Difficulties of Preoperative Diagnosis of Cribriform Morular Thyroid Carcinoma.

Background: Cribriform morular thyroid carcinoma has been recently renamed in the 2022 WHO classification as a thyroid tumor of uncertain histogenesis. The epidemiologic, pathological, and pathophysiological characteristics distinguish it from papillary thyroid carcinoma (PTC). Preoperative genetic testing plays a role in facilitating the differential diagnosis. Methods: This report presents a confirmed case of cribriform morular thyroid carcinoma. Initially, fine-needle aspiration cytology suggested a diagnosis of PTC. However, a genetic analysis did not reveal the typical mutations associated with follicular-cell-derived neoplasms. Results: A 31-year-old woman was found to have a thyroid nodule at the left lobe measuring 11.8 × 10.2 × 12.4 mm. Ultrasonography indicated a hypoechoic, solid nodule with regular margins. Cytology revealed a papillary structure of tall cells, leading to a PTC diagnosis. Nevertheless, the genetic analysis failed to detect mutations such as BRAF V600E, NRAS Q61R, NRAS Q61K, HRAS Q61R, or HRAS Q61K mutation or the fusion of CCDC6-RET, NCOA4-RET, PAX8-PPARG, ETV6-NTRK3, TPM3-NTRK1, IRF2BP2-NTRK1, or SQSTM1-NTRK1 in the aspirated follicular cells. The patient subsequently underwent total thyroidectomy with central lymph node dissection. Pathological examination revealed a cribriform pattern of spindle-shaped cells with morular areas. Immunohistochemical staining showed positive results for ß-catenin and TTF-1, except in the morular regions, and negative results for PAX8, thyroglobulin, and BRAF (clone VE1). The diagnosis was confirmed to be cribriform morular thyroid carcinoma. Conclusion: Significant cytological similarity exists between PTC and cribriform morular thyroid carcinoma. Preoperative genetic analysis is important to differentiate these two diseases. Cribriform morular thyroid carcinoma can be differentiated from common follicular-cell-derived tumors by the absence of typical mutations; the presence of nuclear and cytoplasmic expressions of ß-catenin; the presence of TTF-1, except in morular areas; and the absence of thyroglobulin.

Detection of trichomonads in patients with lung cancer and transcription analysis on the response of human pulmonary epithelial cells to Trichomonas tenax invasion.

INTRODUCTION: Lung cancer is one of the most prevalent malignancies worldwide. Substantial research has illuminated the intricate interplay between microorganisms and human health, revealing their role in disease regulation. Trichomonads is a flagellated protozoan in the human cavity and have been previously identified as a pathogen associated with pneumonia, contributing to tissue chronic inflammation and carcinogenesis. METHODS: Nested polymerase chain reaction methods were employed to scrutinize the prevalence of trichomonads in the bronchovesicular fluid of patients diagnosed with lung cancer. Subsequently, the influence of Trichomonas tenax invasion on lung cancer cells was elucidated through proliferation assays, migration assays, and transcription analysis. RESULTS: Bronchoalveolar fluid samples from lung cancer patients yielded positive nested PCR results for eight out of twenty-seven samples. Seven of these samples were identified as Trichomonas tenax, while one was identified as Tetratrichomonas spp. Our findings revealed a significant upregulation of pathways associated with carcinogenesis, including cellular proliferation, migration, and drug resistance, in response to T. tenax invasion. CONCLUSIONS: This study underscores the importance of recognizing the presence of trichomonads and the influence of T. tenax invasion on host responses to respiratory diseases. The identified pathways implicated in cancer development may pave the way for developing targeted treatment strategies for pulmonary diseases. These findings hold promise for informing and improving the precision of therapeutic interventions in the context of pulmonary ailments.

Healthcare Service Providers' Perspectives on Sociocultural Aspects Affecting Weight Management Activities Amongst People with Obesity in Taiwan-A Qualitative Study.

The prevalence of obesity and morbid obesity in Taiwan has risen sharply in recent decades, as in other parts of the world, necessitating urgent action to prevent and curb its detrimental effects. Asian populations are susceptible to the repercussions of obesity at a lower body weight. A higher BMI is associated with more frequent outpatient visits, in-hospital admissions, higher medical costs, and a lower quality of life. However, effective weight management approaches are unlikely to be maintained in the long term without assimilation into daily lifestyle practices. This qualitative study, based on semi-structured interviews with 14 doctors, dieticians, and nurses who work to control the weight of people with obesity, explored and identified multilevel barriers in the context of daily life to improve the efficacy and execution of weight management strategies. They considered diets, physical activity, and sleep as key weight management activities. The cultural and psychosocial aspects of daily life were observed to have an impact upon weight management, particularly family conflicts due to cultural dynamics and socially and culturally reinforced food practices. To improve population weight, less-recognised aspects need to be addressed alongside the inclusion of mental health specialists in weight management protocols and policy interventions to minimise obesogenic practices and create environments conducive to weight management.

