Incidentally found parotid gland lesion in 18F-FDG PET/CT for staging evaluation of patients with hepatocellular carcinoma: remote possibility of metastatic tumor or second primary salivary gland malignancy.

OBJECTIVES: We primarily aimed to evaluate whether parotid incidental lesion (PIL) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging evaluation of patients with hepatocellular carcinoma (HCC) would represent a possibility of extrahepatic metastasis or second primary malignancy (SPM). Additionally, we explored the incidence of PIL in HCC patients and examined any associated risk factors. METHODS: We retrospectively analyzed patients with HCC who underwent 18F-FDG PET/CT at our institution from 2010 to 2022. The pathological findings of PILs in HCC patients were investigated for confirmatory identification of the risk of HCC metastasis or SPM in parotid gland. Healthy controls received 18F-FDG PET/CT for health screening were also enrolled to compare the incidence of PILs with HCC patients. Various parameters associated with patient demographics and characteristics of HCC were analyzed to find the related factors of PILs. RESULTS: A total of 17,674 patients with HCC and 2,090 healthy individuals who had undergone 18F-FDG PET/CT scans were enrolled in the analyses. Among the 54 HCC patients who underwent pathological confirmation for PILs, benign primary parotid tumor was most commonly observed (n = 43 [79.6%]); however, no malignant lesions were detected, including HCC metastasis. The incidence of PILs was higher in patients diagnosed with HCC compared with the control group (485 [2.7%] vs. 23 [1.1%], p = 0.002). Analysis for the risk factors for PILs revealed that patient age, sex, and positive viral markers were significantly associated with the incidence of PILs in patients with HCC (all p < 0.001). CONCLUSIONS: Our study demonstrates that PILs are more frequently identified in patients with HCC on 18F-FDG PET/CT. However, no malignant PIL, including extrahepatic metastasis of HCC, was identified. Therefore, the presence of PIL should not impede or delay the treatment process for patients with HCC. Additionally, we suggested that for future swift and straightforward differential diagnoses of PIL, the development of additional protocols within the PET/CT imaging could be beneficial.

Association between oral health and thyroid disorders: A population-based cross-sectional study.

OBJECTIVES: In this study, we aimed to determine the relationship between oral health status and thyroid dysfunction. METHODS: A population-based cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey (KNHNES) was performed. We investigated the association between oral health-related parameters and the prevalence of thyroid diseases. In addition, the relationship between oral health status and thyroid function test (TFT) results was analyzed. One-way analysis of variances or chi-square test was used for comparisons between oral health-related parameters and presence of thyroid diseases. Univariable and multivariable logistic regression analyses were conducted to evaluate the associations between participants' characteristics including oral health-related parameters and the abnormal results of TFTs. RESULTS: A total of 18,034 adults were surveyed. Histories of thyroid diseases were found to be more common in people who brushed their teeth frequently or used oral hygiene products. However, histories of periodontitis and community periodontal index (CPI) did not show significant associations with histories of thyroid diseases. Among 14,860 participants without history of thyroid disorders, people having higher CPI values demonstrated higher probabilities of abnormal TFTs (OR 1.381, 95% CI 1.241-1.537, p < .0001); however, statistical significance was not found after adjusting for the other variables. CONCLUSIONS: Our study demonstrated that good oral health-related behavior was associated with more frequent thyroid disease history. High CPI showed a significant association with TFT abnormalities; however, the significance of this association became lower when other variables such as age and sex were adjusted. Further studies will be needed to determine how the control of oral health-related conditions actually has a causal relationship with thyroid disease/dysfunction through prospective cohort studies.

Electro-Caloric Properties of BT/PZT Multilayer Thin Films Prepared by Sol-Gel Method.

In this study, Barium Titanate (BT)/Lead Zirconate Titanate (PZT) multilayer thin films were fabricated by the spin-coating method on Pt (200 nm)/Ti (10 nm) SiO2 (100 nm)/P-Si (100) substrates using BaTiO3 and Pb(Zr0.90Ti0.10)O3 metal alkoxide solutions. The coating and heating procedure was repeated several times to form the multilayer thin films. All of BT/PZT multilayer thin films show X-ray diffraction patterns typical to a polycrystalline perovskite structure and a uniform and void free grain microstructure. The thickness of the BT and PZT film by one-cycle of drying/sintering was approximately 50 nm and all of the films consisted of fine grains with a flat surface morphology. The electrocaloric properties of BT/PZT thin films were investigated by indirect estimation. The results showed that the temperature change ΔT can be calculated as a function of temperature using Maxwell's relation; the temperature change reaches a maximum value of ~1.85 °C at 135 °C under an applied electric field of 260 kV/cm.

