of B cells compared with nTDLNs (P = .0127). TDLNs-associated B cells contained high percentages of naïve B cells, in contrary to nTDLNs which contained significantly higher percentages of memory B cells. Patients having metastases in TDLNs showed a significantly higher presence of immunosuppressive B regulatory cells compared with metastasis-free patients (P = .0008). Elevated levels of regulatory B cells in TDLNs were associated with the advancement of the disease. B cells in TDLNs were characterized by significantly higher expression of an immunosuppressive cytokine-IL-10 compared with nTDLNs (P = .0077). Our data indicate that B cells in human TDLNs differ from B cells in nTDLNs and exhibit more naïve and immunosuppressive phenotypes. We identified a high accumulation of regulatory B cells within TDLNs which may be a potential obstacle in achieving response to novel cancer immunotherapies (ICIs) in head and neck cancer.

Acute odynophagia: A new symptom of COVID-19 during the SARS-CoV-2 Omicron variant wave in Sweden.

OBJECTIVE: The objective of this study is to present a novel clinical manifestation of infection with the Omicron variant of the SARS-CoV-2 virus affecting mainly young, vaccinated, and healthy adults. We describe a new group of COVID-19 patients seeking emergency care with symptoms similar to the life-threatening condition epiglottitis. Here, we present a case series and discuss management. METHODS: We performed a retrospective single-center case study of patients diagnosed with COVID-19 who were referred to the Ear, Nose, and Throat Emergency Department (ENT ED) between January 1 and January 23, 2022 with clinical symptoms such as acute odynophagia, severe sore throat, and fever. Ethical approval was obtained from the Swedish Ethical Review Authority (2020-02579). Informed consent was obtained from all patients included in the study. RESULTS: Twenty patients meeting inclusion criteria were identified. Fifteen patients were fully vaccinated against COVID-19. Four patients needed a short hospitalization for their symptoms. The most common diagnoses were COVID-19-associated acute viral laryngotracheitis and/or viral pharyngitis. Six patients presented with signs of secondary bacterial infection and were put on antibiotics. CONCLUSION: Previous variants of SARS-CoV-2 infection affected predominantly the lower respiratory tract and were associated with loss of smell and taste in many patients. The Omicron variant seems to affect predominantly the upper airways and cause acute laryngitis without olfactory dysfunction. In some patients, the clinical manifestation is similar to the symptoms of epiglottitis. In such a case, a prompt examination of the larynx is the gold standard to exclude inflammatory edema in the upper airways. None of the patients described in this study developed epiglottitis. In this study, we discuss the management of acute odynophagia in COVID-19 patients.

The holmium:YAG laser lithotripsy-a non-invasive tool for removal of midsize stones of major salivary glands.

Incorporeal lithotripsy by using holmium:YAG laser has been recently successfully spread and used in the treatment of urolithiasis. Although this method is not as common in salivary gland surgery, it is also recommended for endoscopic treatment of sialolithiasis. In this study, we decided to analyse effectiveness of holmium:YAG laser method among patients with midsize stones as the treatment in this particular population is still not determined and remains in dispute. Thus, the primary aim of the study is a prospective, complex analysis of incorporeal holmium:YAG laser lithotripsy effectiveness and safety in patients suffering from sialolithiasis. The examined group consisted of 32 consecutive patients, 17 female (53%) and 15 male (47%). The average age was 42 (age range 22-70). In our series, sialoendoscopy with intraductal lithotripsy was performed in patients with wide range of stone's diameter (3 to 10 mm). The calculi were removed with foreign body forceps or retrieval basket, after stone fragmentation with holmium:YAG laser. The power of the laser during surgery was set at 2.5 to 3.5 W. One shot energy equalled 0.5-0.7 J with frequency of 5 Hz. The bivariate Pearson Correlation and a point-biserial correlation were used to analyse the data. Total success rate of holmium:YAG laser lithotripsy in this consecutive group was equal to 90% and efficacy in the group with excluded cases when endoscopic approach difficulties were experienced (stone not visible) reached 93%. The long-term follow-up revealed that in 26 patients (84%), complete recovery was achieved. Two patients developed Wharton's duct stenosis and one Stensen's duct orifice stenosis (9.5%), of whom one required reoperation. Two patients eventually underwent total excision of submandibular gland. Sialoendoscopy combined with incorporeal laser-assisted lithotripsy proved to be effective and safe method for treatment of sialothiasis with midsize stones (4-8 mm) in population of clinic. Even taking into account the prevalence of complications associated with holmium:YAG laser, it is still safer alternative compared to open surgery where there is a significant risk of the bleeding, wound infection or injury of the facial nerve.