Vascular Calcification Heterogeneity from Bench to Bedside: Implications for Manifestations, Pathogenesis, and Treatment Considerations.

Vascular calcification (VC) is the ectopic deposition of calcium-containing apatite within vascular walls, exhibiting a high prevalence in older adults, and those with diabetes or chronic kidney disease. VC is a subclinical cardiovascular risk trait that increases mortality and functional deterioration. However, effective treatments for VC remain largely unavailable despite multiple attempts. Part of this therapeutic nihilism results from the failure to appreciate the diversity of VC as a pathological complex, with unforeseeable variations in morphology, risk associates, and anatomical and molecular pathogenesis, affecting clinical management strategies. VC should not be considered a homogeneous pathology because accumulating evidence refutes its conceptual and content uniformity. Here, we summarize the pathophysiological sources of VC heterogeneity from the intersecting pathways and networks of cellular, subcellular, and molecular crosstalk. Part of these pathological connections are synergistic or mutually antagonistic. We then introduce clinical implications related to the VC heterogeneity concept. Even within the same individual, a specific artery may exhibit the strongest tendency for calcification compared with other arteries. The prognostic value of VC may only be detectable with a detailed characterization of calcification morphology and features. VC heterogeneity is also evident, as VC risk factors vary between different arterial segments and layers. Therefore, diagnostic and screening strategies for VC may be improved based on VC heterogeneity, including the use of radiomics. Finally, pursuing a homogeneous treatment strategy is discouraged and we suggest a more rational approach by diversifying the treatment spectrum. This may greatly benefit subsequent efforts to identify effective VC therapeutics.

The high-density lipoprotein cholesterol (HDL-C)-concentration-dependent association between anti-inflammatory capacity and sepsis: A single-center cross-sectional study.

INTRODUCTION: Known to have pleiotropic functions, high-density lipoprotein (HDL) helps to regulate systemic inflammation during sepsis. As preserving HDL-C level is a promising therapeutic strategy for sepsis, the interaction between HDL and sepsis worth further investigation. This study aimed to determine the impact of sepsis on HDL's anti-inflammatory capacity and explore its correlations with disease severity and laboratory parameters. METHODS AND MATERIALS: We enrolled 80 septic subjects admitted to the intensive care unit and 50 controls admitted for scheduled coronary angiography in this cross-sectional study. We used apolipoprotein-B depleted (apoB-depleted) plasma to measure the anti-inflammatory capacity of HDL-C. ApoB-depleted plasma's anti-inflammatory capacity is defined as its ability to suppress tumor necrosis factor-α-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical-vein endothelial cells. A subgroup analysis was conducted to investigate in septic subjects according to disease severity. RESULTS: ApoB-depleted plasma's anti-inflammatory capacity was reduced in septic subjects relative to controls (VCAM-1 mRNA fold change: 50.1% vs. 35.5%; p < 0.0001). The impairment was more pronounced in septic subjects with than in those without septic shock (55.8% vs. 45.3%, p = 0.0022). Both associations were rendered non-significant with the adjustment for the HDL-C level. In sepsis patients, VCAM-1 mRNA fold change correlated with the SOFA score (Spearman's r = 0.231, p = 0.039), lactate level (r = 0.297, p = 0.0074), HDL-C level (r = -0.370, p = 0.0007), and inflammatory markers (C-reactive protein level: r = 0.441, p <0.0001; white blood cell: r = 0.353, p = 0.0013). CONCLUSION: ApoB-depleted plasma's anti-inflammatory capacity is reduced in sepsis patients and this association depends of HDL-C concentration. In sepsis patients, this capacity correlates with disease severity and inflammatory markers. These findings explain the prognostic role of the HDL-C level in sepsis and indirectly support the rationale for targeting HDL-C as sepsis treatment.

