Systemic bevacizumab for treatment of recurrent respiratory papillomatosis.

OBJECTIVES: To characterize treatment response of recurrent respiratory papillomatosis (RRP) including adult-onset RRP (AORRP) and juvenile-onset RRP (JORRP) to systemic bevacizumab (bev), and share our treatment regimen experience. METHODS: Patients were enrolled in bev treatment based on a pathologically confirmed diagnosis of squamous papilloma. According to lesion characteristics and medical history, systemic bev was used as preoperative adjuvant therapy, postoperative adjuvant therapy, or primary therapy. The assessment of treatment response relied on the morphological changes of lesions. Vocalization and voice-related quality of life were evaluated using the voice handicap index-30 (VHI-30) for adults and the pediatric VHI (pVHI) for children. Adverse effect was monitored through patient self-reported symptoms and regular follow-ups. RESULTS: This study included 24 patients, comprising nine AORRP and 15 JORRP cases. In AORRP, all patients (100%) exhibited various degrees of response to systemic bev, with 5 (55.56%) achieving complete response (CR). Among JORRP patients, 14 (93.33%) showed a response to systemic bev, with 8 (53.33%) achieving CR and currently being followed up. No instances of aggravation were observed during systemic bev treatment. A total of 21 patients (21/24, 87.50%) reported voice improvement, accompanied by reduced VHI-30 or pVHI scores across all aspects, including total, functional, physical, and emotional dimensions. No grade 3 or higher adverse events occurred. The most common adverse events were grade 1 gum bleeding (n = 4, 16.67%) and grade 1 proteinuria (n = 4, 16.67%). CONCLUSIONS: Systemic bev can be used as a powerful therapy for both AORRP and JORRP. The findings provide a reference to the systemic bev treatment for RRP.

Office-based 532-nm KTP laser as a therapeutic modality for recurrent laryngeal papillomatosis: efficacy and relative factors.

This study aims to investigate the efficacy of office-based potassium-titanyl-phosphate (KTP) 532-nm laser in the management of recurrent laryngeal papillomatosis (RLP) following other treatments. A retrospective assessment was performed on 55 patients in 259 cases of RLP between 2012 and 2019. Derkay scores were obtained for all patients who underwent 532-nm KTP laser procedure (6 W of power with a continuous output mode) prior to treatment and after treatment. Analysis of parameters is based on the distribution characteristics of data. An ordinal logistic regression was also performed. Patients received a median of 3 (range 1-24) office-based KTP laser treatments. Among them, 96.36% (53 patients) were previously on cold steel equipment, CO2 laser, or microdebrider treatment under general anesthesia, and all previous treatments on them had failed. One patient progressed to invasive cancer, so he was excluded from the following analyses. After final KTP treatment, 36 patients (66.67%) received complete resolution with follow-up time ranging from 12.9 to 80.53 months (median 55.54 months). Results of subjective voice-quality indicators such as VHI-30 and GRBAS all improved greatly at the last follow-up. The initial Derkay scores and treatment intervals were found to be predictive of complete lesion remission. Arytenoid involvement may also correlate with lesion resolution. Serial office-based KTP treatment is an effective option for RLP patients, with ideal disease control and voice quality preservation. KTP laser therapy should be repeated with an interval of 1 month from the beginning of treatment until the lesion has been evaluated and subsided. Non-bulk or scattered laryngeal papilloma is an appropriate indication for KTP laser treatment.

Morphology-guided treatment of adult laryngeal and hypopharyngeal hemangioma: FD-EENT experience.

