The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma.

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

Prognostic effects of different treatment modalities for hypopharyngeal squamous cell carcinoma: Experience of two tertiary hospitals in Southwestern China.

Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan-Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). Conclusions: Surgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.

Prognostic effects of previous cancer history on patients with major salivary gland cancer.

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

Low Bone Mineral Density and the Risk of Benign Paroxysmal Positional Vertigo.

OBJECTIVE: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population-based UK Biobank (UKB) cohort. STUDY DESIGN: Prospective population-based cohort study. SETTING: The UKB. METHODS: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. RESULTS: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow-up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P = .0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P = .0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. CONCLUSION: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV.

A Population-Based Outcome-Wide Association Study of the Comorbidities and Sequelae Following COVID-19 Infection.

BACKGROUND: Immense attention has been given to the outcome of COVID-19 infection. However, comprehensive studies based on large populational cohort with long-term follow-up are still lacking. This study aimed to investigate the risk of various short-term comorbidities (within one month) and long-term sequelae (above one month) after COVID-19 infection. METHODS: In this large prospective cohort study with 14 months follow-up information based on UK biobank, we included 16,776 COVID-19-positive participants and 58,281 COVID-19-negative participants matched for comparison. The risk of each comorbidity and sequela was evaluated by multivariable logistic regression analysis and presented as hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: COVID-19-positive individuals had a higher risk of 47 types of comorbidities within one month following COVID-19 infection, especially those who were older, male, overweight/obese, ever-smoked, with more pre-existing comorbidities and hospitalized. About 70.37% of COVID-19 patients with comorbidities had more than one co-occurring comorbidities. Additionally, only 6 high-risk sequelae were observed after one month of COVID-19 infection, and the incidence was relatively low (< 1%). CONCLUSION: In addition to long-term sequelae following COVID-19 infection, plenty of comorbidities were observed, especially in patients with older age, male gender, overweight/obese, more pre-existing comorbidities and severe COVID-19, indicating that more attention should be given to these susceptible persons within this period.

Associations Between Body Composition and Sensorineural Hearing Loss Among Adults Based on the UK Biobank.

OBJECTIVE: To explore the association between body composition and sensorineural hearing loss (SNHL). STUDY DESIGN: Cross-sectional study, prospective study and Mendelian randomization (MR) analyses. SETTING: UK Biobank. METHODS: This cross-sectional study included 147,296 adult participants with complete data on body composition and the speech-reception-threshold (SRT) test. We further conducted a prospective study with 129,905 participants without SNHL at baseline and followed up to 15 years to explore the association between body composition and new-onset SNHL. Multivariable logistic regression and Cox regression models were used. Subgroup analyses stratified by age and sex were performed. We further assessed the causal association between body composition and SNHL using two-sample MR analyses. RESULTS: Our cross-sectional study revealed that fat percentage, especially leg (odds ratio [OR] 1.46, p = .029) and arm (OR 1.43, p = .004), were significant risk factors for SNHL. However, fat-free mass, especially in the arm (OR 0.27, p < .001) and leg (OR 0.58, p < .001) showed significant protective effects against SNHL, which was substantially consistent with the results of the prospective study. In addition, we found that young women with SNHL were more susceptible to body composition indicators. However, MR analyses revealed no evidence of significant causal association. CONCLUSION: Fat percentage, especially in the leg and arm, was a significant risk factor for SNHL, whereas fat-free mass, especially in the leg and arm, had significant protective effects against SNHL, however, these associations may not be causal.

The role of HPV status in patients with overlapping grey zone cancer in oral cavity and oropharynx.

PURPOSE: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. METHODS: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database were compared to patients with oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by tenfold cross validation. RESULTS: A total of 3318 GZSCC, 10792 OPSCC and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) were the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. CONCLUSIONS: GZSCC patients had distinct clinical characteristics and prognosis compared with OPSCC and OCSCC, integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.

The Relationship Between Sleep Traits and Tinnitus in UK Biobank: A Population-Based Cohort Study.