Laryngeal disorders in people living with HIV.

OBJECTIVES: Several studies have shown that HIV infected individuals are at higher risk compared to the general population of developing non-AIDS defining conditions such as some types of cancer, kidney disease, liver disease and others. In this case-control study, we compared the incidence of laryngeal disorders between a treatment-seeking HIV-positive population and uninfected controls. We aimed to investigate whether there are any laryngeal disorders that are overrepresented in HIV-positive individuals. METHODS: This was a case-control study based on retrospective chart review, comparing the incidence of laryngeal, airway, and swallowing disorders in sixty-nine HIV positive individuals and 4178 HIV negative controls treated between January 1, 2016 and December 31, 2017, at the Johns Hopkins Voice Center. RESULTS: A majority of HIV-infected patients (59.4%) had at least one diagnosis belonging to the Vocal cord pathology category compared to 48.2% of controls (OR 1.57, p = 0.065). Compared to the entire treatment-seeking population, HIV patients were more likely to present with laryngeal cancer (15.9% vs. 3.4% in controls, OR 5.43, p < 0.001) and chronic laryngitis (17.4% vs. 4.2%, OR 4.79, p < 0.001). Fungal and ulcerative laryngitis were also overrepresented in HIV-positive individuals (OR 9.45, p < 0.001 and 6.29, p < 0.001, respectively). None of the diagnoses categorized as functional voice disorders, swallowing, or airway problems showed a significant difference between groups. Laryngeal papillomatosis, which is an HPV-dependent disease, had similar prevalence in both groups. CONCLUSIONS: Treatment-seeking HIV-positive patients presenting to a laryngology clinic suffer significantly more often from laryngeal squamous cell carcinoma as well as chronic, fungal, and ulcerative laryngitis compared to HIV-negative individuals. LEVEL OF EVIDENCE: 4.

CD4+ and CD8+ T cells in sentinel nodes exhibit distinct pattern of PD-1, CD69, and HLA-DR expression compared to tumor tissue in oral squamous cell carcinoma.

Anticancer immunotherapies have revolutionized cancer management, yet the effect of systemic anti-programmed cell death protein 1 (PD-1) treatment is predominantly studied in tumor-infiltrating lymphocytes (TILs). Its impact on PD-1 expressing cells in tumor-draining lymph nodes (TDLNs) is not well understood and yet to be explored. Thus, further research aiming for better understanding of the PD-1 pathway not only in tumor tissue but also in TDLNs is warranted. In this study, we investigated the expression of PD-1, CD69, and HLA-DR on CD4+ and CD8+ T cells by flow cytometry analysis of peripheral blood mononuclear cells (PBMCs), TDLNs, and tumor samples from patients with oral squamous cell carcinoma (OSCC). Our data showed that both helper and cytotoxic T lymphocytes in OSCC tissue were highly activated and expressed high level of PD-1 (over 70% positivity). Lymphocytes in TDLNs and peripheral blood expressed significantly lower levels of PD-1 and other activation markers compared to TILs. Moreover, we demonstrated that a significant fraction of PD-1 negative TILs expressed high levels of human leukocyte antigen - DR isotype and CD69. In contrast, PD-1 negative cells in TDLNs and PBMCs scarcely expressed the aforementioned activation markers. Furthermore, we proved that patients with a high percentage of CD3+ PD-1+ cells in tumor-draining lymph nodes had significantly lower disease-free and overall survival rates (log-rank test P = .0272 and P = .0276, respectively). Taken together, we proved that flow cytometry of lymph nodes in OSCC is feasible and may be used to investigate whether PD-1 levels in TDLNs correspond with survival and potentially with response to anti-PD-1 therapy. Such knowledge may ultimately help guide anti-PD-1 treatment.

