Cumulative rib fracture risk after stereotactic body radiotherapy in patients with localized non-small cell lung cancer.

INTRODUCTION: Rib fracture is a known complication after stereotactic body radiotherapy (SBRT). Patient-related parameters are essential to provide patient-tailored risk estimation, however, their impact on rib fracture is less documented compared to dosimetric parameters. This study aimed to predict the risk of rib fractures in patients with localized non-small cell lung cancer (NSCLC) post-SBRT based on both patient-related and dosimetric parameters with death as a competing risk. MATERIALS AND METHODS: In total, 602 patients with localized NSCLC treated with SBRT between 2010-2020 at Odense University Hospital, Denmark were included. All patients received SBRT with 45-66 Gray (Gy)/3 fractions. Rib fractures were identified in CT-scans using a word embedding model. The cumulative incidence function was based on cause-specific Cox hazard models with variable selection based on cross-validation model likelihood performed using 50 bootstraps. RESULTS: In total, 19 % of patients experienced a rib fracture. The cumulative risk of rib fracture increased rapidly from 6-54 months post-SBRT. Female gender, bone density, near max dose to the rib, V30 and V40 to the rib, gross tumor volume, and mean lung dose were significantly associated with rib fracture risk in univariable analysis. The final multi-variable model consisted of V20 and V30 to the rib and mean lung dose. CONCLUSION: Female gender and low bone density in male patients are significant predictors of rib fracture risk. The final model predicting cumulative rib fracture risk of 19 % in patients with localized NSCLC treated with SBRT contained no patient-related parameters, suggesting that dosimetric parameters are the primary drivers.

Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis.

Introduction: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC. Methods: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-É£, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC. Results: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-É£, ZYM-IFN-É£, ZYM-TNF-α, ZYM-IL-1ß, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-É£, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity. Discussion: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.

Validity of Major Osteoporotic Fracture Diagnoses in the Danish National Patient Registry.

Objective: To evaluate the validity of diagnosis codes for Major Osteoporotic Fracture (MOF) in the Danish National Patient Registry (NPR) and secondly to evaluate whether the fracture was incident/acute using register-based definitions including date criteria and procedural codes. Methods: We identified a random sample of 2400 records with a diagnosis code for a MOF in the NPR with dates in the year of 2018. Diagnoses were coded with the 10th revision of the International Classification of Diseases (ICD-10). The sample included 2375 unique fracture patients from the Region of Southern Denmark. Medical records were retrieved for the study population and reviewed by an algorithmic search function and medical doctors to verify the MOF diagnoses. Register-based definitions of incident/acute MOF was evaluated in NPR data by applying date criteria and procedural codes. Results: The PPV for MOF diagnoses overall was 0.99 (95% CI: 0.98;0.99) and PPV=0.99 for the four individual fracture sites, respectively. Further, analyses of incident/acute fractures applying date criteria, procedural codes and using patients' first contact in the NPR resulted in PPV=0.88 (95% CI: 0.84;0.91) for hip fractures, PPV=0.78 (95% CI: 0.74;0.83) for humerus fractures, PPV=0.78 (95% CI: 0.73;0.83) for clinical vertebral fractures and PPV=0.87 (95% CI: 0.83;0.90) for wrist fractures. Conclusion: ICD-10 coded MOF diagnoses are valid in the NPR. Furthermore, a set of register-based criteria can be applied to qualify if the MOF fracture was incident/acute. Thus, the NPR is a valuable and reliable data source for epidemiological research on osteoporotic fractures.