OBJECTIVES: Understanding the association between sleep traits and tinnitus could help prevent and provide appropriate interventions against tinnitus. Therefore, this study aimed to assess the relationship between different sleep patterns and tinnitus. DESIGN: A cross-sectional analysis using baseline data (2006-2010, n = 168,064) by logistic regressions was conducted to evaluate the association between sleep traits (including the overall health sleep score and five sleep behaviors) and the occurrence (yes/no), frequency (constant/transient), and severity (upsetting/not upsetting) of tinnitus. Further, a prospective analysis of participants without tinnitus at baseline (n = 9581) was performed, who had been followed-up for 7 years (2012-2019), to assess the association between new-onset tinnitus and sleep characteristics. Moreover, a subgroup analysis was also carried out to estimate the differences in sex by dividing the participants into male and female groups. A sensitivity analysis was also conducted by excluding ear-related diseases to avoid their confounding effects on tinnitus (n = 102,159). RESULTS: In the cross-sectional analysis, participants with "current tinnitus" (OR: 1.13, 95% CI: 1.04-1.22, p = 0.004) had a higher risk of having a poor overall healthy sleep score and unhealthy sleep behaviors such as short sleep durations (OR: 1.09, 95% CI: 1.04-1.14, p < 0.001), late chronotypes (OR: 1.09, 95% CI: 1.05-1.13, p < 0.001), and sleeplessness (OR: 1.16, 95% CI: 1.11-1.22, p < 0.001) than those participants who "did not have current tinnitus." However, this trend was not obvious between "constant tinnitus" and "transient tinnitus." When considering the severity of tinnitus, the risk of "upsetting tinnitus" was obviously higher if participants had lower overall healthy sleep scores (OR: 1.31, 95% CI: 1.13-1.53, p < 0.001). Additionally, short sleep duration (OR: 1.22, 95% CI: 1.12-1.33, p < 0.001), late chronotypes (OR: 1.13, 95% CI: 1.04-1.22, p = 0.003), and sleeplessness (OR: 1.43, 95% CI: 1.29-1.59, p < 0.001) showed positive correlations with "upsetting tinnitus." In the prospective analysis, sleeplessness presented a consistently significant association with "upsetting tinnitus" (RR: 2.28, p = 0.001). Consistent results were observed in the sex subgroup analysis, where a much more pronounced trend was identified in females compared with the males. The results of the sensitivity analysis were consistent with those of the cross-sectional and prospective analyses. CONCLUSIONS: Different types of sleep disturbance may be associated with the occurrence and severity of tinnitus; therefore, precise interventions for different types of sleep disturbance, particularly sleeplessness, may help in the prevention and treatment of tinnitus.

Dynamic changes of hematological indices in oropharyngeal cancer patients treated with radiotherapy.

BACKGROUND: Hematological indices assist in predicting clinical outcomes. OBJECTIVES: To explore changes of hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients received radiotherapy and their association with survival. MATERIAL AND METHODS: The white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline, 1-, 3-, 6- and 12-months follow-up were retrospectively collected. The trajectory of indices was described. A linear model with random effects was to describe indices' changing rate and trend. Univariable Cox analysis was to assess the correlation between indices and survival. RESULTS: Of the 85 patients, WBC and ALC dropped during acute phase and gradually recovered, while NLR and PLR increased during acute phase and subsequently declined (all p < .01). Higher absolute value of nutritional indices (Alb and Hb) was associated with better prognosis (p < .05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (ANC, Plt, NLR and PLR) had worse survival (p < .05). CONCLUSIONS AND SIGNIFICANCE: The short- and long-term changes of indices differed in OPSCC patients received radiotherapy, and absolute values and dynamic changes of indices had the potential to be prognostic factors.

The Prognostic Prediction Value of Positive Lymph Nodes Numbers for the Hypopharyngeal Squamous Cell Carcinoma.