OBJECTIVES: To investigate the clinical outcomes of morphology-guided surgical treatment for adult laryngeal and hypopharyngeal hemangioma. MATERIALS AND METHODS: Patients diagnosed with adult laryngeal and hypopharyngeal hemangioma by outpatient laryngoscopy and received surgical treatments were retrospectively included. Size and morphology were classified to guide the choose of surgical procedures including CO2 laser excision, CO2 coagulation + bleomycin injection and potassium-titanyl-phosphate (KTP) laser + bleomycin injection. The baseline information and pre-, postoperative laryngoscopies were collected, the outcomes were followed up and analyzed. RESULTS: A total of 68 patients were included, 7 cases with exophytic and non-bulky hemangioma received CO2 laser excision, 20 cases received CO2 laser coagulation + bleomycin injection and 25 cases with KTP + bleomycin injection, another 16 cases with pure bleomycin injection were included as comparison. There was no difference of baseline analysis among the groups (P > = 0.05). Positive outcomes were achieved in most cases of CO2 excision (100%), CO2 coagulation + bleomycin (90.0%) and KTP + bleomycin (84.0%) groups, which were better than pure bleomycin (56.3%, p = 0.001). CO2 or KTP, associated to Bleomycin, gave same results on same lesions (P = 0.132). CONCLUSIONS AND SIGNIFICANCE: Morphology of hemangioma may help in the selection of surgical procedures. CO2 coagulation can be used as a potential substitute for KTP in the treatment of adult laryngeal and hypopharyngeal hemangioma.

Clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease, RDD).

PURPOSE: To investigate the clinical features, diagnosis, treatment and prognosis of otolaryngological extranodal RDD. METHODS: A retrospective analysis was performed on 16 patients who were initially diagnosed and treated with otolaryngological extranodal RDD in our hospital from January 2013 to January 2019. RESULTS: There were 9 females and 7 males. The mean diagnostic age was 45.35. Nasal, laryngeal and otic RDD were, respectively, accounting for 56.25%, 31.25% and 12.5%. The median interval diagnostic time was individually 1, 0.5 and 0.2 year for nasal, laryngeal and otic RDD. The most common symptoms were separately progressive nasal congestion, dyspnea, otorrhea in nasal, laryngeal and otic RDD. 13 had cervical lymph node swelling on MRI. Surgery or postoperative radiotherapy were conformed. In the end, 14 patients with RDD survived. The survival rate is as high as 87.5%. One of them died of RDD in the fifth year. One case was lost to follow-up 2 years after treatment. Patients survive for at least 2 years and up to 9 years. There was no significant difference in life expectancy of extranodal RDD among different parts of ENT (P = 0.508 > 0.05). The average ages of laryngeal and nasal RDD were similar (P = 0.898 > 0.05). However, the age of both was significantly higher than ear RDD (P = 0.023 and 0.019 < 0.05). CONCLUSIONS: The average diagnostic age was more than 20 years. Nasal RDD was the most common in this area. All laryngeal RDD had infiltrated subglottis. Functional surgery and postoperative radiotherapy can be used to achieve long-term remission and survival.

Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: An Overview of Systematic Reviews.

Background: Hematopoietic stem cell transplantation (HSCT) has become the main treatment for acute myeloid leukemia (AML) and has been studied in many systematic reviews (SRs), but strong conclusions have not been drawn yet. Objective: This study aimed to summarize and critically evaluate the methodological and evidence quality of SRs and meta-analysis on this topic. Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched for SRs/meta-analyses regarding HSCT for AML. Two reviewers assessed the quality of SRs/meta-analyses in line with AMSTAR-2 and evaluated the strength of evidence quality with the grading of the evaluation system (GRADE) for concerned outcomes independently. Results: 12 SR/Meta articles were included, and the AMSTAR-2 scale showed that the quality grade of all articles was low or very low. GRADE results showed 29 outcomes, 2 of which were high, 12 were moderate, and 15 were low. Limitations and inconsistency were the most important factors leading to degradation, followed by imprecision and publication bias. Allo-SCT had better OS and DFS benefits than auto-SCT and significantly reduced the relapse in intermediate-risk AML/CR1 patients. Auto-SCT was associated with lower TRM than allo-SCT but generally had higher relapse. The results should be confirmed further for the low or moderate evidence quality. Conclusion: Current SRs show that allo-SCT in the treatment of AML might improve the OS, RFS, and DFS. Auto-SCT has significantly lower TRM but higher RR. Whether bone marrow transplantation is superior to nonmyeloablative chemotherapy remains to be evaluated. Meanwhile, the quality of methodology needs to be further improved. The intensity of evidence was uneven, and the high-quality evidence of outcomes was lacking. Considering the limitations of our overview, more rigorous and scientific studies are needed to fully explore the efficacy of different interventions of HSCT in AML, and clinicians should be more cautious in the treatment.