Ultrasonography-guided core needle biopsy of cervical lymph nodes for diagnosing head and neck lymphoma compared with open surgical biopsy: Exploration for factors that shape diagnostic yield.

PURPOSE: This study was conducted to compare the diagnostic yields of Ultrasonography-guided core needle biopsy (USG-CNB) and open surgical biopsy (OSB) in head and neck (HN) lymphoma and to identify the factors that shape USG-CNB diagnostic yield. MATERIALS AND METHODS: All consecutive patients who were diagnosed with HN lymphoma in our hospital were analyzed. The frequencies with which these first-line procedures yielded a sample that permitted histological confirmation of lymphoma were determined. To identify the factors that shape the diagnostic yield of USG-CNB, the patients in whom USG-CNB was and was not sufficiently confirmatory were compared in terms of demographics, computed tomography (CT) and pathological findings. RESULTS: In total, 83 patients underwent USG-CNB (n = 26, 31.3%) or OSB (n = 57, 68.7%) for confirming lymphoma. USG-CNB yielded a fully sufficient diagnosis in 18 (69.2%) patients. By contrast, OSB yielded a confirmative diagnosis in 56 (98.2%) patients. Maximal standardized uptake value (SUVmax) of targeted LN on positron emission tomography-CT (PET-CT) in confirmatively diagnosed subjects was much higher than deferred counterparts (22.9 ±â€¯13.4 vs. 10.1 ±â€¯5.2, p = 0.017), however, there was no significant difference in other parameters associated with the first-line USG-CNB diagnostic success. CONCLUSIONS: First-line USG-CNB was less frequently successful than OSB for diagnosing HN lymphoma involving cervical LN. Mean SUVmax of LN on PET-CT in confirmatively diagnosed subjects was higher than deferred counterparts on USG-CNB.

Clinical implications of nonspecific pulmonary nodules identified during the initial evaluation of patients with head and neck squamous cell carcinoma.

OBJECTIVE: We aimed to identify the clinical implications of nonspecific pulmonary nodules (NPNs) detected in the initial staging workup for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Medical records of patients who had been diagnosed and treated in our hospital were retrospectively analysed. After definite treatment, changes of NPNs detected on initial evaluation were monitored via serial chest computed tomography. The associations between NPNs and the clinicopathological characteristics of primary HNSCC were evaluated. Survival analyses were performed according to the presence of NPNs. RESULTS: The study consisted of 158 (49.4%) patients without NPNs and 162 (50.6%) patients with NPNs. The cumulative incidence of probabilities of pulmonary malignancy (PM) development at 2 years after treatment were 9.0% and 6.2% in NPN-negative and NPN-positive patients, respectively. Overall and PM-free survival rates were not significantly different according to NPN status. Cervical lymph node (LN) involvement and a platelet-lymphocyte ratio (PLR) ≥126 increased the risk of PMs (both P <0.05). CONCLUSIONS: NPNs detected in the initial evaluation of patients with HNSCC did not predict the risk of pulmonary malignancies. Cervical LN involvement and PLR ≥126 may be independent prognostic factors affecting PM-free survival regardless of NPN status. KEY POINTS: • We aimed to identify the clinical implications of nonspecific pulmonary nodules (NPNs). • NPNs in head and neck cancer patients do not lead to pulmonary malignancies (PMs). • NPNs are not associated with overall or PM-free survival (PMFS). • Cervical lymph node involvement is an independent prognostic factor affecting PMFS. • Platelet-lymphocyte ratio ≥126 is another predictor of PMFS regardless of NPN presence.

An Introduction to a Head and Neck Cancer-Specific Frailty Index and Its Clinical Implications in Elderly Patients: A Prospective Observational Study Focusing on Respiratory and Swallowing Functions.