Dysphonia and dysphagia as early manifestations of autoimmune inflammatory myopathy.

PURPOSE: While dysphagia is a recognized manifestation of autoimmune inflammatory myopathy, a relationship between myositis and dysphonia or laryngeal pathology is not well-documented. We therefore sought to describe the spectrum of laryngeal disorders present in myositis patients, evaluate whether any specific conditions are overrepresented among these patients compared to a large treatment-seeking population, and examine the clinical course and outcomes of these symptoms. MATERIALS AND METHODS: This was a retrospective chart review, including all patients seen at the Johns Hopkins Voice Center between January 2016 and December 2017. Demographic data, comorbidities, and laryngeal diagnoses were extracted from the electronic medical record. The charts of patients with myositis were reviewed further to ascertain details of their laryngeal symptoms and myositis disease course. Associations between myositis and dysphonia/dysphagia were evaluated using binary regression and multinomial logistic regression models to adjust for age, sex, race, and smoking status. RESULTS: Of 4252 patients, sixteen had myositis. Compared to 4236 controls, these patients had significantly higher odds of presenting with muscular voice disorders (adjusted odds ratio (OR*) = 4.503, p* = 0.005) and dysphagia (OR* = 6.823, p* < 0.001). A majority (64.3%, CI:35.6-93.0%) of myositis patients had laryngeal pathology among the presenting symptoms of their myositis. Across all diagnostic categories, there was a non-significant trend towards better outcomes in patients receiving specific interventions for their laryngeal symptoms. CONCLUSIONS: Muscular voice disorders and dysphagia are significantly overrepresented in myositis patients presenting to a laryngology clinic, and in these patients, both are frequently among the presenting symptoms of myositis.

Appropriateness for SARS-CoV-2 vaccination for otolaryngologist and head and neck surgeons in case of pregnancy, breastfeeding, or childbearing potential: Yo-IFOS and CEORL-HNS joint clinical consensus statement.

PURPOSE: SARS-CoV-2 vaccines are a key step in fighting the pandemic. Nevertheless, their rapid development did not allow for testing among specific population subgroups such as pregnant and breastfeeding women, or elaborating specific guidelines for healthcare personnel working in high infection risk specialties, such as otolaryngology (ORL). This clinical consensus statement (CCS) aims to offer guidance for SARS-CoV-2 vaccination to this high-risk population based on the best evidence available. METHODS: A multidisciplinary international panel of 33 specialists judged statements through a two-round modified Delphi method survey. Statements were designed to encompass the following topics: risk of SARS-Cov-2 infection and use of protective equipment in ORL; SARS-Cov-2 infection and vaccines and respective risks for the mother/child dyad; and counseling for SARS-CoV-2 vaccination in pregnant, breastfeeding, or fertile healthcare workers (PBFHW). All ORL PBFHW were considered as the target audience. RESULTS: Of the 13 statements, 7 reached consensus or strong consensus, 2 reached no consensus, and 2 reached near-consensus. According to the statements with strong consensus otorhinolaryngologists-head and neck surgeons who are pregnant, breastfeeding, or with childbearing potential should have the opportunity to receive SARS-Cov-2 vaccination. Moreover, personal protective equipment (PPE) should still be used even after the vaccination. CONCLUSION: Until prospective evaluations on these topics are available, ORL-HNS must be considered a high infection risk specialty. While the use of PPE remains pivotal, ORL PBFHW should be allowed access to SARS-CoV-2 vaccination provided they receive up-to-date information.

Voice improvement in patients with recurrent respiratory papillomatosis after combined treatment with cidofovir and CO2 laser surgery.