The effects of pterygomaxillary disjunction in surgically assisted rapid maxillary expansion: A systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the expansive effects of pterygomaxillary disjunction (PMD) in surgically assisted rapid maxillary expansion (SARME) surgery using a meta-analysis approach. MATERIALS AND METHODS: The study conducted a comprehensive literature search across five databases: PubMed, Scopus, Medline, Embase, and Cochrane, adhering to the PRISMA 2020 guidelines. Dental alterations were assessed using either cone-beam computed tomography (CBCT) or dental casts, while skeletal changes were exclusively measured from CBCT scans. We analysed the dentoskeletal changes between PMD +/- groups and conducted a within-group comparison. The primary focus of the results was on the mean differences observed in pre- and post-operative measurements. RESULTS: Dental expansion was larger in the PMD+ group but not statistically significant. Skeletal expansion showed a significantly larger expansion in the posterior region in the PMD+ group (P = .033). Without PMD, anterior palatal expansion was significantly larger (P = .03), and the buccal tipping of posterior teeth was also significantly larger (P = .011) to achieve acceptable dental expansion outcomes. CONCLUSIONS: Both PMD +/- groups of SARME surgery can achieve satisfactory dental expansion outcomes. However, bone expansion and tooth inclination are also important factors that influence orthodontic treatment and post-expansion stability. By reducing the bony resistance with PMD, larger posterior palatal expansion and more parallel bony expansion are observed. In contrast, without PMD, there is smaller palatal expansion and greater tooth inclination in the posterior region. This could potentially lead to compromised periodontal conditions following expansion.

Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies.

Type 2 diabetes mellitus (T2DM) presents a challenge for individuals today, affecting their health and life quality. Besides its known complications, T2DM has been found to contribute to bone/mineral abnormalities, thereby increasing the vulnerability to bone fragility/fractures. However, there is still a need for appropriate diagnostic approaches and targeted medications to address T2DM-associated bone diseases. This study aims to investigate the relationship between changes in gut microbiota, T2DM, and osteoporosis. To explore this, a T2DM rat model was induced by combining a high-fat diet and low-dose streptozotocin treatment. Our findings reveal that T2DM rats have lower bone mass and reduced levels of bone turnover markers compared to control rats. We also observe significant alterations in gut microbiota in T2DM rats, characterized by a higher relative abundance of Firmicutes (F) and Proteobacteria (P), but a lower relative abundance of Bacteroidetes (B) at the phylum level. Further analysis indicates a correlation between the F/B ratio and bone turnover levels, as well as between the B/P ratio and HbA1c levels. Additionally, at the genus level, we observe an inverse correlation in the relative abundance of Lachnospiraceae. These findings show promise for the development of new strategies to diagnose and treat T2DM-associated bone diseases.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines.

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with mRNA vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using LC-MS/MS. Antibody-dependent phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD increased in Medigen-vaccinated individuals after the third dose. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.

Knowledge, attitude, and practice toward herpes zoster (HZ) and HZ vaccination: Concept elicitation findings from a multi-country study in the Asia Pacific.

Herpes zoster (HZ) is a prevalent disease characterized by a painful rash. A multi­country study was conducted to elicit public and physician knowledge, attitude, and practice (KAP) toward HZ disease and vaccination for the assessment of local factors influencing HZ vaccine perceptions in four Asian-Pacific countries/territories One-to-one qualitative interviews were conducted in 2022, among the public (people aged ≥ 50 years, adults with parents aged ≥ 50 years, zoster vaccine live-vaccinated individuals aged ≥ 50 years in Republic of Korea, and HZ patients; n = 78) and physicians (general practitioners and specialists; n = 24). Themes surrounding KAP toward HZ and HZ vaccination were summarized using a thematic analysis. A substantial knowledge gap related to HZ was observed among the public, including its causes, long-term impacts, and the at-risk population. There was a low perceived risk of HZ and low general awareness of HZ vaccine availability, although country/territory-specific differences existed. Fear of HZ-associated pain contributed toward vaccination intent among HZ patients and adults with parents aged ≥ 50 years. HZ-naïve adults who were encouraged to receive the vaccine by others were not motivated to do so due to optimism bias. Physicians were perceived to be a reliable source of information. However, physicians did not always proactively discuss HZ vaccination due to time constraints and a perceived need to prioritize other vaccinations including influenza and pneumococcal vaccines. Initiatives are needed to improve public awareness of HZ and its complications, in terms of overall impact on individuals and society, and highlight the important role of physicians in recommending vaccination.

Inhaled anesthesia associated with reduced mortality in patients with stage III breast cancer: A population-based study.

