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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.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Salivares , Humanos , Feminino , Masculino , Prognóstico , Neoplasias das Glândulas Salivares/patologia , Carcinoma de Células Escamosas/patologiaRESUMO
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.
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Otopatias , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Zumbido , Humanos , Masculino , Feminino , Zumbido/terapia , Estudos Transversais , Bancos de Espécimes Biológicos , Estudos de Coortes , Sono , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Reino Unido/epidemiologiaRESUMO
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.
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Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Carcinoma de Células Escamosas/patologia , Prognóstico , Boca/patologiaRESUMO
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.
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Doenças Ósseas Metabólicas , Osteoporose , Idoso , Humanos , Feminino , Pessoa de Meia-Idade , Vertigem Posicional Paroxística Benigna/complicações , Vertigem Posicional Paroxística Benigna/diagnóstico , Estudos Prospectivos , Densidade Óssea , Estudos de Coortes , Doenças Ósseas Metabólicas/complicações , Osteoporose/complicações , Hormônios Esteroides GonadaisRESUMO
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.
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Tumor-infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion-related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune-promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor-infiltrating CD4+ T cells were identified, and both the immune-promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD-1) and Treg cells in Module 2 (αCTLA-4) in mouse models could help reinvigorate the effector function of Module 1-exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2-exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.
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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.
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OBJECTIVES: This study aimed to investigate the survival outcomes and potential prognostic factors of patients with temporal bone squamous cell carcinoma (TBSCC) treated at our institution. METHODS: We retrospectively included patients who were diagnosed with TBSCC between 2008 and 2019. The Kaplan-Meier (KM) method was used to describe overall survival (OS), and the association between baseline characteristics and prognoses was examined using Cox proportional hazards models. RESULTS: Fifty consecutive patients with TBSCC were included in this study. The results showed that patients with advanced modified Pittsburgh (MPB)- T classifications had a poorer prognosis (T3 vs. T1-2: HR: 2.81, 95% CI: 0.34-23.43; T4 vs. T1-2: HR: 7.25, 95% CI: 0.95-55.41; p = 0.041). Meanwhile, middle ear squamous cell carcinoma (MESCC) showed a significantly worse prognosis than external auditory canal squamous cell carcinoma (EACSCC, HR: 2.65, 95% CI: 1.04-6.76, p = 0.04). CONCLUSIONS: MESCC and advanced MPB-T classifications might be considered predictors of unfavorable outcomes in patients with TBSCC, indicating that special attention should be paid to the original tumor subsite and tumor extension in the management of patients with TBSCC.
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Carcinoma de Células Escamosas , Neoplasias da Orelha , Neoplasias de Cabeça e Pescoço , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias da Orelha/patologia , Neoplasias de Cabeça e Pescoço/patologia , Osso Temporal/patologiaRESUMO
OBJECTIVES: To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases. DESIGN: Retrospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 500 371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex. EXPOSURE: Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively. RESULTS: During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p<0.001; male: HR=1.66, 95% CI=1.41 to 1.97, p<0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95% CI=1.47 to 2.11, p<0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95% CI=3.32 to 11.04, p<0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups. CONCLUSION: In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases.
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Hipersensibilidade , Infecções por Papillomavirus , Feminino , Masculino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Bancos de Espécimes Biológicos , Estudos Retrospectivos , Papillomavirus Humano , Reino Unido/epidemiologiaRESUMO
OBJECTIVE: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity (NC), nasopharynx, and paranasal sinuses, which are always categorized as one sinonasal type. STUDY DESIGN: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from Surveillance, Epidemiology, and End Results (SEER) database were included (1975-2017). SETTING: Population-based cohort study. METHODS: We conducted univariate and multivariate Cox regressions and Kaplan-Meier analysis to examine survival outcomes of B/NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses, respectively. RESULTS: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the cancer-special survival (CSS) outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (Hazard ratio [HR]: 3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of a higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in the nasopharynx NKT-NHL. However, chemotherapy has only been beneficial for CSS in patients with paranasal sinuses B-NHL (HR: 0.42) since 2010, rather than in other types of B/NKT-NHL. CONCLUSION: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinicodemographics and prognoses are largely different and should be treated and studied as distinct diseases.
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Linfoma não Hodgkin , Neoplasias Nasais , Neoplasias dos Seios Paranasais , Seios Paranasais , Humanos , Cavidade Nasal/patologia , Estudos de Coortes , Neoplasias dos Seios Paranasais/terapia , Neoplasias dos Seios Paranasais/patologia , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/patologia , Nasofaringe , Neoplasias Nasais/terapia , Neoplasias Nasais/patologiaRESUMO
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.
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Bancos de Espécimes Biológicos , Perda Auditiva Neurossensorial , Adulto , Feminino , Humanos , Composição Corporal , Estudos Transversais , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/etiologia , Estudos Prospectivos , Reino Unido/epidemiologia , Análise da Randomização MendelianaRESUMO
Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.
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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.
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COVID-19 , Humanos , Masculino , COVID-19/epidemiologia , Estudos Prospectivos , Sobrepeso/epidemiologia , SARS-CoV-2 , Comorbidade , Progressão da Doença , Obesidade/epidemiologiaRESUMO
BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.
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Refluxo Gastroesofágico , Refluxo Laringofaríngeo , Humanos , Pepsina A/análise , Pepsinogênio A/análise , Pepsinogênio A/metabolismo , Cromatografia Líquida , Saliva , Espectrometria de Massas em Tandem , Refluxo Gastroesofágico/diagnósticoRESUMO
The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Papillomavirus Humano , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Escamosas/metabolismoRESUMO
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.
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OBJECTIVES: This study aims to explore the gender-specific association between obstructive sleep apnea (OSA) and cognitive impairment. METHODS: Participants from UK biobank who have completed at least one of the five baseline cognitive tests (visuospatial memory, prospective memory, fluid intelligence, short numeric memory and reaction time) were included, which were initially divided into two groups based on gender and were further categorized into three subgroups: (1) OSA, (2) self-reported snoring but without OSA, and (3) healthy controls (without OSA or snoring). Multivariable regression analysis was performed to examine the associations among snoring, OSA and performance of each of the five cognitive domains. RESULTS: A total of 267,889 participants (47% male, mean age: 57 years old) were included in our study. In the multivariable regression analysis, female participants in the OSA group had a higher risk of having poor prospective memory (OR: 1.24, 95% CI: 1.02ï½1.50, p = 0.03). Meanwhile, among female participants, OSA were inversely associated with the performances of fluid intelligence (ß: 0.29, 95% CI: 0.46ï½-0.13, p < 0.001) and short-numeric memory (ß: 0.14, 95% CI: 0.35ï½0.08, p = 0.02). Besides, age-related subgroup analyses showed that these associations were largely reserved in younger (ï¼65 years old) female participants rather than older (≥65 years old) female participants. In contrast, among male participants, no significant association was observed between OSA and impairment of the five cognitive domains. CONCLUSIONS: OSA was significantly associated with cognitive impairment at certain dimensions in female participants rather than in male participants, indicating that more special attention and timely interventions should be given to younger female OSA patients to prevent further cognitive impairment.
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Disfunção Cognitiva , Apneia Obstrutiva do Sono , Adulto , Idoso , Disfunção Cognitiva/complicações , Feminino , Humanos , Masculino , Transtornos da Memória/complicações , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polissonografia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Ronco/complicaçõesRESUMO
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.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Humanos , Estudos Retrospectivos , Linfócitos/patologia , Contagem de Linfócitos , Prognóstico , Plaquetas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/patologiaRESUMO
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.
RESUMO
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.