INTRODUCTION: Frailty refers to a decreased physiologic reserve in geriatric patients and its importance in terms of treatment planning and outcome prediction has been emphasized in oncologic practices for older patients with cancer. We investigated the clinical implications of a head and neck cancer (HNC)-specific frailty index suggested by prospective clinical and functional evaluations of HNC patients. MATERIALS AND METHODS: We analyzed data on 165 elderly patients with HNC who were prospectively enrolled in our hospital from 2010 to 2013. Pretreatment functional evaluations were performed according to all comprehensive geriatric assessment (CGA) domains. We additionally evaluated the patients' respiratory and swallowing functions using pulmonary function tests, voice handicap index (VHI), MD Anderson Dysphagia Inventory (MDADI), and other associated tests. Factors affecting the 2-year morbidity and mortality were also analyzed. RESULTS: Respiratory and swallowing problems were major causes of 2-year morbidity. Pretreatment performance status, VHI ≥8, MDADI <70, dental problems, and chemotherapy were significantly associated with early morbidity and mortality (all p < .05). CGA-assessed frailty was found in 72 patients (43.6%) and was significantly associated with 2-year mortality (p = .027) but not with morbidity (p = .716). The high-risk group according to our new HNC-specific frailty index that included functional evaluations of respiration and swallowing showed significantly higher 2-year morbidity (p = .043) and mortality (p < .001). CONCLUSION: Pretreatment functional disabilities related to respiration and swallowing were significantly associated with early morbidity and mortality. The suggested index would be more useful for assessing frailty in elderly HNC patients. IMPLICATIONS FOR PRACTICE: This study is the first report in terms of suggesting a new frailty index focusing on respiratory and swallowing functions in elderly patients with head and neck cancer. This study shows that functional disabilities associated with respiration and swallowing significantly affected early morbidity and mortality in these elderly patients. The head and neck cancer-specific frailty index described in this report, which includes functional evaluations of respiration and swallowing, significantly predicted both early morbidity and mortality.

Clinical significance of three-dimensional measurement of tumour thickness on magnetic resonance imaging in patients with oral tongue squamous cell carcinoma.

OBJECTIVES: To identify the clinical significance of primary tumour thickness (TT) and its direction in patients with oral tongue squamous cell carcinoma (OTSCC), we measured TT in all axial/coronal/sagittal views on magnetic resonance imaging (MRI) and evaluated their meaning. METHODS: A total of 53 OTSCC patients were analysed who had undergone preoperative three-dimensional MRI and had been surgically treated. TT measured on axial (mediolateral direction), coronal (superoinferior direction), and sagittal (anteroposterior direction) views was compared to that in pathologic specimens. The association between TT on MRI and other pathologic parameters was also evaluated. RESULTS: TT on MRI in each plane showed relatively high concordance rates with the histological measurements. TT in all three planes was significantly correlated with lymph node (LN) metastasis. Occult LN metastasis was found in 15 of 39 (38.5%) patients, and the cutoff value of TT in axial/coronal/sagittal MRI predicting occult LN metastasis was 6.7 mm, 7.2 mm, and 12.3 mm, respectively. TT on MRI did not show any significant association with recurrence and survival. CONCLUSIONS: TT on MRI in all three planes showed relatively high coincidence with TT on histopathology and presented a potential cut-off value as a predictive indicator for occult LN metastasis. KEY POINTS: Three-dimensional measurement of tumour thickness (TT) is important for oral cancer treatment. Magnetic resonance imaging (MRI) is a useful diagnostic tool for oral cancer. TT on MRI has a high coincidence with TT on histopathology. TT on MRI is a predictive marker for occult lymph node metastasis.

Effect of metformin on progression of head and neck cancers, occurrence of second primary cancers, and cause-specific survival.

BACKGROUND: This study aimed to investigate the effect of metformin on progression of head and neck cancers, occurrence of second primary cancers, and cause-specific survival. METHODS: This study analyzed a retrospective cohort of 1,151 consecutive patients with head and neck squamous cell carcinoma who were treated at our hospital. Patients were divided into three groups: nondiabetic, nonmetformin, and metformin. Clinical characteristics, recurrence of index head and neck cancer, occurrence of second primary cancer, and survival were compared among the different groups. RESULTS: Of 1,151 patients, 99 (8.6%) were included in the metformin group, 79 (6.8%) were in the nonmetformin group, and 973 (84.5%) were in the nondiabetic group. Diabetic status and metformin exposure had no significant impact on index head and neck cancer recurrence or second primary cancer development (p > .2). The nonmetformin group showed relatively lower overall (p = .017) and cancer-specific (p = .054) survival rates than the other groups in univariate analyses, but these results were not confirmed in multivariate analyses. CONCLUSION: Metformin use did not show beneficial effects on index tumor progression, second primary cancer occurrence, and cause-specific survival in patients with head and neck cancer compared with nonmetformin users and nondiabetic patients.

