Longitudinal antibody dynamics after COVID-19 vaccine boosters based on prior infection status and booster doses.

Global concern over COVID-19 vaccine distribution disparities highlights the need for strategic booster shots. We explored longitudinal antibody responses post-booster during the Omicron wave in a Japanese cohort, emphasizing prior infection and booster doses. This prospective cohort study included 1763 participants aged 18 years and older with at least three vaccine doses (7376 datapoints). Antibody levels were measured every 2 months. We modeled temporal declines in antibody levels after COVID-19 vaccine boosters according to prior infection status and booster doses using a Bayesian linear mixed-effects interval-censored model, considering age, sex, underlying conditions, and lifestyle. Prior infection enhanced post-booster immunity (posterior median 0.346, 95% credible interval [CrI] 0.335-0.355), maintaining antibody levels (posterior median 0.021; 95% CrI 0.019-0.023) over 1 year, in contrast to uninfected individuals whose levels had waned by 8 months post-vaccination. Each additional booster was correlated with higher baseline antibody levels and slower declines, comparing after the third dose. Female sex, older age, immunosuppressive status, and smoking history were associated with lower baseline post-vaccination antibodies, but not associated with decline rates except for older age in the main model. Prior infection status and tailored, efficient, personalized booster strategies are crucial, considering sex, age, health conditions, and lifestyle.

Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study.

This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD.

Significance of Continuous Low-Dose Lenvatinib for the Treating of the Patients with Unresectable Thyroid Carcinoma.

The tyrosine kinase inhibitor lenvatinib has been confirmed as an effective treatment option for patients with unresectable thyroid carcinoma. We conducted a retrospective analysis of the significance of the effect of continued lenvatinib treatment for the longest duration possible at a reasonable daily dose and with a minimum discontinuation period in 42 patients with unresectable thyroid carcinoma treated with lenvatinib between 2015 and 2020. A Cox proportional hazard model-based analysis revealed that the overall survival of the patients treated with a <8 mg/day mean dose of lenvatinib was significantly better than that of the patients treated with 8-24 mg/day (hazard ratio [HR] 0.38 for 1.14-4.54 mg/day, and HR 0.01 for 4.56-7.97 mg/day) adjusted for various factors (e.g., sex, age, drug interruption period). The cumulative dose of lenvatinib administered tended to be higher in the patients treated with low doses (< 8 mg/day) than in the patients treated with relatively high doses (8-24 mg/day). Considering its adverse events, the continuation of lenvatinib treatment with an adequate daily dose and drug interruption may help prolong the survival of patients with unresectable thyroid carcinoma.

Complementary and Alternative Medicine Use, Cancer Screening, and Medical Checkups in Japan from 2001 to 2013: A Repeated Cross-Sectional Study.

Introduction: The association between complementary and alternative medicine (CAM) use and other health-related behaviors is an important issue. A previous study reported that complementary medicine use is related to greater use of cancer screening, whereas alternative medicine use is related to lower use of cancer screening. Given the sparse evidence from Japan, we aimed to examine the association of CAM use with cancer screening and medical checkups. We used a repeated cross-sectional survey of a nationally representative sample of Japanese people and conducted age-period-cohort analysis. Methods: The study population was 68,217 of 83,827 individuals observed from 2001 to 2013 who received cancer screening. CAM users were defined as individuals who received acupuncture, moxibustion, anma/massage/shiatsu, or judo therapy for their most worrisome symptom. The outcomes of interest were receiving stomach, lung, colorectal, uterine, and breast cancer screenings and medical checkups. Using crossclassified multilevel logistic regression models, we estimated odds ratios (ORs) and 95% credible intervals (CIs) for cancer screening and medical checkups. Results: For CAM users of complementary medicine, the adjusted ORs for stomach, lung, and colorectal cancer screening were 1.40 (95% CI: 1.35-1.44), 1.37 (95% CI: 1.34-1.40), and 1.52 (95% CI: 1.49-1.54), respectively. We found similar results for uterine and breast cancer screening, and medical checkups. Conclusions: Irrespective of whether they use CAM, CAM users in Japan tend to receive a variety of cancer screenings and medical checkups.

