The expression of nicotinic acetylcholine receptor subunits and their associations with local immune cells and prognosis in oral squamous cell carcinoma.

BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that may be responsible for cancer cell proliferation, epithelial-mesenchymal transition (EMT), and immune regulation. However, little is known about the associations of different nAChR subunits with tumor microenvironment in oral squamous cell carcinoma (OSCC). METHODS: We retrospectively reviewed pathology samples from 75 OSCC patients by immunohistochemistry. In addition, a cohort of 307 OSCC patients in The Cancer Genome Atlas was analyzed. RESULTS: Subunit α1 was specific to peri-OSCC skeletal muscle. Increased α1 was associated with increased CD44 (cancer stem cells), increased CD3 and 8 (T cells), increased CD56 and 16 (natural killer cells), a decreased T stage, and an increased N stage. Increased α3 was associated with increased CD56 and 16. Increased α5 was associated with decreased CD3, 8, and 56, a decreased T stage, an increased N stage, worse survival, and decreased epithelial features. Increased α7 was associated with increased CD3, 8, 56, and 16, decreased tumor/peritumor ratios of CD3, 8, and 56 immune cells, and increased epithelial features. Increased local immune cells were associated with a better prognosis. CONCLUSIONS: α5 is the only subunit associated with decreased local immune cells and worse survival, while α1, α3, and α7 are associated with increased local immune cells in OSCC. α5 and α7 are correlated with different EMT states to be mesenchymal-like and epithelial-like OSCC, respectively. Protein expression data of the nAChR subunits, complementary to gene expression data, could provide meaningful information regarding the EMT status of OSCC associated with immune responses and prognosis.

Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Upfront high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) remains a profitable strategy for newly diagnosed multiple myeloma (MM) patients in the context of novel agents. However, current knowledge demonstrates a discrepancy between progression-free survival (PFS) and overall survival (OS) benefit with HDT/ASCT. METHODS: We conducted a systematic review and meta-analysis that included both randomized controlled trials (RCTs) and observational studies evaluating the benefit of upfront HDT/ASCT published during 2012 to 2023. Further sensitivity analysis and meta-regression were also performed. RESULTS: Among the 22 enrolled studies, 7 RCTs and 9 observational studies had a low or moderate risk of bias, while the remaining 6 observational studies had a serious risk of bias. HDT/ASCT revealed advantages in complete response (CR) with an odds ratio (OR) of 1.24 and 95% confidence interval (CI) 1.02 ~ 1.51, PFS with a hazard ratio (HR) of 0.53 (95% CI 0.46 ~ 0.62), and OS with an HR of 0.58 (95% CI 0.50 ~ 0.69). Sensitivity analysis excluding the studies with serious risk of bias and trim-and-fill imputation fundamentally confirmed these findings. Older age, increased percentage of patients with International Staging System (ISS) stage III or high-risk genetic features, decreased proteasome inhibitor (PI) or combined PI/ immunomodulatory drugs (IMiD) utilization, and decreased follow-up duration or percentage of males were significantly related to a greater survival advantage with HDT/ASCT. CONCLUSIONS: Upfront ASCT remains a beneficial treatment for newly diagnosed MM patients in the period of novel agents. Its advantage is especially acute in high-risk MM populations, such as elderly individuals, males, those with ISS stage III or high-risk genetic features, but is attenuated with PI or combined PI/IMiD utilization, contributing to divergent survival outcomes.

The expression and prognostic impact of proinflammatory cytokines and their associations with carcinogens in oropharyngeal squamous cell carcinoma.

In oropharyngeal squamous cell carcinoma (OPSCC), the relationships between immune responses, carcinogens, and prognoses are not clarified yet. Here, we retrospectively reviewed the pathology samples of 46 OPSCC patients, and used p16 to determine their human papillomavirus (HPV) status. The Cancer Genome Atlas (TCGA) database was also analyzed for further comparison. The immunofluorescence staining of proinflammatory cytokines showed that high interferon gamma (IFNγ; T helper 1; Th1), low interleukin 4 (IL4; T helper 2; Th2), low thymic stromal lymphopoietin (TSLP; Th2), and low transforming growth factor beta (TGFß; T regulatory; Treg) expressions were good prognostic factors for OPSCC. p16-positive OPSCC showed higher Th1, lower Th2/Treg proinflammatory cytokine expressions, and a better prognosis than p16-negative OPSCC. In smokers alone, although p16-positive OPSCC smokers showed weaker Th2/Treg predominant cytokine expressions than p16-negative OPSCC smokers, the prognoses of both groups were equally poor. As for p16-positive OPSCC patients alone, p16-positive nonsmokers showed a significantly better prognosis than p16-positive smokers, but the immune responses of both groups were all weakly Th2/Treg predominant. Overall, higher Th1 and lower Th2/Treg proinflammatory cytokine expressions are associated with a better prognosis for OPSCC. HPV may be related to increased Th1, decreased Th2/Treg responses, and a good prognosis, while smoking may be related to increased Th2/Treg, decreased Th1 responses, and a poor prognosis in OPSCC. The impact of smoking on immune deviation may be weaker than that of HPV, but the impact of smoking on prognosis may be stronger than that of HPV in OPSCC.