The Impact of Infectious Mononucleosis History on the Risk of Developing Lymphoma and Nasopharyngeal Carcinoma: A Retrospective Large-Scale Cohort Study Using National Health Insurance Data in South Korea.

PURPOSE: This study aimed to assess the long-term risks associated with a history of infectious mononucleosis (IM), primarily caused by the Epstein-Barr virus (EBV). Specifically analyzing the potential increase in developing nasopharyngeal cancer (NPC) and lymphoma in patients with a history of IM and exploring the prevalence of other EBV-associated conditions. MATERIALS AND METHODS: The Korean National Health Insurance Service (NHIS) database was utilized for a retrospective analysis, covering data from 2002 to 2021. A total of 25,582 IM patients and controls were included, with 1:1 propensity score matching. The study monitored outcomes, including lymphoma, NPC, gastric cancer, multiple sclerosis, and all-cause mortality. RESULTS: Patients with a history of IM demonstrated a significantly higher incidence of lymphoma (hazard ratio [HR], 5.320; 95% confidence interval [CI], 3.208 to 8.820; p < 0.001) and NPC (HR, 7.116; 95% CI, 1.617 to 31.314; p=0.009) during the follow-up period compared with the control group. Additionally, the IM group showed an increased rate of all-cause mortality (HR, 2.225; 95% CI, 1.858 to 2.663; p < 0.001). CONCLUSION: This study suggests that individuals with a history of IM have an elevated risk of developing lymphoma and NPC in South Korea, emphasizing the importance of vigilant follow-up and monitoring. The results advocate for heightened awareness and potential national monitoring policies to address the long-term health implications of EBV infection and to implement preventive measures.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Seoul, Korea.

BACKGROUND: The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during the endemic phase may vary from that during the previous pandemic phase. We evaluated the risk of infection in a general population with laboratory-confirmed coronavirus disease 2019 (COVID-19) in a community setting in Korea. MATERIALS AND METHODS: This study included 1,286 individuals who had been in contact with an index COVID-19 case between January 24, 2020, and June 30, 2022. Variables such as age, sex, nationality, place of contact, level of contact, the status of exposed cases, period, and level of mask-wearing were assessed. RESULTS: Among 1,286 participants, 132 (10.30%) were confirmed to have COVID-19. With increasing age, the risk of the exposed persons contracting COVID-19 from index cases tended to increase (P <0.001), especially for people in their 70s (odds ratio, 1.24; 95% confidence interval, 1.11-1.40; P <0.001). We found an increasing trend in the risk of a COVID-19 exposed case becoming a secondary infection case (P <0.001) in long-term care facilities where the attack rate was high. CONCLUSION: The risk of COVID-19 transmission is high in long-term care facilities where many older adults reside. Intensive management of facilities at risk of infection and strict mask-wearing of confirmed COVID-19 cases are necessary to prevent the risk of COVID-19 infection.

Additional injection laryngoplasty as a salvage treatment for unilateral vocal fold paralysis.

OBJECTIVES: Injection laryngoplasty (IL) has been widely used as an initial treatment option for unilateral vocal fold paralysis (UVFP). An additional (second) IL is considered a salvage treatment for unsatisfactory outcomes of initial IL resulting from inadequate injection or early resorption of the injection material. This study aims to evaluate the efficacy of additional IL, distinguishing between "salvage" (within 4 months) and "repeated" injections (beyond 4 months), and to analyze prognostic factors for successful outcomes. METHODS: This retrospective study involved patients who received IL at Asan Medical Center from January 2014 to December 2020. Voice parameters were collected after each procedure, and those who conducted the statistical analysis were blinded to the study subjects. Among the 65 patients who underwent additional IL, 51 patients were enrolled in this study. Postinjection grade, roughness, breathiness, asthenia, strain (GRBAS) scales were used to determine satisfactory treatment outcomes. Success of the additional IL was defined as a postinjection grade of dysphonia score of 0 or 1, with a reduction in grade compared with the preinjection grade. RESULTS: The mean age of the patients was 61.6 years. Out of a total of 51 patients, 37 were men participating in the study. The odds ratio represents the likelihood of success in the second IL. Improved voice outcome after the additional IL was maintained in 23 (45%) patients. Compared with the failure group, the success group had a longer injection time interval between the initial and additional injection (9.1 vs. 7.4 months, respectively, p = 0.010). The success group had a higher proportion of patients with injection intervals >6 months (73.9% vs. 42.9%, p = 0.026). Logistic regression analysis revealed an injection interval >6 months had an odds ratio of 0.265 (confidence interval: 0.080-0.874, p = 0.029). CONCLUSIONS: Additional injections would benefit the patients whose voice outcomes are maintained for a longer period (>6 months) after the first injection.