Mechanical debulking of laryngeal papillomas is associated with voice disorders due to impairment of the vocal fold's mucosa. Intraepithelial injection of cidofovir reduces damage to the laryngeal structures and thus improves vocal parameters. The aim of our study was to compare vocal quality before and after cidofovir and CO2 laser treatment by means of objective phoniatric parameters and to obtain evidence concerning voice outcomes. The vocal parameters of 42 patients with RRP were assessed before and after intralesional cidofovir and CO2 laser debulking treatment (Lumenis AcuPulse 40 CO2 laser, wavelength 10.6 µm; Lumenis Ltd., Yokneam, Israel). The laser was used in SuperPulse™ mode with power tailored on the target structures (average 7 W). The depth of tissue penetration was 1 mm with a single burst of energy lasting 0.3 ms. Most of the patients had previously undergone traditional surgery (1-105 procedures); in 7/42, the video stroboscopic examination revealed extensive scar tissue covering the mucosa of the vocal folds, limiting the mucosal wave. The significance level for all calculations was p < 0.05. Statistical analysis was performed using Statistica 10 by StatSoft Polska. The methodology included subjective voice evaluation (GRBAS), videostroboscopy, analysis of the acoustic laryngeal tone (MDVP), spectrographic analysis, and voice handicap index (VHI). The GRBAS scale during spontaneous conversation revealed better phonation results after cidofovir treatment in all 42 patients. Scars were not observed in the presented group. In the MDVP laryngeal tone analysis before surgery parameters defining the amplitude and frequency of laryngeal tone were significantly elevated compared to the state after surgery. After treatment, both jitter and shimmer were reduced in all subjects. Even more pronounced changes were observed in the spectrographic analysis. In all analyzed patients, there was a significant reduction in VHI scores showing improvement in voice self-assessment. A satisfactory improvement in voice quality was observed in all RRP patients treated with cidofovir and CO2 laser.

Clinical practice patterns in laryngeal cancer and introduction of CT lung screening.

OBJECTIVES: After the publication of large clinical trials, in January 2014 The U.S. Preventive Services Task Force (USPSTF) recommended annual lung cancer screening with low-dose CT in a well-defined group of high-risk smokers. A significant proportion of patients with laryngeal cancer (LC) meet the introduced criteria, and we hypothesized that clinical practice would change as a result of these evidence-based guidelines. METHODS: Retrospective chart review of patients diagnosed with LC and treated at Johns Hopkins Hospital who met USPSTF criteria for annual chest screening and were followed for at least 3 consecutive years in the years surrounding the introduction of screening guidelines (January 2010 to December 2017) was performed to identify those who had recommended screening CT chest. RESULTS: A total of 151 patients met the inclusion criteria of the study and were followed for a total of 746 patient-years. 184/332 (55%) patient-years in the pre-guidelines period and 246/414 (59%) in the post-guidelines period included at least one recommended chest imaging (CT or PET-CT; p = 0.27). 248/332 (75%) patient-years in the pre-guidelines period and 314/414 (76%) in the post-guidelines period included any radiological chest imaging (X-ray, CT or PET-CT; p = 0.72). Screening scans were ordered by OHNS (45%), Medical Oncology (31%), Radiation Oncology (8%), and primary care (14%) with 70% of patients missing at least one year of indicated screening. CONCLUSIONS: The implementation of new lung cancer screening guidelines did not change clinical practice in the management of patients with LC and many patients do not receive recommended screening. Further study concerning potential barriers to effective evidence-based screening and coordination of care is warranted.

Outcomes of CO2 laser-assisted posterior cordectomy in bilateral vocal cord paralysis in 132 cases.

The purpose of the study was to assess the role of laser-assisted posterior cordectomy in the management of patients with bilateral vocal cord paralysis. We aimed an analysis of 132 consecutive patients treated by CO2 laser posterior cordectomy, aged 38-91, 31% tracheotomized on admission. Cordectomy was performed under microlaryngoscopy using CO2 laser (Lumenis AcuPulse 40 CO2 laser, wavelength 10.6 µm, Lumenis Ltd., Yokneam, Israel). We looked at the number of laser glottic procedures necessary to achieve decannulation in tracheotomized patients and to achieve respiratory comfort in non-tracheotomized subjects and we evaluated the two groups for differences in patient characteristics. In tracheotomized patients, we also assessed factors affecting the success of decannulation and we evaluated the impact of tracheotomy on patients' lives. Decannulation was performed in 63% of tracheotomized patients. In terms of the number of procedures, 54% (14), 19% (5), and 27% (7) tracheotomized vs. 74% (61), 24% (20), and 2% (2) non-tracheotomized subjects underwent one, two, or three procedures, respectively. In the group of tracheotomized patients who were successfully decannulated, the number of multiple laser-assisted procedures was significantly higher than in the group of non-tracheotomized subjects with respiratory comfort after treatment (p = 0.04). Advanced age (> 66 years), comorbidities (diabetes, gastroesophageal reflux disease (GERD)), multiple thyroid surgeries, and tracheotomy below the cricoid cartilage were found to decrease the likelihood of successful decannulation. Posterior cordectomy is a simple method allowing for airway improvement and decannulation in patients with bilateral vocal cord paralysis. It is less effective in tracheotomized subjects with diabetes or GERD, older than 66 years old, after two or more thyroidectomies.