BACKGROUND: Patients diagnosed with stage III breast cancer often undergo surgery, radiation therapy, and chemotherapy as part of their treatment. The choice of anesthesia technique during surgery has been a subject of interest due to its potential association with immune changes and prognosis. In this study, we aimed to compare the mortality rates between stage III breast cancer patients undergoing surgery with propofol-based intravenous general anesthesia and those receiving inhaled anesthetics. METHODS: Using data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry, we identified a cohort of 10,896 stage III breast cancer patients. Among them, 1,506 received propofol-based intravenous anesthetic maintenance, while 9,390 received inhaled anesthetic maintenance. To ensure comparability between the two groups, we performed propensity-score matching. RESULTS: Our findings revealed a significantly lower mortality rate in patients who received inhaled anesthetics compared to those who received propofol-based intravenous anesthesia. Sensitivity analysis further confirmed the robustness of our results. CONCLUSIONS: This study suggests that inhaled anesthesia technique is associated with a lower mortality rate in clinical stage III breast cancer. Further research is needed to validate and expand upon these results.

Cordyceps sinensis accelerates stem cell recruitment to human skeletal muscle after exercise.

Cordyceps sinensis is a parasitic fungus known to induce immune responses. The impact of Cordyceps supplementation on stem cell homing and expansion to human skeletal muscle after exercise remains unexplored. In this study, we examined how pre-exercise Cordyceps supplementation influences cell infiltration, CD34+ cell recruitment, and Pax7+ cell expansion in human skeletal muscle after high-intensity interval exercise (HIIE) on a cycloergometer. A randomized, double-blind, placebo-controlled crossover study was conducted with 14 young adults (age: 24 ± 0.8 years). A placebo (1 g cornstarch) and Cordyceps (1 g Cordyceps sinensis) were administered before exercise (at 120% maximal aerobic power). Multiple biopsies were taken from the vastus lateralis for muscle tissue analysis before and after HIIE. This exercise regimen doubled the VEGF mRNA in the muscle at 3 h post-exercise (P = 0.006). A significant necrotic cell infiltration (+284%, P = 0.05) was observed 3 h after HIIE and resolved within 24 h. This response was substantially attenuated by Cordyceps supplementation. Moreover, we observed increases in CD34+ cells at 24 h post-exercise, notably accelerated by Cordyceps supplementation to 3 h (+51%, P = 0.002). This earlier response contributed to a four-fold expansion in Pax7+ cell count, as demonstrated by immunofluorescence double staining (CD34+/Pax7+) (P = 0.01). In conclusion, our results provide the first human evidence demonstrating the accelerated resolution of exercise-induced muscle damage by Cordyceps supplementation. This effect is associated with earlier stem cell recruitment into the damaged sites for muscle regeneration.

Baseline Blood Levels of Mucin-1 Are Associated with Crucial On-Treatment Adverse Outcomes in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Pirfenidone.

Mucin-1 is a multi-functional glycoprotein expressed by type II alveolocytes and may be detectable in the circulation following pulmonary fibrosis. The prognostic utility of baseline pre-treatment blood levels of mucin-1 in patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotics has not yet been fully established. We retrospectively studied a cohort of patients (from two hospitals) with IPF who were receiving pirfenidone for >12 weeks. Baseline blood mucin-1 levels were measured via sandwich enzyme-linked immunosorbent assays. We investigated the performance of mucin-1 levels in longitudinally predicting the risks of acute exacerbation of IPF (AE-IPF) and severe adverse outcomes (SAO), including lung transplantation and death. Seventy patients were included; 20 developed AE-IPF; and 31 had SAO during the follow-up period. Patients with baseline mucin-1 levels ≥2.5 ng/mL had enhanced risks of AE-IPF (adjusted hazard ratio [aHR], 14.07; 95% confidence interval [CI], 4.26-46.49) and SAO within 2 years (aHR, 7.87; 95% CI, 2.86-21.70) and anytime during the follow-up (aHR, 4.68; 95% CI, 2.11-10.39). The risks increased across subgroups with increasing mucin-1 levels. Patients in the "mucin-1 ≥ 2.5" group also exhibited an accelerated decline in DLCO. This study supports baseline blood mucin-1 levels as a biomarker for IPF that predicts adverse outcomes during pirfenidone treatment.

BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

BACKGROUND: Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. PATIENTS AND METHODS: We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. RESULTS: A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07) cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. CONCLUSIONS: Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

The Efficacy of Lactobacillus delbrueckii ssp. bulgaricus Supplementation in Managing Body Weight and Blood Lipids of People with Overweight: A Randomized Pilot Trial.

This study aimed to evaluate the efficacy of Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) in improving body weight, obesity-related outcomes, and lipid profiles of overweight people. Thirty-six overweight participants were randomly assigned to either a probiotic or a placebo group. A placebo powder or L. bulgaricus powder (containing 1 × 108 colony-forming unit (CFU) of the probiotic) was administered daily for 12 weeks. Body composition was determined, and blood tests were performed before and after the intervention. L. bulgaricus supplementation under the present condition did not affect the body weight, fat percentage, or body mass index (BMI) of the participants, while it resulted in a notable decrease in blood triglyceride (TG) levels, which corresponded to a lowering of the TG proportion in the composition of large VLDL (L-XXL sized fractions) and HDL (M and L fractions) in the probiotic-treated group. These results suggest that L. bulgaricus supplementation under the current conditions may not be helpful for losing weight, but it has the potential to decrease blood TG levels by modulating TG accumulation in or transport by VLDL/HDL in obese patients. L. bulgaricus supplements may have health-promoting properties in preventing TG-related diseases in overweight people.