Clinical implication of neck dissection for metastatic lymph nodes originating from non-head and neck regions.

BACKGROUND: Cervical lymph node metastasis (CLNM) from remote primary sites is rare in head and neck cancer. The efficacy of neck dissection is still being investigated for therapeutic benefits of local management in oligometastasis from non-head and neck cancer. OBJECTIVES: To evaluate the clinical efficacy of neck dissection (ND) in CLNM from distant primary cancers and identify factors contributing to improved survival. MATERIALS AND METHODS: This retrospective case-control study enrolled patients who underwent ND for CLNM from distant primary cancer at Asan Medical Centre between January 2010 and December 2020. We analysed overall survival and association between clinical covariate and survival. RESULTS: The study included 31 (14 males, 17 females) among 114 patients. Ovarian cancer was the most common primary malignancy (32.3%). Patients with fewer than three metastatic lymph nodes, without extranodal extension and with adjuvant therapy after surgery had better survival rates. CONCLUSION AND SIGNIFICANCE: In patients with CLNM from a distant primary cancer, ND is beneficial as local treatment. And adequate selection of patients for ND is pivotal to improve prognosis.

Novel Personalized Cancer Vaccine Using Tumor Extracellular Vesicles with Attenuated Tumorigenicity and Enhanced Immunogenicity.

Cancer vaccines offer a promising avenue in cancer immunotherapy by inducing systemic, tumor-specific immune responses. Tumor extracellular vesicles (TEVs) are nanoparticles naturally laden with tumor antigens, making them appealing for vaccine development. However, their inherent malignant properties from the original tumor cells limit their direct therapeutic use. This study introduces a novel approach to repurpose TEVs as potent personalized cancer vaccines. The study shows that inhibition of both YAP and autophagy not only diminishes the malignancy-associated traits of TEVs but also enhances their immunogenic attributes by enriching their load of tumor antigens and adjuvants. These revamped TEVs, termed attenuated yet immunogenically potentiated TEVs (AI-TEVs), showcase potential in inhibiting tumor growth, both as a preventive measure and a possible treatment for recurrent cancers. They prompt a tumor-specific and enduring immune memory. In addition, by showing that AI-TEVs can counteract cancer growth in a personalized vaccine approach, a potential strategy is presented for developing postoperative cancer immunotherapy that's enduring and tailored to individual patients.

Novel insights into paclitaxel's role on tumor-associated macrophages in enhancing PD-1 blockade in breast cancer treatment.