EGFR Mutation is a Prognostic Factor in Lung Cancer Patients with Pleural Dissemination Detected During or After Surgery.

BACKGROUND: Primary lung tumors are sometimes resected when either pleural dissemination (PD) or malignant pleural effusion (MPE) exists. This study clarified the prognostic factors for non-small cell lung cancer (NSCLC) with either PD and MPE, or both, detected during or after surgery. PATIENTS AND METHODS: We examined patients with NSCLC from a multicenter database who had either PD, MPE, or both, detected during or after surgery between 2005 and 2015. Hazard ratios and 95% confidence intervals were estimated using the Cox proportional hazards model adjusted for potential confounding factors. RESULTS: Among 9463 registered patients, PD, MPE, or both, were found in 114 patients with NSCLC during or after surgery. Primary tumor resection and exploratory thoracotomy were performed in 65 and 49 patients, respectively. In univariate analysis, adenocarcinoma, clinically undetected lymph node metastasis (c-N0 or unknown), EGFR mutation, and combination of chemotherapy or tyrosine kinase inhibitors after surgery were better prognostic factors for overall survival (OS), whereas in the multivariate analysis, adenocarcinoma, clinically undetected lymph node metastasis, and EGFR mutation were favorable independent prognostic factors in OS. Additionally, limited to patients with EGFR mutation, patients with primary lung tumor resection showed a significantly better 5-year OS than those with exploratory thoracotomy (86.4 vs. 44.8%; p < 0.001). CONCLUSION: Our findings show that surgical resection of primary tumors could improve the prognosis of patients with PD, MPE, or both, detected during or after surgery when the tumors harbor an EGFR mutation.

Outcomes of solitary postoperative recurrence of esophageal squamous cell carcinoma diagnosed with FDG-PET/CT and treated with definitive radiation therapy.

BACKGROUND: Surgical resection of esophageal cancer is frequently performed to achieve a complete cure. However, the postoperative recurrence rate is 36.8-42.5%, leading to poor prognosis. Radiation therapy has been used to treat recurrences; solitary recurrence has been proposed as a prognostic factor for radiation therapy, though its significance is unclear. 18F-fluorodeoxyglucose positron emission tomography is a highly accurate diagnostic modality for esophageal cancer. This retrospective study aimed to analyze the outcomes of solitary postoperative recurrences of esophageal squamous cell carcinoma diagnosed with 18F-fluorodeoxyglucose positron emission tomography and treated with definitive radiation therapy. METHODS: We examined 27 patients who underwent definitive radiation therapy for single or multiple postoperative recurrences of esophageal squamous cell carcinoma between May 2015 and April 2021. 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed within 3 months before the commencement of radiation therapy. Kaplan-Meier, univariate, and multivariate analyses were performed to examine the overall survival and identify potential prognostic factors. RESULTS: The 1-, 2-, and 3-year overall survival rates were 85.2%, 62.6%, and 47.3%, respectively, and solitary recurrence was the only significant factor associated with overall survival (P = 0.003). The 1-, 2-, and 3-year overall survival rates in patients with solitary recurrence were 91.7%, 80.2%, and 80.2%, respectively, and in patients with multiple recurrences they were 80.0%, 50.3%, and 25.1%, respectively. Multivariate analysis also showed solitary recurrence as a significant factor for overall survival. CONCLUSIONS: When diagnosed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography, solitary recurrence appears to have a more favorable prognosis than multiple recurrences.

Frailty and all-cause and cause-specific mortality in Japan.