Background: The current American Joint Committee on Cancer (AJCC) system only considered the importance of the size and laterality of lymph nodes while not the positive lymph node number (PLNN) for hypopharyngeal squamous cell carcinoma (HPSCC). Methods: A total of 973 patients with HPSCC from the Surveillance, Epidemiology, and End Results database (2004-2015) were identified. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic effects. We applied six Cox regression models to compare the survival prognostic values of PLNN and AJCC systems. Results: Positive lymph node number showed a significant association with overall survival (OS) and cancer-specific survival (CSS) (P < 0.001) in univariate and multivariable analyses. The increased PLNN of HPSCC gave rise to poor OS and CSS. The survival model incorporating a composite of PLNN and TNM classification (C-index for OS:0.682, C-index for CSS:0.702) performed better than other models. Conclusions: A positive lymph node number could serve as a survival predictor for patients with HPSCC and a complement to enhance the prognostic assessment effects of TNM cancer staging systems.

Survival Outcomes Related to Treatment Modalities in Patients With Oropharyngeal Squamous Cell Carcinoma.

BACKGROUND: More patients with oropharyngeal squamous cell carcinoma (OPSCC) in Eastern countries receive surgically inclusive treatment (SIT), while most patients in Western countries receive nonsurgical treatment (NST). The optimal treatment modality for OPSCC patients remains controversial. METHODS: A total of 153 consecutive OPSCC cases diagnosed between 2009 and 2019 in West China Hospital (WCH) and 15,400 OPSCC cases from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2017) were obtained. Clinical characteristics, treatments, and survival outcomes were retrospectively collected. We constructed Kaplan-Meier curves and performed univariate (UVA) and multivariate (MVA) analyses to compare the prognosis of OPSCC patients among the WCH, SEER Asian, and SEER all ethnic populations by different treatment modality, human papilloma virus (HPV) infection status, age, and tumor stage. RESULTS: Overall, the proportions of patients with younger age, advanced tumors and HPV-negative status, and receiving SIT in WCH population were higher than those in the SEER all ethnic population, while the proportions in the SEER Asian population were between those of the other two populations. We observed consistent beneficial effects of SIT on the overall survival (OS) in OPSCC patients in all three populations (SEER Asian: MVA, hazard ratio (HR): 0.2, p < .001; SEER all ethnic: MVA, HR: 0.46, p < .001; WCH: UVA, HR: 0.62, p = .071), and HPV-negative Asian patients showed greater benefits from the SIT than HPV-positive Asian patients (HPV Negative: HR: 0.16, p = .005; HPV positive: HR = 0.28, p = .059). Male was a risk factor for reduced OS in OPSCC patients in the WCH population (HR: 3.17, p = .043), but was a protective factor in the SEER population (HR: 0.8, p = .002), which might be related to the differences of HPV infection status. CONCLUSIONS: Even though differences in patient characteristics existed between the Chinese, American, and Asian American populations, our ten-year real-world data and SEER data suggested that patients with OPSCC who received SIT had a better prognosis than those who received NST.

Impact of Allergic Rhinitis and Asthma on COVID-19 Infection, Hospitalization, and Mortality.

BACKGROUND: It remains unclear if patients with allergic rhinitis (AR) and/or asthma are susceptible to corona virus disease 2019 (COVID-19) infection, severity, and mortality. OBJECTIVE: To investigate the role of AR and/or asthma in COVID-19 infection, severity, and mortality, and assess whether long-term AR and/or asthma medications affected the outcomes of COVID-19. METHODS: Demographic and clinical data of 70,557 adult participants completed SARS-CoV-2 testing between March 16 and December 31, 2020, in the UK Biobank were analyzed. The rates of COVID-19 infection, hospitalization, and mortality in relation to pre-existing AR and/or asthma were assessed based on adjusted generalized linear models. We further analyzed the impact of long-term AR and/or asthma medications on the risk of COVID-19 hospitalization and mortality. RESULTS: Patients with AR of all ages had lower positive rates of SARS-CoV-2 tests (relative risk [RR]: 0.75, 95% confidence interval [CI]: 0.69-0.81, P < .001), with lower susceptibility in males (RR: 0.74, 95% CI: 0.65-0.85, P < .001) than females (RR: 0.8, 95% CI: 0.72-0.9, P < .001). However, similar effects of asthma against COVID-19 hospitalization were only major in participants aged <65 (RR: 0.93, 95% CI: 0.86-1, P = .044) instead of elderlies. In contrast, patients with asthma tested positively had higher risk of hospitalization (RR: 1.42, 95% CI: 1.32-1.54, P < .001). Neither AR nor asthma had an impact on COVID-19 mortality. None of conventional medications for AR or asthma, for example, antihistamines, corticosteroids, or ß2 adrenoceptor agonists, showed association with COVID-19 infection or severity. CONCLUSION: AR (all ages) and asthma (aged <65) act as protective factors against COVID-19 infection, whereas asthma increases risk for COVID-19 hospitalization. None of the long-term medications had a significant association with infection, severity, and mortality of COVID-19 among patients with AR and/or asthma.