BACKGROUND: Triple-negative breast cancer (TNBC) poses unique challenges due to its complex nature and the need for more effective treatments. Recent studies showed encouraging outcomes from combining paclitaxel (PTX) with programmed cell death protein-1 (PD-1) blockade in treating TNBC, although the exact mechanisms behind the improved results are unclear. METHODS: We employed an integrated approach, analyzing spatial transcriptomics and single-cell RNA sequencing data from TNBC patients to understand why the combination of PTX and PD-1 blockade showed better response in TNBC patients. We focused on toll-like receptor 4 (TLR4), a receptor of PTX, and its role in modulating the cross-presentation signaling pathways in tumor-associated macrophages (TAMs) within the tumor microenvironment. Leveraging insights obtained from patient-derived data, we conducted in vitro experiments using immunosuppressive bone marrow-derived macrophages (iBMDMs) to validate if PTX could augment the cross-presentation and phagocytosis activities. Subsequently, we extended our study to an in vivo murine model of TNBC to ascertain the effects of PTX on the cross-presentation capabilities of TAMs and its downstream impact on CD8+ T cell-mediated immune responses. RESULTS: Data analysis from TNBC patients revealed that the activation of TLR4 and cross-presentation signaling pathways are crucial for the antitumor efficacy of PTX. In vitro studies showed that PTX treatment enhances the cross-presentation ability of iBMDMs. In vivo experiments demonstrated that PTX activates TLR4-dependent cross-presentation in TAMs, improving CD8+ T cell-mediated antitumor responses. The efficacy of PTX in promoting antitumor immunity was elicited when combined with PD-1 blockade, suggesting a complementary interaction. CONCLUSIONS: This study reveals how PTX boosts the effectiveness of PD-1 inhibitors in treating TNBC. We found that PTX activates TLR4 signaling in TAMs. This activation enhances their ability to present antigens, thereby boosting CD8+ T cell antitumor responses. These findings not only shed light on PTX's immunomodulatory role in TNBC but also underscore the potential of targeting TAMs' antigen presentation capabilities in immunotherapy approaches.

Small Extracellular Vesicles as a New Class of Medicines.

Extracellular vesicles (EVs) are nanovesicles that are naturally released from cells in a lipid bilayer-bound form. A subset population with a size of 200 nm, small EVs (sEVs), is enticing in many ways. Initially perceived as mere waste receptacles, sEVs have revealed other biological functions, such as cell-to-cell signal transduction and communication. Besides their notable biological functions, sEVs have profound advantages as future drug modalities: (i) excellent biocompatibility, (ii) high stability, and (iii) the potential to carry undruggable macromolecules as cargo. Indeed, many biopharmaceutical companies are utilizing sEVs, not only as diagnostic biomarkers but as therapeutic drugs. However, as all inchoate fields are challenging, there are limitations and hindrances in the clinical translation of sEV therapeutics. In this review, we summarize different types of sEV therapeutics, future improvements, and current strategies in large-scale production.

Prognostic significance of 25-hydroxyvitamin D levels in patients with peripheral T-cell lymphoma.

Vitamin D insufficiency has been linked to unfavourable outcomes in diverse malignancies. However, the prognostic significance of vitamin D levels in peripheral T-cell lymphoma (PTCL) remains unclear. In this study, we thus aimed to assess the prognostic relevance of 25-hydroxyvitamin D [25(OH)D] levels in patients newly diagnosed with PTCL. The analysis included 144 patients with PTCL treated from March 2015 to May 2020. The median 25(OH)D level was 12.2 (1.7-48.8) ng/mL, and 59 (41%) patients had vitamin D deficiency. Patients with vitamin D deficiency demonstrated significantly worse event-free survival (EFS) and overall survival (OS). In the multivariate analysis, vitamin D was independently associated with OS, with a hazard ratio of 1.66 (95% confidence interval, 1.05-2.63, p = 0.030). These findings suggest that vitamin D deficiency significantly correlates with poor survival outcomes in patients with PTCL.

Guidelines for the Use of Botulinum Toxin in Otolaryngology From the Korean Society of Laryngology, Phoniatrics and Logopedics Guideline Task Force.

The Korean Society of Laryngology, Phoniatrics and Logopedics created a task force to establish clinical practice guidelines for the use of botulinum toxin (BT) in otolaryngology. We selected 10 disease categories: spasmodic dysphonia, essential vocal tremor, vocal fold granuloma, bilateral vocal fold paralysis, Frey's syndrome, sialocele, sialorrhea, cricopharyngeal dysfunction, chronic sialadenitis, and first bite syndrome. To retrieve all relevant papers, we searched the CORE databases with predefined search strategies, including Medline (PubMed), Embase, the Cochrane Library, and KoreaMed. The committee reported 13 final recommendations with detailed evidence profiles. The guidelines are primarily aimed at all clinicians applying BT to the head and neck area. In addition, the guidelines aim to promote an improved understanding of the safe and effective use of BT by policymakers and counselors, as well as in patients scheduled to receive BT injections.

Coprevalence of Presbycusis and Its Effect on Outcome of Voice Therapy in Patients With Presbyphonia.