BACKGROUND: In aging societies, there is an increasing focus on the concept of frailty. However, there is no consistent means to assess this concept. We assessed frailty using the Kihon Checklist (KCL), which is widely used in Japan, and examined the association between frailty and all-cause and cause-specific mortality in Japan, the most aged society in the world. METHODS: This was a retrospective cohort study, and we analyzed 43,312 participants aged ≥ 65 years who were enrolled in basic health checkups in Okayama City, Japan. We defined the frailty status of the participants using the KCL. To assess the association of frailty status with all-cause and cause-specific mortality, we used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs), adjusting for individual potential confounders. Mean follow-up time was 9.3 years. RESULTS: The fully adjusted HR for all-cause mortality was 1.34 (95% confidence interval [CI]: 1.27-1.41) for the prefrail group and 2.22 (95% CI: 2.11-2.33) for the frail group. A similar pattern was observed for cardiovascular disease, respiratory disease, and cancer mortality. Younger people (65-74 years) and women tended to have higher effect estimates than older people (≥ 75 years) and men. CONCLUSION: Prefrailty and frailty can increase the risk of both all-cause and cause-specific mortality. Our study suggests that to support frail patients, it could be effective to focus on the prevention and management of cardiovascular and respiratory disease, and that the KCL may be useful as a method of screening for frailty.

Breastfeeding at 6 months of age had a positive impact on overweight and obesity in Japanese adolescents at 15 years of age.

AIM: A number of studies have indicated the potential benefits that breastfeeding has on reducing childhood obesity, but few studies have evaluated the effect on adolescent obesity. We examined the association between breastfeeding and overweight or obesity at 15 years of age using data from a large nationwide longitudinal study launched by the Japanese Government in 2001. METHODS: We analysed data for 26 164 participants with known infant feeding practices at 6 months of age, namely the duration of breastfeeding or formula feeding. Overweight or obesity at 15 years of age were calculated based on the subject's self-reported height and weight. Multinomial logistic regression analysis adjusted the data for child factors, namely sex, siblings, birth weight and physical activity clubs and the maternal factors of age, educational attainment and smoking status. RESULTS: Formula feeding was associated with an increased risk of overweight or obesity at 15 years of age. The adjusted odds ratios (95% confidence intervals) were 0.99 (0.89-1.09) for partial breastfeeding and 1.23 (1.02-1.48) for formula feeding, when exclusive breastfeeding was the reference category. CONCLUSION: Breastfeeding during infancy had potential benefits for overweight or obesity among 15-year-old adolescents. Our results provide further evidence of the importance of breastfeeding.

A Simple and Descriptive Assessment of Morphology Based on the Horizontal Plane of the Pediatric Head and Creation of a Normative Database in Japanese Children 6 Years Old and under: Horizontal Vector Analysis.

We herein introduce horizontal vector analysis, a simple method for assessing cranial morphology based on measurement of the head's horizontal plane, and use this method to establish normal cranial morphology in Japanese children Computed tomography scans taken in 2010-2019 in healthy Japanese children aged ≤ 6 years. The two measurement planes were parallel to the orbitomeatal plane: namely, a plane passing through the dorsum sellae (DS) and the plane superior to that with the maximal area (Max plane). A protractor was used to circumferentially measure the lengths from the central point to the outer surface of the skull. A total of 487 images were extracted. The distances between the DS and Max planes were consistently almost 30 mm for each age group, so we fixed the Max plane as the plane 30 mm superior to the DS plane. Finally, we established datasets of normal values for each age group and sex. Using these norms, perioperative evaluation of various cranial deformities could be performed more easily and circumstantially.

The validity of atypical psychosis diagnostic criteria to detect anti-NMDA receptor encephalitis with psychiatric symptoms.