Longitudinal health utility and symptom-toxicity trajectories in patients with head and neck cancers.

BACKGROUND: This study examined long-term health utility and symptom-toxicity trajectories among patients with head and neck cancer (HNC). METHODS: For patients diagnosed with HNC (2014-2019), Health Utility Index 3 (HUI-3), Edmonton Symptom Assessment Scale (ESAS), and MD Anderson Symptom Inventory (MDASI) surveys (including both the core and head and neck cancer modules) were prospectively collected at multiple time points (at the baseline, after surgery, during radiotherapy, and 3, 6, 12, and 24 months after treatment). Locally estimated scatterplot smoothing plots were generated to describe HUI-3, ESAS, and MDASI trajectories over time by clinicodemographic factors, treatment modality, and tumor subsite. Contributions of clinical factors were assessed with univariable and multivariable analyses. RESULTS: In 800 patients, the treatment modality and the tumor subsite produced unique HUI-3, ESAS, and MDASI trajectories. Patients treated with surgery alone experienced rapid improvements in HUI-3, ESAS, and MDASI scores postoperatively. Among patients treated with chemoradiotherapy, patients with nasopharyngeal carcinoma had greater declines in HUI-3 during treatment in comparison with patients with oropharyngeal carcinoma, but they had similar ESAS/MDASI scores. Among patients treated with radiotherapy, patients with laryngeal carcinoma had better HUI-3/ESAS/MDASI scores than those with oropharyngeal carcinoma during treatment, but they slowly converged after treatment. Female sex, an age > 75 years, a household income < $40,000, a Charlson comorbidity score > 1, an Eastern Cooperative Oncology Group performance status > 0 (at the baseline), and current smoking were independently associated with worse HUI-3 trajectories. HUI-3 had mild to moderate correlations (ρ = 0.2-0.5) with individual symptom-toxicity trajectories. CONCLUSIONS: Long-term HUI-3 trajectories are associated with tumor subsite, clinicodemographic, and treatment factors, and this may be partly explained by relationships with symptoms/toxicities. Separate evaluations by subsite and treatment should occur in health utility and symptom-toxicity studies of HNC. LAY SUMMARY: This study indicates that the long-term health utility and symptoms/toxicities of patients with the most common head and neck cancers (ie, squamous cell carcinomas and nasopharyngeal carcinomas) differ over time with a variety of factors, including the tumor anatomic site, treatment volume, clinicodemographic characteristics (eg, age, human papillomavirus status, tumor stage, gender, smoking status, alcohol status, education, and comorbidities), and treatment modalities. Generalizations across all head and neck cancers should be strongly discouraged. Future studies should evaluate health utility, symptoms and toxicities, and patient need assessments separately for each anatomic site and treatment modality.

Single-Cell Transcriptome Profiling Identifies Phagocytosis-Related Dual-Feature Cells in A Model of Acute Otitis Media in Rats.