OBJECTIVE: To identify the coprevalence of presbycusis and presbycusis and analyze the effect of presbycusis on compliance and result of voice therapy in presbycusis patients. METHODS: This cross-sectional, prospective cohort study initially screened patients aged ≥65 years who visited our hospital from February 2019 to January 2020. Unaided pure tone audiometry was performed in these subjects to determine the presence of presbycusis. Perceptual voice assessment by an examiner was conducted for screening of presbycusis, and its diagnosis was confirmed through the voice handicap index-10 (VHI-10) questionnaire and a laryngoscopic exam. Patients with presbycusis underwent voice therapy and were assessed for their compliance and outcomes of the treatment according to the coexistence of presbycusis. RESULTS: Among the 221 patients, presbycusis and presbycusis were diagnosed in 125 (56.6%) and 110 (49.8%) patients, respectively. The copresence of these two disorders were identified in 87 (39.4%) patients, and there was a significant correlation between presbycusis and presbycusis. The effects of voice therapy were examined in the consecutive 40 patients who were diagnosed with presbycusis. There were 21 patients without presbycusis and 19 patients with presbycusis. The average pretreatment voice handicap index-10 score was significantly higher in presbycusis patients; there was no significant difference in the incidence of dropout from voice therapy between the groups. The patients without presbycusis showed a significant improvement in the functional communication measurement (FCM) level and maximum phonation time (MPT) compared with those of patients with presbycusis after voice therapy. CONCLUSIONS: Presbyphonia and presbycusis coexisted in many elderly people. The improvement in the FCM level and MPT after voice therapy was relatively low if patients with presbycusis accompanied by presbycusis. The copresence of presbycusis did not significantly affect compliance with voice therapy in the patients.

Advantage of extracellular vesicles in hindering the CD47 signal for cancer immunotherapy.

The cluster of differentiation 47 (CD47) protein is abundantly expressed on various malignant cells and suppresses the phagocytic function of macrophages and dendritic cells. High CD47 expression levels are correlated with poor cancer survival. Antagonizing CD47 antibodies with potent antitumor effects have been developed in clinical trials, but have critical side effects, inducing anemia and thrombocytopenia. To develop a safe and potent CD47 blockade, we designed extracellular vesicles (EVs) harboring signal regulatory protein alpha (SIPRα)-EV-SIRPα (EVs that express SIPRα). EV-SIRPα showed minimal toxic effects on hematologic parameters and utilized RBCs as delivery vehicles to tumors rather than inducing anemia. EV-SIRPα inhibited ligation of residual CD47 molecules, which attribute to the EV-endocytosis-mediated CD47 depletion and steric hindrance of EV. In an immunologically cold tumor model, EV-SIRPα induced tumor-specific T-cell-mediated antitumor effects. When directly administered to the accessible lesions, EV-SIRPα monotherapy elicited an abscopal effect in the B16F10 tumor model by increasing immune cell infiltration and CD8+-mediated immunity against non-treated tumors. The combinational approach by loading doxorubicin into the EV-SIRPα dramatically reduced the tumor burden and led to 80% complete remission rate. Thus, a potent EV-based CD47 blockade that is hematologically safe, has efficient signaling blocking efficacy, and has systemic antitumor immunity against cancer is recommended.

The right Timing, right combination, right sequence, and right delivery for Cancer immunotherapy.

Cancer immunotherapy (CI) represented by immune checkpoint inhibitors (ICIs) presents a new paradigm for cancer treatment. However, the types of cancer that attain a therapeutic benefit from ICIs are limited, and the efficacy of these treatments does not meet expectations. To date, research on ICIs has mainly focused on identifying biomarkers and patient characteristics that can enhance the therapeutic effect on tumors. However, studies on combinational strategies for CI are being actively conducted to overcome the resistance to ICI treatment. Moreover, it has been confirmed that dramatic anticancer effects are achieved through "neoadjuvant" immunotherapy with ICIs in treatment-naïve cancer patients; consequently, it has become necessary to consider how to best apply cancer immunotherapies for patients, even with respect to their tumor stages. In this review, we sought to discuss the right timing of ICI treatment in consideration of the progression of cancer with a changing tumor-immune microenvironment. Furthermore, we investigated which types of combinational treatments and their corresponding sequences of administration could optimize the therapeutic effect of ICIs to expand the applicable target of ICIs and increase their therapeutic efficacy. Finally, we discussed several delivery pathways and methods that can maximize the effect of ICIs.