Objective: To identify factors associated with the absence of cervical spine instability in patients with rheumatoid arthritis (RA). Methods: Cervical spine instability was defined as the presence of at least one of the following: atlantoaxial subluxation, vertical subluxation of the axis, or subaxial subluxation. In 2001–2002, 634 enrolled outpatients with “classical” or “definite” RA underwent a radiographic cervical spine checkup. In 2012–2013, 233 (36.8%) prospectively underwent routine clinical follow-ups with a >10-year radiographic evaluation. The prevalence and independent predictive factors for no instability were analyzed by multivariable logistic regression. Next, 85 of 292 outpatients (29.1%) without baseline cervical spine instability completed consecutive >5-year and >10-year radiographic examinations. The incidence and predictors for no new development of instability were assessed similarly. Results: Among 233 patients, those without cervical spine instability decreased from 114 (48.9%) to 47 (20.2%) during >10 years. Steinbrocker peripheral joint destruction stages I–II (odds ratio [OR], 3.797; p=0.001), no corticosteroid administration (OR, 2.700; p=0.007), and no previous joint surgery (OR, 2.480; p=0.020) were predictors for no instability. Then, 33 of 85 (38.8%) consecutively followed patients without baseline cervical spine lesions did not develop instability throughout. Steinbrocker stages I–II (OR, 5.355; p=0.005) and no corticosteroid therapy (OR, 3.868; p=0.010) were predictors for no new onset of instability. C-reactive protein (CRP) level≤1.0 mg/dL was marginal in both models (n=233 [OR, 2.013; p=0.057], n=85 [OR, 2.453; p=0.075]). Conclusion Steinbrocker stages I–II, no corticosteroids, no previous joint surgery, and possibly CRP ≤1.0 mg/dL are factors associated with >10-year absence of cervical spine instability in RA.

Objective: To identify factors associated with the absence of cervical spine instability in patients with rheumatoid arthritis (RA). Methods: Cervical spine instability was defined as the presence of at least one of the following: atlantoaxial subluxation, vertical subluxation of the axis, or subaxial subluxation. In 2001–2002, 634 enrolled outpatients with “classical” or “definite” RA underwent a radiographic cervical spine checkup. In 2012–2013, 233 (36.8%) prospectively underwent routine clinical follow-ups with a >10-year radiographic evaluation. The prevalence and independent predictive factors for no instability were analyzed by multivariable logistic regression. Next, 85 of 292 outpatients (29.1%) without baseline cervical spine instability completed consecutive >5-year and >10-year radiographic examinations. The incidence and predictors for no new development of instability were assessed similarly. Results: Among 233 patients, those without cervical spine instability decreased from 114 (48.9%) to 47 (20.2%) during >10 years. Steinbrocker peripheral joint destruction stages I–II (odds ratio [OR], 3.797; p=0.001), no corticosteroid administration (OR, 2.700; p=0.007), and no previous joint surgery (OR, 2.480; p=0.020) were predictors for no instability. Then, 33 of 85 (38.8%) consecutively followed patients without baseline cervical spine lesions did not develop instability throughout. Steinbrocker stages I–II (OR, 5.355; p=0.005) and no corticosteroid therapy (OR, 3.868; p=0.010) were predictors for no new onset of instability. C-reactive protein (CRP) level≤1.0 mg/dL was marginal in both models (n=233 [OR, 2.013; p=0.057], n=85 [OR, 2.453; p=0.075]). Conclusion Steinbrocker stages I–II, no corticosteroids, no previous joint surgery, and possibly CRP ≤1.0 mg/dL are factors associated with >10-year absence of cervical spine instability in RA.

Objective: To identify factors associated with the absence of cervical spine instability in patients with rheumatoid arthritis (RA). Methods: Cervical spine instability was defined as the presence of at least one of the following: atlantoaxial subluxation, vertical subluxation of the axis, or subaxial subluxation. In 2001–2002, 634 enrolled outpatients with “classical” or “definite” RA underwent a radiographic cervical spine checkup. In 2012–2013, 233 (36.8%) prospectively underwent routine clinical follow-ups with a >10-year radiographic evaluation. The prevalence and independent predictive factors for no instability were analyzed by multivariable logistic regression. Next, 85 of 292 outpatients (29.1%) without baseline cervical spine instability completed consecutive >5-year and >10-year radiographic examinations. The incidence and predictors for no new development of instability were assessed similarly. Results: Among 233 patients, those without cervical spine instability decreased from 114 (48.9%) to 47 (20.2%) during >10 years. Steinbrocker peripheral joint destruction stages I–II (odds ratio [OR], 3.797; p=0.001), no corticosteroid administration (OR, 2.700; p=0.007), and no previous joint surgery (OR, 2.480; p=0.020) were predictors for no instability. Then, 33 of 85 (38.8%) consecutively followed patients without baseline cervical spine lesions did not develop instability throughout. Steinbrocker stages I–II (OR, 5.355; p=0.005) and no corticosteroid therapy (OR, 3.868; p=0.010) were predictors for no new onset of instability. C-reactive protein (CRP) level≤1.0 mg/dL was marginal in both models (n=233 [OR, 2.013; p=0.057], n=85 [OR, 2.453; p=0.075]). Conclusion Steinbrocker stages I–II, no corticosteroids, no previous joint surgery, and possibly CRP ≤1.0 mg/dL are factors associated with >10-year absence of cervical spine instability in RA.