Ethical challenges in the treatment of psychotic pregnancy denial.

Background: There is a paucity of literature regarding ethical strategies for treating pregnant people with psychosis. While not uncommon, psychotic pregnancy denial is a psychotic illness in which patients have the delusion that they are not pregnant. The authors provide a literature review regarding psychotic pregnancy denial, present an unpublished case and its questions and dilemmas, and offer recommendations for resolving the ethical challenges these cases raise. Case: A 26-year-old, single, unemployed woman of no fixed residence was admitted for suicidal ideation. She had a history of psychosis, had multiple ER visits and at least one previous hospitalization, had minimal contact with psychiatric outpatient clinics, and had been poorly compliant with treatment recommendations. She was discovered to be about 31 weeks pregnant in the emergency room. Ultrasound exams revealed no fetal anomalies. This was the patient's second pregnancy; her previous pregnancy resulted in an abortion. Her sole psychotic symptom was the delusional belief that she was not pregnant. On the rare occasions when the patient acknowledged being pregnant, she requested termination of pregnancy. Despite intensive pharmacological treatment of her psychosis, the patient continued believing that she was not pregnant and repeatedly said she would not participate in the labor and delivery process. She disagreed with the induction of labor or a cesarean section if needed. The patient developed gestational hypertension, an obstetric indication for delivery. Induction of labor was offered to avoid potentially disastrous outcomes for the pregnant woman and the fetus. Conclusion: Psychotic pregnancy denial is potentially life-threatening. Delivery of the fetus requires carefully weighing risks and benefits and thoroughly considering the ethical framework. Teaching points: Treatment of birthing people with psychotic denial of pregnancy is complex; it requires special clinical and ethical skills to determine the patient's level of decision-making impairment and to find a middle ground between the pregnant person's right to autonomy and the physicians' beneficence-based duties. Using a well-coordinated, interdisciplinary approach and a solid ethical framework, the decision to deliver the fetus while engaging the pregnant person, to the extent possible, in the decision-making process is essential.

A phase 3 randomized trial of the safety and immunogenicity of 20-valent pneumococcal conjugate vaccine in adults ≥ 60 years of age in Japan, South Korea, and Taiwan.

BACKGROUND: Pneumococcal infections are associated with high disease burden in older individuals in Japan, South Korea, and Taiwan. The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend protection beyond earlier pneumococcal vaccines. METHODS: This phase 3 randomized, double-blind study investigated the safety and immunogenicity of PCV20 in participants ≥ 60 years of age from Japan, South Korea, and Taiwan. Participants were randomized to receive PCV20 or 13-valent pneumococcal conjugate vaccine (PCV13). One month after vaccination, PCV20 recipients received a saline injection and PCV13 recipients received 23-valent polysaccharide vaccine (PPSV23). Primary immunogenicity objectives were to demonstrate noninferiority of PCV20 to PCV13 (13 matched serotypes) or PPSV23 (7 additional serotypes) for serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) 1 month after vaccination with PCV20, PCV13, or PPSV23. Noninferiority for each serotype was declared if the lower bound of the 2-sided 95% CI for OPA geometric mean ratio (GMR) was > 0.5. Safety endpoints included local reactions, systemic events, adverse events (AEs), and serious AEs. RESULTS: Overall, 1421‬ participants were vaccinated (median age [range]: 65 [60-85] years). PCV20 was noninferior to PCV13 for all 13 matched serotypes and to PPSV23 for 6 of 7 additional serotypes. Although statistical noninferiority was missed for serotype 8 (lower bound of the 2-sided 95% CI for OPA GMR = 0.5, thus not meeting the statistical noninferiority criterion of > 0.5), secondary immunogenicity endpoints for serotype 8 were supportive of a robust immune response. The incidence of AEs and the frequency and severity of local reactions and systemic events were generally similar after PCV20 and PCV13. No safety concerns were identified. CONCLUSION: PCV20 generated robust immune responses to all vaccine serotypes in older adults in Japan, South Korea, and Taiwan. The safety and tolerability profile was similar to PCV13. PCV20 is expected to help protect against all 20 vaccine serotypes. NCT04875533.