The application of ultrasound in detecting lymph nodal recurrence in the treated neck of head and neck cancer patients.

Early detection of neck lymph node (LN) recurrence is paramount in improving the prognosis of treated head and neck cancer patients. Ultrasound (US) with US-guided fine needle aspiration (FNA) and core needle biopsy (CNB) have been shown to have great accuracy for LN diagnoses in the untreated neck. However, in the treated neck with fibrosis, their roles are not clarified. Here, we retrospectively review 153 treated head and neck cancer patients who had received US and US-guided FNA/CNB. In multivariate logistic regression analyses, size (short-axis diameter >0.8 cm) (odds ratio (OR) 4.19, P = 0.007), round shape (short/long axis ratio >0.5) (OR 3.44, P = 0.03), heterogeneous internal echo (OR 3.92, P = 0.009) and irregular margin (OR 7.32, P < 0.001) are effective US features in predicting recurrent LNs in the treated neck. However, hypoechogenicity (OR 2.38, P = 0.289) and chaotic/absent vascular pattern (OR 3.04, P = 0.33) are ineffective. US-guided FNA (sensitivity/specificity: 95.24%/97.92%) is effective in the treated neck, though with high non-diagnostic rate (29.69%). US-guided CNB (sensitivity/specificity: 84.62%/100%) is also effective, though with low negative predictive value (62.5%). Overall, US with US-guided FNA/CNB are still effective diagnostic tools for neck nodal recurrence surveillance.

Identifying the affected branches of vestibular nerve in vestibular neuritis.

CONCLUSION: The inner ear monitoring system is useful for identifying the affected branches of the vestibular nerve in cases of vestibular neuritis, providing insight about the interval for the relief of vertigo. OBJECTIVE: This study conducted an inner ear monitoring system including audiometry, and caloric, ocular vestibular evoked myogenic potential (oVEMP), and cervical VEMP (cVEMP) tests in cases of vestibular neuritis for assessing the affected branches of the vestibular nerve. METHODS: Twenty patients with vestibular neuritis underwent caloric, oVEMP, and cVEMP tests. Type I indicates that one of the three tests is abnormal; type II indicates that two test results are abnormal; and type III indicates that no test result is normal. RESULTS: All patients had normal hearing, bilaterally. Nineteen (95%) of 20 patients had abnormal caloric responses, 11 patients (55%) had abnormal oVEMPs, and 5 patients (25%) had abnormal cVEMPs. Restated, of all 20 patients, 8 patients were classified as type I, 9 were type II, and 3 were type III. The mean intervals between presentation and relief of vertigo were significantly different among the three types. One year after treatment, caloric, oVEMP, and cVEMP tests returned to normal responses in three (60%) of five patients.

Ocular vestibular evoked myogenic potentials via bone-conducted vibrations applied to various midsagittal cranial sites.

OBJECTIVE: This study applied bone-conducted vibration (BCV) stimulation to various midsagittal sites on the cranium to optimize stimulation conditions for ocular vestibular evoked myogenic potentials (oVEMPs). STUDY DESIGN: Ten healthy subjects (7 men and 3 women, aged 25-32 yr) without previous ear disorders were enrolled in this study. Each subject underwent oVEMP test using BCV applied to 4 cranial sites on the midsagittal plane, namely, the Fpz (above the glabella), Fz (the midline forehead at the hairline), Cz (vertex), and inion. In addition, the linear distances from the vestibule to the 4 sites were measured via multiplanar reconstruction of computed tomographic scans. SETTING: Tertiary referral university hospital. RESULTS: All 10 subjects showed 100% clear oVEMPs at the Fpz, Fz, inion, and Cz sites. The mean +/- SD nI latencies of these 4 sites were 8.9 +/- 0.8, 9.8 +/- 2.4, 11.2 +/- 1.5, and 14.0 +/- 2.0 milliseconds, respectively, exhibiting significant differences among the 4 sites. The median (range) nI-pI amplitudes of oVEMPs stimulated via the Fpz, Fz, inion, and Cz sites were 15.8 microV (4.2-55.8 microV), 9.9 microV (3.8-29.0 microV), 11.5 microV (5.5-58.0 microV), and 6.1 microV (2.5-21.4 microV), respectively, indicating significant differences among the 4 sites. Of them, the oVEMPs elicited by BCV mode at the Fpz represented the largest nI-pI amplitude, when compared with the other 3 sites. Furthermore, the linear distances from the vestibule to the Fpz, Fz, inion, and Cz sites were 10.7 +/- 0.4, 11.5 +/- 0.5, 8.6 +/- 0.4, and 12.0 +/- 0.5 cm, respectively. The inion site had the shortest distance to the vestibule, but it did not show the earliest nI latency. CONCLUSION: The Fpz may be the optimal site for BCV stimulation for screening oVEMPs in reflex magnitude.