Allergic sensitization does not influence advancement or survival in oral cancer.

A history of allergies has been said to be associated with a lower risk of head and neck cancer compared to the general population. However, it is not known whether having an allergic sensitization influences the prognosis and advancement of cancer disease. Thus, the aim of the study was to investigate the relationship between allergic sensitization and oral cancer advancement and patient survival. Allergen-specific IgE antibodies were investigated by ImmunoCAP™ Rapid in consecutive 80 patients with oral cancer. ImmunoCAP Rapid system tests a mix of representative inhalant allergens such as birch, timothy grass, mugwort, house dust mite, cat, dog, cockroach, olive (pollen), wall pellitory and mold. Eighty patients met the inclusion criteria for the study. Fifteen patients (19%) had positive ImmunoCAP test. There was no statistically significant difference in primary tumour size (T-stage) between groups (60% in allergy vs 68% in non-allergy had T1-T2 stage and 40% vs 32% T3-T4, respectively, p = 0.570). 27% of patients with allergy had nodal metastases compared with 37% of patients without allergy (p = 0.557). Both groups had comparable short-term survival. In conclusion, allergic sensitization does not seem to influence either the advancement or the short-term survival of patients with oral squamous cell carcinoma.

Sentinel node-assisted neck dissection in advanced oral squamous cell carcinoma-A new protocol for staging and treatment.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is used to improve the staging of and guide treatment in patients with early-stage T1-T2 N0 oral squamous cell carcinoma (OSCC). The role of sentinel nodes (SNs) and the use of SN-technique in advanced OSCC (T3-T4 and/or N+) remain to be evaluated. This study investigates the nodal drainage and the rate of positive SNs (SNs+) in all stages of OSCC. MATERIALS AND METHODS: In total, 85 patients with T1-T4 OSCC diagnosed 2019-2021 were included. We used a prolonged interval between peritumoral injection of radionuclide and SPECT-CT to include all SNs. RESULTS: Patients with advanced OSCC presented a higher proportion of contralateral lymphatic drainage and a higher rate of SN+ compared to patients with early-stage disease. T3-T4 and N+ tumors presented a tendency for a higher rate of contralateral lymphatic drainage compared to T1-T2 and N0 tumors (p = 0.1). The prevalence of positive nodes (SNs+) was higher among patients with advanced disease, T3-T4 versus T1-T2 (p = 0.0398). CONCLUSION: SN-assisted ND enables identification and removal of all SNs + and has the potential for more accurate staging and could possibly give prognostic advantages regarding regional recurrence for all OSCC patients, especially among those with advanced disease. The precise localization of the SNs + also suggests that a more individualized ND approach might be possible in the future even for patients with advanced OSCC.

A Novel Method Using Fine Needle Aspiration from Tumor-Draining Lymph Nodes Could Enable the Discovery of New Prognostic Markers in Patients with Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell cancer (cSCC) is the second most common form of skin cancer, characterized by abnormal, accelerated growth of squamous cells. When caught early, most cSCCs are curable. About 5 percent of the cSCC cases have advanced to such an extent, generally metastatic, that they are far more dangerous, with very poor prognosis and challenging to treat. All efforts to find biomarkers, in blood or in the tumor itself, for early identification of patients with a risk for metastasis have so far failed. The present study describes a novel method that enables the identification of lymphocyte markers in tumor-draining lymph nodes. Six patients with advanced cSCC were analyzed using a combination of a sentinel lymph node biopsy (SLNB) protocol, fine needle aspiration (FNA), and flow cytometry. Immunological results from the sentinel nodes were combined with corresponding data from peripheral blood and unfixed tumor tissues. The result demonstrates a striking difference between the subsets of T-cells from the three compartments. Our interpretation of this first pilot study is that the ability to follow specific immunological markers on lymphocytes in tumor-draining lymph nodes will enable the identification of novel prognostic biomarkers not detectable in material from blood and tumor tissues.