Anti-NMDAR encephalitis has a psychotic presentation that is difficult to distinguish from primary psychosis. An atypical psychosis that is similar to schizophrenia, mood disorder, and epilepsy is unique, and the original diagnostic criteria exist only in Japan. The clinical symptoms and courses of anti-NMDAR encephalitis and atypical psychosis are very similar. We investigated whether the diagnostic criteria of atypical psychosis are useful to increase the detection rate of anti-NMDAR encephalitis with psychiatric symptoms. The presence of anti-NR1/NR2B IgG antibodies in the cerebrospinal fluid of 218 newly admitted inpatients initially diagnosed with schizophrenia (n = 151), mood disorder (n = 47), or epilepsy with psychiatric symptoms (n = 20) was assessed by cell-based assay. Of 218 patients, 123 (36.3 years ± SD 17.2, 69.9 % females) fulfilled the diagnostic criteria of category B for atypical psychosis. All 12 patients (9.8 %, 12/123) with anti-NR1/NR2B IgG antibodies fulfilled category B of atypical psychosis statistically better than the patients without anti-NR1/NR2B IgG antibodies (P = 0.0009). Of the 12 patients with anti-NMDAR antibodies, two did not fulfill either criteria of catatonia (DSM-5) or Graus' diagnostic criteria of anti-NMDAR encephalitis during the time course, and 11 patients showed good prognosis with early immunotherapies. In ROC analysis, abnormal electroencephalogram findings showed the highest sensitivity (0.833) for detection of anti-NR1/NR2B IgG antibodies, and 31.3 % of patients with category B atypical psychosis and abnormal electroencephalogram findings had anti-NMDAR antibodies. Lumbar puncture and detection of anti-NMDAR antibodies should be considered for patients who fulfill atypical psychosis diagnosis criteria with an abnormal electroencephalogram.

Candidemia in patients with head and neck cancer: mortality and a novel risk factor.

PURPOSE: Candidemia is a bloodstream infection (BSI) by Candida spp. and is associated with high mortality. However, there have been few reports about BSI in head and neck cancer (HNC). We aimed to evaluate the impact of candidemia in patients with HNC and compared it with bacteremia. STUDY DESIGN: A multicenter retrospective study. METHODS: We retrospectively analyzed 83 BSI episodes in HNC (2011 to 2020) and divided them into the candidemia and bacteremia groups. We then compared the survival rate and risk factors for candidemia between the groups. RESULTS: The overall cumulative incidence (risk) of candidemia in BSI was 12 out of 83 episodes (14.5%). The 1-year mortality for the bacteremia and candidemia groups was 33.3% and 58.3%, respectively (log-rank p = 0.041). Broad-spectrum antibiotics (odds ratio [OR]: 29.5; 95% confidence interval [CI], 2.49-350), mucositis (OR 11.0; 95% CI, 1.52-80.1), and malignant wounds (OR 79.5; 95% CI 1.33-4737) were significant risk factors for candidemia in HNC. CONCLUSIONS: Candidemia causes high mortality in patients with HNC. To our knowledge, malignant wounds have not been previously reported as a risk factor for candidemia. For early diagnosis and treatment of candidemia, risk factors should be considered, and antifungal therapy started earlier.

Static posturographic balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing process.

BACKGROUND: Understanding how sensorineural hearing loss (SNHL) impacts postural balance in patients is important, as postural balance predicts the risk of falls. AIMS/OBJECTIVES: We aimed to clarify the relationship between characteristics in the configuration of audiograms and static postural balance as measured by posturography. MATERIALS AND METHODS: We evaluated 385 outpatients (mean [± standard deviation] age, 58.4 ± 18.4 years) with SNHL by audiometry and posturography. Data were analysed by multiple regression models with the outcome of postural sway area with eyes closed (PSA) and predictive variables of audiometric data, adjusted for sex, age and the presence of nystagmus. RESULTS: The increased hearing threshold in the better hearing ear was associated with poorer or higher PSA (beta coefficient [ß] = 0.39, 95% confidence interval [CI] = 0.03-0.75, per 10-dB increment). No difference in PSA was detected between patients with asymmetric or symmetric SNHL. None of the frequent diagnoses (presbyacusis, Meniere's disease, and idiopathic sudden SNHL) were associated with poorer PSA. Hearing thresholds at middle (ß = 0.39, 95%CI = 0.10-0.67) and high frequencies (ß = 0.31, 95%CI = 0.07-0.55) were associated with poorer PSA, whereas those at low frequencies was not. CONCLUSIONS AND SIGNIFICANCE: Postural balance in neurotologic patients may be associated with middle-high-frequency hearing levels during ageing.