Objective: To identify factors associated with the absence of cervical spine instability in patients with rheumatoid arthritis (RA). Methods: Cervical spine instability was defined as the presence of at least one of the following: atlantoaxial subluxation, vertical subluxation of the axis, or subaxial subluxation. In 2001–2002, 634 enrolled outpatients with “classical” or “definite” RA underwent a radiographic cervical spine checkup. In 2012–2013, 233 (36.8%) prospectively underwent routine clinical follow-ups with a >10-year radiographic evaluation. The prevalence and independent predictive factors for no instability were analyzed by multivariable logistic regression. Next, 85 of 292 outpatients (29.1%) without baseline cervical spine instability completed consecutive >5-year and >10-year radiographic examinations. The incidence and predictors for no new development of instability were assessed similarly. Results: Among 233 patients, those without cervical spine instability decreased from 114 (48.9%) to 47 (20.2%) during >10 years. Steinbrocker peripheral joint destruction stages I–II (odds ratio [OR], 3.797; p=0.001), no corticosteroid administration (OR, 2.700; p=0.007), and no previous joint surgery (OR, 2.480; p=0.020) were predictors for no instability. Then, 33 of 85 (38.8%) consecutively followed patients without baseline cervical spine lesions did not develop instability throughout. Steinbrocker stages I–II (OR, 5.355; p=0.005) and no corticosteroid therapy (OR, 3.868; p=0.010) were predictors for no new onset of instability. C-reactive protein (CRP) level≤1.0 mg/dL was marginal in both models (n=233 [OR, 2.013; p=0.057], n=85 [OR, 2.453; p=0.075]). Conclusion Steinbrocker stages I–II, no corticosteroids, no previous joint surgery, and possibly CRP ≤1.0 mg/dL are factors associated with >10-year absence of cervical spine instability in RA.

Objective: To identify factors associated with the absence of cervical spine instability in patients with rheumatoid arthritis (RA). Methods: Cervical spine instability was defined as the presence of at least one of the following: atlantoaxial subluxation, vertical subluxation of the axis, or subaxial subluxation. In 2001–2002, 634 enrolled outpatients with “classical” or “definite” RA underwent a radiographic cervical spine checkup. In 2012–2013, 233 (36.8%) prospectively underwent routine clinical follow-ups with a >10-year radiographic evaluation. The prevalence and independent predictive factors for no instability were analyzed by multivariable logistic regression. Next, 85 of 292 outpatients (29.1%) without baseline cervical spine instability completed consecutive >5-year and >10-year radiographic examinations. The incidence and predictors for no new development of instability were assessed similarly. Results: Among 233 patients, those without cervical spine instability decreased from 114 (48.9%) to 47 (20.2%) during >10 years. Steinbrocker peripheral joint destruction stages I–II (odds ratio [OR], 3.797; p=0.001), no corticosteroid administration (OR, 2.700; p=0.007), and no previous joint surgery (OR, 2.480; p=0.020) were predictors for no instability. Then, 33 of 85 (38.8%) consecutively followed patients without baseline cervical spine lesions did not develop instability throughout. Steinbrocker stages I–II (OR, 5.355; p=0.005) and no corticosteroid therapy (OR, 3.868; p=0.010) were predictors for no new onset of instability. C-reactive protein (CRP) level≤1.0 mg/dL was marginal in both models (n=233 [OR, 2.013; p=0.057], n=85 [OR, 2.453; p=0.075]). Conclusion Steinbrocker stages I–II, no corticosteroids, no previous joint surgery, and possibly CRP ≤1.0 mg/dL are factors associated with >10-year absence of cervical spine instability in RA.

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT).METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes.RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS.CONCLUSION: CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.
Antigens, CD274 ; Biopsy ; Carcinoma, Squamous Cell ; Disease-Free Survival ; Flow Cytometry ; Heavy Ion Radiotherapy ; Humans ; Radiotherapy ; Treatment Outcome ; Uterine Cervical Neoplasms

OBJECTIVE: Programmed cell death-ligand 1 (PD-L1) is expressed in tumor cells and has been shown to predict clinical outcomes of several types of malignancies. The aim of this study was to investigate the effects of carbon-ion (C-ion) beam irradiation on PD-L1 expression in human uterine cervical adeno/adenosquamous carcinoma (UCAA) cells and clinical samples and to identify the prognostic factors for outcomes after C-ion radiotherapy (CIRT). METHODS: The effects of C-ion irradiation on PD-L1 expression in human UCAA and cervical squamous cell carcinoma cells were examined by flow cytometry. We examined PD-L1 expression in UCAA biopsy specimens from 33 patients before CIRT started (pre-CIRT) and after 12 Gy (relative biological effectiveness [RBE]) irradiation (post-12Gy-C) in 4 fractions of CIRT to investigate the correlation between PD-L1 status and clinical outcomes. RESULTS: The PD-L1 expression was upregulated by C-ion beam in a dose-dependent manner in HeLa and SiHa cells through phosphorylated Chk1. The overall frequencies of pre-CIRT and post-12Gy-C PD-L1 positivity were 45% (15/33) and 67% (22/33), respectively. The post-12Gy-C PD-L1 expression was significantly elevated compared to the pre-CIRT PD-L1 expression. There was no significant relationship between the pre-CIRT PD-L1 status and clinical outcomes, such as local control (LC), progression-free survival (PFS), and overall survival (OS). However, the post-12Gy-C PD-L1 expression had better correlation with PFS, but not with LC and OS. CONCLUSION CIRT can induce PD-L1 expression in UCAA and we propose that PD-L1 expression after starting CIRT may become as a predictive prognostic marker in CIRT for UCAA.