A prolonged innate systemic immune response in COVID-19.

Despite the introduction of vaccines, COVID-19 still affects millions of people worldwide. A better understanding of pathophysiology and the discovery of novel therapies are needed. One of the cells of interest in COVID-19 is the neutrophil. This cell type is being recruited to a site of inflammation as one of the first immune cells. In this project, we investigated a variety of neutrophils phenotypes during COVID-19 by measuring the expression of markers for migration, maturity, activation, gelatinase granules and secondary granules using flow cytometry. We show that neutrophils during COVID-19 exhibit altered phenotypes compared to healthy individuals. The activation level including NETs production and maturity of neutrophils seem to last longer during COVID-19 than expected for innate immunity. Neutrophils as one of the drivers of severe cases of COVID-19 are considered as potential treatment targets. However, for a successful implementation of treatment, there is a need for a better understanding of neutrophil functions and phenotypes in COVID-19. Our study answers some of those questions.

Increased IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19.

Interleukin-26 (IL-26) is released by several immune and structural cells following stimulation of toll-like receptors (TLRs), whereupon it can directly inhibit viral replication and enhance neutrophil chemotaxis. Given these unique properties, IL-26 has emerged as an intriguing mediator of host defense in the lungs. However, the role of IL-26 in COVID-19 has not been thoroughly investigated. Here, we characterized the involvement of IL-26 in the hyperinflammation and tissue damage that occurs in patients with acute COVID-19. We found that IL-26 is markedly increased in blood samples from these patients, and that the concentration of IL-26 correlates with those of the neutrophil-mobilizing cytokines IL-8 and TNFα, respectively. Moreover, the increase in blood IL-26 correlates with enhanced surface expression of the "don't eat me" signal CD47 on blood neutrophils isolated from patients with acute COVID-19. Finally, we found that the blood concentration of IL-26 correlates with that of increased lactate dehydrogenase, an established marker of tissue damage, and decreased mean corpuscular hemoglobin (MCH), a previously verified hematological aberration in COVID-19, both of which are associated with severe disease. Thus, our findings indicate that increased systemic IL-26 associates with markers of hyperinflammation and tissue damage in patients with acute COVID-19, thereby forwarding the kinocidin IL-26 as a potential target for diagnosis, monitoring, and therapy in this deadly disease.

Impact of human immunodeficiency virus status on laryngeal cancer survival and locoregional control.

OBJECTIVES: To compare long-term outcomes of laryngeal cancer (LC) in people living with HIV (PLWH) versus uninfected individuals and determine how clinical and viral factors-such as demographics, cancer stage, HIV viral load, and CD4 nadir-contribute to these outcomes. METHODS: This was a retrospective case-control study of 749 patients seen for LC at a single tertiary care center between 2003 and 2017. Of these, 22 had HIV at the time of LC diagnosis, and they were matched in a 1:4 ratio to uninfected controls based on sex, presence of smoking history, and age at cancer diagnosis. Kaplan-Meier survival curves and Cox proportional hazards models were constructed to identify overall and disease-free survival differences based on HIV status, as well as other clinical and viral factors. RESULTS: Compared to all uninfected individuals, PLWH were diagnosed with LC approximately 6 years younger (p = .013). 1-, 2-, and 5-year overall survival for PLWH were 86.4% (63.4%-95.4%), 77.3% (53.7%-89.9%), and 65.8% (40.8%-82.2%), respectively following LC diagnosis, and HIV was not significantly associated with overall (HR = 3.34 [0.59-18.79]) or disease-free survival (HR = 2.12 [0.71-6.36]). The incidence rate of locoregional recurrence among PLWH was 541 compared to 371 per 10,000 person-years in controls, which were not significantly different (p = .420). Furthermore, among PLWH, peak viral load and CD4 nadir were not associated with overall or disease-free survival. CONCLUSION: While previous work has shown that HIV is associated with elevated risk of LC, survival did not differ significantly between PLWH and uninfected individuals in this study. LEVEL OF EVIDENCE: 3.