The Role of Keratin-8 and Keratin-18 Polymorphisms and Protein Levels in the Occurrence and Progression of Vocal Leukoplakia.

OBJECTIVE: This study aimed to evaluate the association between the single-nucleotide polymorphism (SNP) and tissue protein level of keratin-8/18 and the occurrence and progression of vocal leukoplakia. METHODS: The case-control study enrolled 158 patients with vocal leukoplakia, 326 patients with laryngeal squamous cell carcinoma (LSCC), and 268 healthy controls, which were tested for genotype analysis with keratin-8 and keratin-18 gene polymorphisms using pyrosequencing. The tissue protein expression levels of keratin-8 and keratin-18 were evaluated using immunohistochemistry. RESULTS: The keratin-8 SNP RS1907671 showed an obvious increased risk for vocal leukoplakia (OR 1.56, p = 0.002), while the other SNPs (RS2035875, RS2035878, RS4300473) were tested as protective factors for vocal leukoplakia and LSCC (OR <1, p < 0.05). In keratin-18 SNP test, both RS2070876 and RS2638526 polymorphisms demonstrated decreased risks for vocal leukoplakia and LSCC (OR <1, p < 0.05). The protein levels of keratin-8 and keratin-18 in vocal leukoplakia group were significantly higher than those of the LSCC group (p < 0.05). CONCLUSIONS: Keratin-8 and keratin-18 polymorphisms and protein levels are associated with the occurrence and progression of vocal leukoplakia.

Andrographolide sensitizes Hep-2 human laryngeal cancer cells to carboplatin-induced apoptosis by increasing reactive oxygen species levels.

Andrographolide is a natural diterpenoid from Andrographis paniculata that has been proposed as an anticancer agent as well as a chemosensitizer for use in combination with anticancer drugs. Carboplatin is the first-line chemotherapeutic agent for advanced laryngeal carcinoma. However, the clinical efficacy of carboplatin is limited by drug resistance and side effects. The aim of this study was to investigate whether andrographolide has a synergistic antitumor effect with carboplatin on human laryngeal cancer cells. Hep-2 cells were exposed to andrographolide with or without carboplatin. The effects of indicated therapies were examined using the Cell Counting Kit-8 assay, the colony-forming assay, the Hoechst 33342/PI double staining, and flow cytometry analysis. The molecular mechanism was assessed by reactive oxygen species (ROS) detection and western blot. At the sublethal concentration, andrographolide increased carboplatin sensitivity of Hep-2 cells by increasing carboplatin-induced apoptosis and inhibiting cell viability. Moreover, we found that andrographolide sensitized carboplatin mainly through the induction of ROS generation and apoptotic signaling. Taken together, these results indicate that andrographolide, along with carboplatin, synergistically inhibited cell proliferation and induced mitochondrial apoptosis of Hep-2 cells by increasing the intracellular ROS, regulating the mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3K/AKT) pathways, altering the BCL2/BAX ratio, and ultimately activating the cleavage of Caspase-3 and PARP. These results suggest that andrographolide sensitizes human laryngeal cancer cells to carboplatin-induced apoptosis by increasing ROS levels.

Elevated peripheral inflammatory markers are related with the recurrence and canceration of vocal fold leukoplakia.