Clinical moderators of response to nalmefene in a randomized-controlled trial for alcohol dependence: An exploratory analysis.

BACKGROUND: Nalmefene is the only medication marketed to reduce the consumption of alcohol in patients with alcohol dependence, but it remains unclear which patients could most benefit from it. This study aimed to identify clinical moderators that affect treatment response to nalmefene in patients with alcohol dependence. METHODS: In a multicenter, randomized, controlled, double-blind, phase 3 study of nalmefene on Japanese patients with alcohol dependence, the relationship between the reduction of heavy drinking days (HDD) and total alcohol consumption (TAC) at 12 and 24 weeks of treatment and baseline variables of the participants were analyzed in a linear regression and multiple adjusted analysis. RESULTS: Age < 65, no family history of problem drinking, age at onset of problem drinking ≥ 25, and not currently smoking were possible positive moderators. Nalmefene showed a significant HDD reduction in patients with age < 65 or no family history of problem drinking, and a significant TAC reduction in patients with age at onset of problem drinking ≥ 25 or who were not currently smoking. After multiple adjusted analyses, age < 65 (p = .028), no family history of problem drinking (p = .047), and age at onset of problem drinking ≥ 25 (p = .030) were statistically significant. Not currently smoking (p = .071) was marginally significant. In combination, these moderators indicated synergistic effects. CONCLUSIONS: Alcohol-dependent patients with favorable prognostic factors such as non-smoking status, no family history of problem drinking, and a late-onset of problem drinking selectively benefit from nalmefene. Further research is needed to validate these exploratory results.

Impairment of early neuronal maturation in anti-NMDA-receptor encephalitis.

RATIONALE: Adequate immunotherapies for anti-NMDAR encephalitis during pregnancy produce a relatively good clinical outcome for pregnant mothers and their infants, but there are no reports about the future growth of their babies. The damage of anti-NMDAR antibodies to early neuronal development is still unknown. OBJECTIVES: Serum or cerebrospinal fluid from one patient with anti-NMDAR encephalitis (the index patient) and one patient with schizophrenia (the control patient) was administered to primary cultures of dissociated rat cortical neurons, and dendritic outgrowth, centrosome elimination, and branching of dendrites were investigated. For rescue experiments, serum of the index patient was replaced with normal culture media after 3 days' administration of the index patient. RESULTS: Serum and cerebrospinal fluid of the index patient statistically significantly impaired dendritic outgrowth of cultured rat cortical primary neurons. Serum of the index patient also statistically significantly delayed centrosome elimination. Impaired dendritic outgrowth and delayed centrosome elimination were not perfectly rescued by changing to normal culture media. Serum of the index patient also statistically significantly reduced the branching of dendrites. CONCLUSIONS: This is the first demonstration of the damage by anti-NMDAR antibodies on early dendritic development in vitro. As a strategy to protect embryonic neurons, our findings may support the efficacy of early immunotherapy for anti-NMDAR encephalitis in pregnancy.

PD-L1 expression in tongue squamous cell carcinoma.