Tumour-draining lymph nodes in head and neck cancer are characterized by accumulation of CTLA-4 and PD-1 expressing Treg cells.

INTRODUCTION: High Tregs infiltration within the tumour microenvironment (TME) of various cancers shows a positive correlation with poor prognosis. Despite the fact that tumour draining lymph nodes (TDLNs) are recognized as key organs playing a crucial role in response to immunotherapy and modulating anti-cancer immunity, the distribution of Tregs and their role in TDLNs remain uncertain thus far. The purpose of this project is to investigate the density of Tregs in TDLNs and non-TDLNs and their expression of immune checkpoint molecules - PD-1 and CTLA-4. METHODS: Samples including TDLNs, non-TDLNs and metastatic lymph nodes (LNs) from 23 patients with oral squamous cell carcinoma (OSCC) were analyzed by multicolour flow cytometry with a focus on Tregs population and expression of CTLA-4 and PD-1. RESULTS: TDLNs and metastatic LNs were characterized by a significantly higher infiltration of Tregs defined as CD4+FoxP3+CD25highCD127low cells and significantly higher expression of CTLA-4 and PD-1 on Tregs compared with non-TDLNs. Tregs in TDLNs and metastatic LNs co-expressed CTLA-4 and PD-1 abundantly. High expression of these immune check-point molecules correlated with positive N-stage but not with T-stage. CONCLUSION: TDLNs and metastatic LNs are characterized by a high accumulation of Tregs expressing high levels of CTLA-4 and PD-1. High infiltration of Tregs can be a potential driver of an immunosuppressive milieu in TDLNs that can, in turn, favour cancer progression. High accumulation of Tregs expressing CTLA-4 and PD-1 in TDLNs is associated with lymph node involvement, but not with the size of the primary tumour.

An Incidental Finding of a Double-Lumen Trachea.

The aim of this case report is to present an incidental finding of a firm tracheal septum in a 61-year-old woman. The patient was admitted to the hospital with mild dyspnea and a preliminary diagnosis of a tracheal subglottic stenosis. During microlaryngoscopy, just below the subglottic stenosis, a firm, vertical symphysis (septum), forming a double-lumen trachea was found. There was no record of any previous difficulties with intubation. A computed tomography scan performed after the microlaryngoscopy revealed an airway branch arising from the trachea at the level of thyroid gland and joining its lumen below. The radiological and endoscopic findings in the presented case hardly resemble the conditions described in the literature, as the discovered septum does not have a pseudomembranous nature, nor does it form a tracheal bronchus. Therefore, the finding is thought to be an unusual complication of multiple intubations in the past. This is an extremely rare finding and it is important to share our experience in managing a patient with the aforementioned post-intubation complications.

O objetivo deste relato de caso é apresentar um achado incidental de um septo traqueal numa mulher de 61 anos. A paciente foi internada no hospital com dispneia leve e diagnóstico preliminar de estenose subglótica traqueal. A microlaringoscopia realizada mostrou uma sínfise vertical firme (septo) logo abaixo da estenose subglótica, formando uma traqueia de duplo lúmen. Não houve registo de qualquer dificuldade prévia com a intubação. A tomografia computadorizada realizada após a microlaringoscopia revelou um ramo da via aérea originando-se a partir da traquéia ao nível da glândula tiróide e unindo-se ao seu lúmen em baixo. Os achados radiológicos e endoscópicos do caso apresentado dificilmente se assemelham aos descritos na literatura, pois o septo descoberto não é pseudomembranoso, nem forma um brônquio traqueal. Assim, julga-se que o achado seja uma complicação pouco comum no contexto de múltiplas intubações no passado. Este é um achado extremamente raro pelo que é importante partilhar a nossa experiência no tratamento de um doente com as complicações pós-intubação supra-citadas.