OBJECTIVE: To evaluate the predictive value of preoperative peripheral inflammatory markers in patients with vocal fold leukoplakia. METHODS: A retrospective study was performed of the patients diagnosed with vocal fold leukoplakia and who accepted carbon dioxide (CO2) laser resection in our center in the last 10 years. We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) after collecting and analyzing the clinical, histopathological and laboratory data. The potential relation between blood indexes and clinical events as recurrence or canceration was evaluated. RESULTS: A total of 589 patients were involved, including 300 cases without recurrence (group A), 198 with recurrence but not canceration (group B) and 91 transformed into squamous cancer (group C). Baseline analysis of NLR, PLR, and MLR showed no difference among the three groups before the first surgery. But all the indexes significantly elevated in groups B (P < 0.001, < 0.001, 0.023, respectively) and C (P = 0.009, 0.004, 0.007, respectively) in the last operation. The receiver-operating curve (ROC) analysis showed NLR as a potential marker of canceration of leukoplakia (AUC = 0.837) and the cutoff value was 2.505. When regrouping with pathological outcomes, severe dysplasia and squamous cell carcinoma (SCC) groups both revealed a higher level of NLR, PLR, and MLR comparing to the no dysplasia, mild dysplasia, and moderate dysplasia groups. NLR, PLR, and MLR in high-risk group (moderate, severe dysplasia and carcinoma) also elevated comparing to low-risk group (no dysplasia, mild dysplasia) (P = 0.039, 0.011, 0.007, respectively). CONCLUSIONS: The peripheral inflammatory markers NLR, PLR, and MLR are closely connected with the development of vocal fold leukoplakia. NLR may be a potential marker to predict the poor outcomes (recurrence or canceration) of patients in first surgery.

A combined modality of carboplatin and photodynamic therapy suppresses epithelial-mesenchymal transition and matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in HEp-2 human laryngeal cancer cells via ROS-mediated inhibition of MEK/ERK signalling pathway.

Photodynamic therapy (PDT) has been developed as a promising treatment modality for laryngeal cancer. 9-Hydroxypheophorbide α (9-HPbD), a novel chlorophyll-derived photosensitizer, has a longer absorption wavelength, which increases the penetration of light to malignant tissues. Carboplatin (CBDCA), a second-generation platinum derivative, also has gained more popularity for the treatment of laryngeal cancer. Our previous studies have elucidated that 9-HPbD-PDT could inhibit the migration and invasion of HEp-2 cells. The objective of this study is to investigate the change of migration and invasion of HEp-2 cells induced by a combined modality of CBDCA and 9-HPbD-PDT in vitro. A wound healing assay, cell migration assay and Matrigel invasion assay were used to evaluate the cellular migration and invasion. Reactive oxygen species (ROS) and Western blots for epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and vimentin), MMPs (MMP-2 and MMP-9) and MEK/ERK signalling pathway were performed to investigate the possible mechanisms that may be involved. We observed that CBDCA and 9-HPbD-PDT administration synergistically inhibited the migration and invasion of HEp-2 cells. Moreover, the combined modality cooperatively repressed the EMT process and down-regulated expressions of MMP-2 and MMP-9 via ROS-mediated inhibition of phosphorylation in the MEK/ERK signalling pathway. Our results suggested that the combination of CBDCA and 9-HPbD-PDT might be a promising therapeutic strategy for laryngeal cancer metastasis.

A meta-analysis for the diagnostic accuracy of SelectMDx in prostate cancer.

To overview the diagnostic accuracy of SelectMDx for the detection of clinically significant prostate cancer and to review sources of methodologic variability. Four electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library were searched for eligible studies investigating the diagnostic value of SelectMDx compared with the gold standard. The pooled sensitivity, specificity, and positive and negative predictive values were calculated. Included studies were assessed according to the Standards for Quality Assessment of Diagnostic Accuracy Studies 2 tool. The review identified 14 relevant publications with 2579 patients. All reports constituted phase 1 biomarker studies. Pooled analysis of findings found an area under the receiver operating characteristic analysis curve of 70% [95% CI, 66%-74%], a sensitivity of 81% [95% CI, 69%-89%], and a specificity of 52% [95% CI, 41%-63%]. The positive likelihood ratio was 1.68, and the negative predictive value is 0.37. Factors that may influence variability in test results included the breath collection method, the patient's physiologic condition, the test environment, and the method of analysis. Considerable heterogeneity was observed among the studies owing to the difference in the sample size. SelectMDx appears to have moderate to good diagnostic accuracy in differentiating patients with clinically significant prostate cancer from people at high risk of developing prostate cancer. Higher-quality clinical studies assessing the diagnostic accuracy of SelectMDx for clinically significant cancer are still needed.

The prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

BACKGROUND: Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. MATERIALS AND METHODS: To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. RESULTS: A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87). CONCLUSION(S): The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.

Nonlinear Dynamic Analysis and Perturbation Measurement Used for Discriminating Pathological Voices and Their Correlations With Perceptual Evaluation.

OBJECTIVE: 1. To investigate the discriminatory and diagnostic power of nonlinear dynamic analysis measures concerning voices from normal, benign, and malignant voice disorders. 2. To study the correlations of nonlinear dynamic analysis measures with perceptual ratings to evaluate the reliability of the objective acoustic analysis in predicting severity of voice. METHOD: The perturbation analysis metrics used were Jitter%, Shimmer%, and signal-to-noise ratio. The nonlinear dynamic analysis metrics used were spectrum convergence ratio (SCR), nonlinear energy difference ratio (NEDR), and rate of divergence (ROD). Subjects were enrolled and divided into three groups based on laryngeal pathology: normal, benign, and malignant. Vowel sound and reading samples were recorded. Perceptual evaluation was applied to these voice samples to investigate correlations between metrics and auditory perception. RESULT: Each metric was capable of discriminating laryngeal pathology, except for SCR in the case of distinguishing between benign and malignant pathologies. Perturbation analysis parameters had a moderate ability to differentiate between normal and benign pathologies, but were unable to characterize malignant pathologies for certain diseases, such as Reinke's edema. All metrics significantly correlated with perceptual G scores. Nonlinear dynamic analysis was superior when applied to cases of severe dysphonia, where linear metrics such as Jitter% and Shimmer% tended to lose utility. NEDR and ROD were successful at differentiating between the different pathologies, whereas SCR could not discriminate between the benign and malignant groups. CONCLUSION: Perturbation and nonlinear dynamic analyses are comparable in their discriminating power with respect to normal and benign voices, and normal and malignant voices. The nonlinear dynamic analysis metrics NEDR and ROD may be superior in clinical settings with respect to discriminating voice pathology ranging from mild pathological voice to severe dysphonia, and with respect to discriminating benign and malignant voice. SCR was found unable to discriminate pathological voices.

KTP laser alone or combined with bleomycin for pharyngolaryngeal hemangioma: a lesion grade-based determination of prognosis.

BACKGROUND: No standard potassium titanyl phosphate (KTP) laser treatment strategy is available yet for pharyngolaryngeal hemangioma. OBJECTIVES: To explore the therapeutic effect of KTP laser, alone or combined with bleomycin injection, for pharyngolaryngeal hemangioma. MATERIAL AND METHODS: This observational study included patients with pharyngolaryngeal hemangioma treated between May 2016 and November 2021: KTP laser under local anesthesia, KTP laser under general anesthesia, or KTP laser combined with bleomycin injection under general anesthesia. RESULTS: A total of 60 patients were recruited, including 17, 19, and 24 patients with grade 1, 2, and 3 hemangiomas, respectively. A total of 21 patients underwent KTP laser under local anesthesia, 31 underwent KTP laser under general anesthesia, and 8 underwent KTP laser under general anesthesia combined with bleomycin. The cure rates were 100%, 89.5%, and 20.8% for grade 1, 2, and 3 lesions, respectively. The prognosis was significantly different among the grades of hemangioma (p < .001). CONCLUSION: KTP laser treatment might be an effective treatment for adult patients with pharyngolaryngeal hemangioma. The size of the hemangioma might be the major factor influencing the prognosis. The method of anesthesia and whether it was combined with bleomycin injection might not affect the prognosis.

Treatment of multiple myeloma based on autologous stem cell transplant: An overview of systematic reviews.

BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease. In recent years, several systematic reviews, and meta-analyses have been published on treatment protocols, including autologous stem cell transplantation for MM. METHODS: Web of Science, PubMed, Embase, and Cochrane Library were searched to systematically summarize the quality of the methodology and evidence of meta-analyses regarding treatment of MM including autologous stem cell transplantation. RESULTS: Total 11 meta-analyses were included. The preferred reporting items for systematic reviews and meta-analyses evaluation revealed that the quality of included reviews was affected by possible unevaluated bias between studies and the lack of protocol and registration. The AMSTAR2 scale indicated that the quality of the methodology of included reviews ranged from very low to moderate. The grading, assessment, development, and evaluation of recommendations evaluation showed that among the included outcome indicators, most of them are of low quality. CONCLUSION: This overview suggested that the combination of drugs has improved patient survival rates, efficacy and safety compared with the standard regimen. However, the strength of the evidence is uneven and due to methodological errors, the results should be interpreted with caution in order to provide a reference for further improvement of the study design. The methodological quality of the relevant meta-analysis needs to be further improved.

Impact of Obstructive Sleep Apnea on Health-Related Quality of Life in Patients With Partial Laryngectomy for Laryngeal Cancer.

Objectives: To evaluate the possible risk factors of obstructive sleep apnea (OSA) and its impact on the health-related quality of life (HRQoL) in patients with partial laryngectomy for laryngeal cancer. Methods: A cross-sectional method was used to carry out this study. Patients who underwent partial laryngectomy for laryngeal cancer completed overnight polygraphy (PG) home sleep tests and quality of life questionnaires. The Medical Outcome Study 36-item Short-Form Health Survey (SF-36) questionnaire was used to investigate the factors influencing HRQoL. Results: A total of 59 patients completed the PG tests and quality of life questionnaires, with 74.6% demonstrating evidence of OSA. There were significant differences in tumor area and neck dissection between OSA group and non-OSA groups. Based on sleep-related parameters, patients were divided into cluster 1 (n = 14) and cluster 2 (n = 45) using principal component analysis combined with K-means clustering. Two clusters had significantly different scores of body pain, general health, and health transition in SF-36 domains. Independent factors associated with general health were identified as tobacco use (OR = 4.716), alcohol use (OR = 3.193), and OSA-related condition (OR = 11.336). Conclusions: Larger tumor area and neck dissection might be associated with an increased risk for developing OSA in patients with partial laryngectomy for laryngeal cancer. OSA partially mediated the effect on physical health, including body pain, general health, and health transition. It is important to be aware of the potential impact of OSA on diminished HRQoL of these patients.

Treatment with adult glottic stenosis using CO2 laser surgery combined with self-made laryngeal dilator.

BACKGROUND/AIMS/OBJECTIVES: To investigate the treatment for adult glottic stenosis using CO2 laser surgery combined with a self-made laryngeal dilator. MATERIAL AND METHODS: A retrospective analysis was performed on 18 patients with glottic stenosis who were treated using CO2 laser surgery combined with a self-made laryngeal dilator in our hospital from January 2018 to December 2020. RESULTS: 4 cases were caused by trauma and one by laryngophthisis. Laryngeal stenosis occurred in 4 and 9 patients respectively after CO2 laser surgery and open partial laryngectomy. Of them, one patient underwent postoperative radiotherapy. All patients were treated through CO2 laser surgery combined with a self-made laryngeal dilator under general anesthesia. 3-6 months later, the dilator was removed. Inflammation, ulceration and granulation were observed surrounding the dilator. But these complications would be cured and respiration was not affected. Finally, four patients could not be extubated and the decannulation rate achieved 78%. All patients successfully decannulated could normally intake. 13 cases had good voice quality and only one patient pronounced hoarsely. CONCLUSIONS AND SIGNIFICANCE: It is demonstrated that the application of CO2 laser surgery combined with a laryngeal self-made dilator is feasible and effective for the treatment with adult glottic stenosis.

Chemical modification of curcumin increases its potency against hypopharyngeal carcinoma.

Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.

Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness.