Background: The molecular mechanisms of acute otitis media (AOM) development, and the intercellular crosstalk within the multicellular ecosystem of AOM, are not clear. Methods: We established a model of AOM in rats (with normal rats as controls) and undertook single-cell RNA sequencing (scRNA-seq) for the middle-ear mucosa (MEM). Cell clustering and trajectory analyses were undertaken using Seurat and Monocle 2 packages in R software. Pathway analyses were done by gene set enrichment analysis (GSEA). Cell-cell interactions were inferred by CellChat. Cell scores were calculated to identify cells with dual-feature. Results: A total of 7023 cells from three samples of inflamed MEM and 5258 cells from three samples of healthy MEM underwent scRNA-seq, which identified 20 cell clusters belonging to eight major cell types. After exposure to lipopolysaccharide, the MEM underwent significant conversion of cell types characterized by rapid infiltration of macrophages and neutrophils. M2 macrophages seemed to play a key part in inflammatory intercellular crosstalk, which facilitated the maintenance and proliferation of macrophages, cell chemotaxis, and regulation of the proinflammatory activities of cytokines. Three rare cell clusters with phagocytosis-related dual-feature were also identified. They coexisted with professional phagocytes in the MEM, and displayed distinct immunoregulatory functions by maintaining a normal immune microenvironment or influencing inflammation progression. Conclusions: Macrophages might be the "master" initiators and regulators of the inflammatory response of the MEM to external stimuli. And their functions are fulfilled by a specific polarization status (M2) and sophisticated intercellular crosstalk via certain signaling pathways. Besides, the coexistence of professional phagocytes and non-professional phagocytes as well as their interplay in the MEM provides new clues for deciphering the underlying pathogenic mechanisms of AOM.

Diagnostic and Prognostic Value of MicroRNAs in Metastasis and Recurrence of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

MicroRNAs have been proven to make remarkable differences in the clinical behaviors of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically analyze whether differential expression levels of microRNAs are related to recurrence or metastasis in patients with HNSCC. A comprehensive search of the PubMed, EMBASE, and CENTRAL was conducted up to July 24th, 2021. Data were collected and combined from studies reporting recurrence-free survival (RFS) of HNSCC patients with high microRNA expression compared to those with low expression. Besides, studies providing necessary data for evaluating the diagnostic value of microRNAs for detecting recurrence and metastasis based on their expression levels were also included and combined. The pooled hazard ratio (HR) value for the outcomes of RFS in 1,093 HNSCC samples from 10 studies was 2.51 (95%CI: 2.13-2.96). A sensitivity of 0.79 (95% CI: 0.72-0.85) and specificity of 0.77 (95%CI: 0.68-0.83) were observed in three studies, of which 93 patients with recurrence and 82 nonrecurrence controls were included, and the area under the curve (AUC) was 0.85 (95% CI: 0.81-0.88). Additionally, high diagnostic accuracy of microRNAs in detecting lymph node metastasis (LNM) was also reported. In conclusion, two panels of microRNAs showed the potential to predict recurrence or diagnose recurrence in HNSCC patients, respectively, which could facilitate prognosis prediction and diagnosis of clinical behaviors in HNSCC patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (https://www.crd.york.ac.uk/prospero), identifier CRD42020161117.

Evaluating the prognostic contributions of TNM classifications and building novel staging schemes for middle ear squamous cell carcinoma.

BACKGROUND: A universally acknowledged cancer staging system considering all aspects of the T-, N-, and M-classifications for middle ear squamous cell carcinoma (MESCC) remains absent, limiting the clinical management of MESCC patients. MATERIALS AND METHODS: A total of 214 MESCC patients were extracted from the SEER (the Surveillance, Epidemiology, and End Results) database between 1973 and 2016. The relationships between patient's characteristics and prognoses were analyzed by Kaplan-Meier and Cox proportional hazards regression models. Novel staging schemes for MESCC were designed by adjusted hazard ratio (AHR) modeling method according to the combinations of Stell's T-classification and the eighth AJCC N- and M-classifications, of which performances were evaluated based on five criteria: hazard consistency, hazard discrimination, explained variation, likelihood difference, and balance. RESULTS: T-classification was the most significant prognostic factor for MESCC patients in multivariable analysis (p = 0.021). The N- and M-classifications also had obvious prognostic effect but were not statistically significant by multivariate analysis due to the limited metastasis events. Three novel staging schemes (AHR-Ⅰ-Ⅲ models, different combination of T- and N-classifications) and ST (solely derived from Stell's T-classification) were developed, among which the AHR-Ⅰ staging scheme performed best. CONCLUSIONS: Tumor extension, quantified by Stell's T-classification, is the most significant prognostic factor for MESCC patients. However, our AHR-Ⅰ staging scheme, a comprehensive staging scheme that integrating T-, N-, and M-classifications, might be an optimal option for clinical practitioners to predict MESCC patients' prognosis and make proper clinical decisions.