PURPOSE: Immune checkpoint proteins programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important therapeutic targets for head and neck cancer. This large-scale case study aimed to analyze tongue squamous cell carcinomas (SCCs) and evaluate the correlation between PD-L1 expression and clinical prognosis. So far, this study is the largest case study on PD-L1 expression in tongue SCCs. METHODS: This is a case-control study that analyzed 121 tongue SCCs. Paraffin-embedded sections and clinical data were obtained retrospectively and immunohistochemistry with PD-L1 was performed. RESULTS: 11.6% contained ≥ 50% of PD-L1-positive cells, 57.1% of these cases had a poor prognosis with nodal metastasis. Among cases of T1/2 primary lesions with nodal metastasis, cases of high PD-L1 expression had a significantly shorter disease-free survival than cases of no PD-L1 expression (p = 0.018). The hazard ratio for high PD-L1 expression was 3.21 (95 per cent CI, 1.26-8.72) compared with no PD-L1 expression after adjusting for other factors. CONCLUSIONS: These data indicate that PD-L1 upregulation in tongue SCCs is associated with a more advanced stage and shorter disease-free survival. PD-1/PD-L1 inhibitors might hence constitute potential adjuvant therapy for tongue SCCs with PD-L1 upregulation.

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis.

BACKGROUND: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. METHODS: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. RESULTS: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. CONCLUSIONS: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence.

MACC1 expression is an indicator of recurrence in early-stage glottic cancer.

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) has been reported to be an independent indicator of poor prognoses in some kinds of cancer due to disease metastasis or recurrence. We investigated the correlation between MACC1 expression and the prognosis of glottic cancer. METHODS: Paraffin-embedded, early-stage (I or II) glottic cancer specimens (n = 52) were immunohistochemically analyzed to explore MACC1 expression. The clinical records associated with each case were also examined. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method, and between-group RFS differences were assessed using the log-rank test. The multivariate analyses were evaluated using the Cox's proportional-hazard model. RESULTS: Patients were treated with only radiotherapy (RT) (n = 37, including 18 with T1 disease and 19 with T2 disease), or with chemoradiotherapy (CRT) (n = 15, including 1 with T1 disease and 14 with T2 disease). Eleven patients demonstrated local recurrence and two patients experienced cervical lymph node recurrence. Tumor specimens were MACC1-positive in 9 of the 13 (69.2%) patients with local or neck recurrence, and 7 of the 11 (63.6%) patients with local recurrence. The RFS rate of patients who were treated with only RT was significantly lower than that of patients who were treated with CRT (P = 0.0243). The RFS rate was significantly lower in cases with MACC1 expression than in those without MACC1 expression (P = 0.0003). Multivariate analysis revealed that MACC1 expression was an independent risk factor of local recurrence (P = 0.0016). CONCLUSION: MACC1 is an independent indicator of recurrence related to RFS in early-stage glottic cancer.

Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis.

BACKGROUND: IgG4 production is regulated by type 2 (IL-4 and IL-13) and regulatory (IL-10) cytokines involved in the pathophysiology of chronic rhinosinusitis (CRS). We sought to determine the pathophysiological characteristics of IgG4-positive cells in sinonasal tissues in CRS, especially eosinophilic CRS (ECRS). METHODS: IgG4-positive cells in uncinate tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. Associations between the number of IgG4-positive cells and clinicopathological factors were analyzed. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of IgG4-positive cells in tissue that can predict the post-operative course. RESULTS: IgG4 was mainly expressed in infiltrating plasma and plasmacytoid cells, and the number of IgG4-positive cells was significantly higher in NP, especially those from severe ECRS patients, than in UT. In CRS patients, the number of IgG4-positive cells significantly and positively correlated with blood and tissue eosinophilia, radiological severity, and serum level of total IgE. The number of infiltrating IgG4-positive cells was significantly higher in patients with a poor post-operative course (sustained sinus shadow 6 months after surgery) than in those with a good one. The number of IgG4-positive cells in NP could discriminate patients with a good or a poor post-operative course (area under the curve: 0.769). Also, 73.3% sensitivity and 82.5% specificity were achieved when the cut-off value was set at 17 cells/high-power field. CONCLUSIONS: Our results suggest that the local expression of IgG4 on cells may be used as a biomarker that reflects the pathophysiology of CRS, including the post-operative course.