Tonic signaling of chimeric antigen receptor (CAR), i.e., the spontaneous CAR activation in the absence of tumor antigen stimulation, is considered to be a pivotal event controlling CAR-T efficacy. However, the molecular mechanism underlying the spontaneous CAR signals remains elusive. Here, we unveil that positively charged patches (PCPs) on the surface of the CAR antigen-binding domain mediate CAR clustering and result in CAR tonic signaling. For CARs with high tonic signaling (e.g., GD2.CAR and CSPG4.CAR), reducing PCPs on CARs or boosting ionic strength in the culture medium during ex vivo CAR-T cell expansion minimizes spontaneous CAR activation and alleviates CAR-T cell exhaustion. In contrast, introducing PCPs into the CAR with weak tonic signaling, such as CD19.CAR, results in improved in vivo persistence and superior antitumor function. These results demonstrate that CAR tonic signaling is induced and maintained by PCP-mediated CAR clustering. Notably, the mutations we generated to alter the PCPs maintain the antigen-binding affinity and specificity of the CAR. Therefore, our findings suggest that the rational tuning of PCPs to optimize tonic signaling and in vivo fitness of CAR-T cells is a promising design strategy for the next-generation CAR.

Effect of low-level laser therapy on cochlear hair cell recovery after gentamicin-induced ototoxicity.

Cochlear hair cells are the sensory receptors of the auditory system. It is well established that antibiotic drugs such as gentamicin can damage hair cells and cause hearing loss. Rescuing hair cells after ototoxic injury is an important issue in hearing recovery. Although many studies have indicated a positive effect of low-level laser therapy (LLLT) on neural cell survival, there has been no study on the effects of LLLT on cochlear hair cells. Therefore, the aim of this study was to elucidate the effects of LLLT on hair cell survival following gentamicin exposure in organotypic cultures of the cochlea of rats. The cochlea cultures were then divided into a control group (n = 8), a laser-only group (n = 8), a gentamicin-only group (n = 8) and a gentamicin plus laser group (n = 7). The control cultures were allowed to grow continuously for 11 days. The laser-only cultures were irradiated with a laser with a wavelength of 810 nm at 8 mW/cm(2) for 60 min per day (0.48 J/cm(2)) for 6 days. The gentamicin groups were exposed to 1 mM gentamicin for 48 h and allowed to recover (gentamicin-only group) or allowed to recover with daily irradiation (gentamicin plus laser group). The hair cells in all groups were stained with FM1-43 and counted every 3 days. The number of hair cells was significantly larger in the gentamicin plus laser group than in the gentamicin-only group. The number of hair cells was larger in the laser-only group than in the control group, but the difference did not reach statistical significance. These results suggest that LLLT may promote hair cell survival following gentamicin damage in the cochlea. This is the first study in the literature that has demonstrated the beneficial effect of LLLT on the recovery of cochlear hair cells.

Characteristics of Depression Clinical Trials Registered on ClinicalTrials.gov.

Background: Mental disorders are among the leading causes of the global health-related burden, and depression is one of the most disabling mental disorders. The emergence of the COVID-19 pandemic has created an environment where many determinants of mental health are exacerbated. Many studies have been registered and conducted over the past 16 years, but how to choose the proper design for depression clinical trials remains the main concern. This study aimed to characterize the current status of global depression clinical trials registered on ClinicalTrials.gov. Methods: We examined all the trials registered on ClinicalTrials.gov from 2007 to 2021. Results: Overall, 7623 depression clinical trials were identified for analysis. Of those trials, 6402 (83.98%) were intervention trials and 1212 (15.90%) were observational trials. The majority of intervention types were behavioral (35.2%) and drug (28.55%), with very few procedures, dietary supplements, and diagnostic test studies. In addition, 55.53% of trials enrolled <100 participants. The proportions of trials registered in North America were higher than on other continents. Furthermore, the trials that involved only females (12.6%) were more than only males (0.87%) from 2019 to 2021. Conclusion: Depression clinical trials registered on ClinicalTrials.gov were dominated by small sample size trials, and there is a lack of trials related to COVID-19. The choice of study design is crucial, and properly designed trials can help improve study efficiency and reduce the likelihood of study failure. Given the increased number of RCT trials, the trial quality is gradually improving over the years. In addition, depression trials concentrating on children and older adults need more scientific attention. Further studies related to COVID-19 are needed, given the great damage that causes to people's physical and mental health.