Combination of Modified Free Anterolateral Thigh Skin-Fascia Flap and Pedicled Thoracoacromial Artery Perforator Flap for Entire Circumferential Pharyngoesophageal Defect and External Neck Skin Defect Reconstructions.

Simultaneous reconstructions of entire circumference pharyngoesophageal defect and external neck skin defect are challenges for head and neck surgeons. A 57-year old man, who underwent radical tumor resection, suffered with an advanced metachronous second primary esophageal squamous cell carcinoma (SPESCC). Our modified operative technique (mALT-TAAP), a combination of modified free anterolateral thigh (ALT) flap (a fasciocutaneous flap with an extension of fascia) and pedicled thoracoacromial artery perforator (TAAP) flap, was utilized to reconstruct the entire circumference of pharyngoesophageal and external neck skin defect reconstructions. The modified ALT flap, TAAP flap and donor wounds recovered well postoperatively. No morbidity of the donor site or operation-related complication was observed. The postoperative recovery of swallowing function was satisfactory. Our mALT-TAAP reconstruction method could be a decent option for simultaneous reconstructions of entire circumference of pharyngoesophageal defect and external neck skin defect.

Clinical outcomes of different treatments and risk factors in patients with otogenic brain abscess, a real-world evidence-based retrospective study.

BACKGROUND: Otogenic Brain Abscess (OBA) is a life-threatening complication secondary to otitis media, but its appropriate management remains controversial. OBJECTIVES: To understand the demographic characteristics, management, and variables that affect the outcomes of patients with OBA based on our experiences over 11 years. MATERIAL AND METHODS: Clinical data were collected for 41 patients. Prognostic factors associated with mortality were assessed, and clinical outcomes compared among groups receiving different treatments. RESULTS: Among the 41 patients, 19.6% did not undergo surgery, 39.0% were treated with two-stage surgery (otological surgery and neurosurgery) and 41.4% were treated with single-stage surgery (otological surgery or neurosurgery). Overall mortality rate was 32.5%, and mortality was significantly higher in patients with invasion of the petrous apex (odds ratio [OR]: 7.81, 95% confidence interval [95% CI]: 1.26-48.36), and lower in those with appropriate surgical management (single otological surgery, OR: 0.07, 95% CI: 0-0.97; single neurosurgery, OR: 0.13, 95% CI: 0.02-1.0; two-stage surgery, OR: 0.08, 95% CI: 0.01-0.64) or a higher Glasgow Coma Scale (GCS) score at admission (OR: 0.64, 95% CI: 0.44-0.93). CONCLUSIONS AND SIGNIFICANCE: Data on invasiveness and pre-surgery GCS greatly aid in predicting the prognosis of OBA patients. Early evaluation will facilitate decision-making by physicians treating OBA patients.

Growing Skull Fracture of Temporal Bone in Adults: A Case Report and Literature Review.

Growing skull fracture (GSF) is an uncommon post-traumatic complication, which accounts for approximately 0.05% to 1% of all skull fractures. Delayed diagnosis of GSF in adulthood is rare and often involved with a variety of neurological symptoms. Here, we reported an adult patient, with an interval of 17 years from initial head trauma to first diagnosis of GSF. The patient complained of short periods of fainting and bilateral visual hallucinations, with a hard palpable bulge around his right occipitomastoid suture region. Computed tomographic imaging demonstrated an arachnoid cyst extending into right mastoid cavity. Consequently, the delayed diagnosis of GSF was confirmed, and the patient was managed with duroplasty and cranioplasty. At the 8-month follow-up, the patient showed an uneventful postoperative recovery. A comprehensive literature review was also conducted, and a total of 70 GSF cases were identified and summarized. According to the literature review, patients with GSF generally have a history of head trauma in their childhood, and delayed diagnosis is a common situation. Diagnosis of GSF should include complete retrospective medical history, physical, and imaging examinations. Once the diagnosis is confirmed, cranioplasty accompanied with duroplasty might be the most effective way to relieve symptoms and prevent further damage.