Poor prognostic factors for relapse of interstitial lung disease in microscopic polyangiitis: the Japanese multicentre REVEAL cohort study.

This study investigated poor prognostic factors for the relapse of interstitial lung disease (ILD) in patients with microscopic polyangiitis (MPA) after remission induction therapy. We enrolled patients diagnosed with MPA complicated by ILD according to the Chapel Hill Consensus definition from 2001 to 2023 in multiple institutions in the REVEAL cohort. All patients who were treated with immunosuppressive therapy were followed up, and those who relapsed with ILD were extracted in this study. We explored the risk factors for predicting ILD relapse in patients with MPA-ILD by comparing the demographic, clinical, laboratory, and radiological findings and treatments between the relapsed and non-relapsed groups on admission. Of 243 patients with MPA, 134 (55.1%) with MPA-ILD were enrolled. Among them, 28 (20.9%) relapsed during a mean follow-up of 4.2 years. The initial serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) levels and the prevalence of usual interstitial pneumonia (UIP) pattern were significantly higher in the relapsed group. The biomarkers were also risk factors for relapse in multivariate Cox regression analysis. The best cut-off values of KL-6, SP-D for predicting ILD relapse were 430 U/mL and 89.5 ng/mL, respectively. We created prediction models based on the best cut-off values for KL-6, SP-D, and the presence of the UIP pattern (KSU model). The 10-year relapse rate was significantly different among patients with MPA-ILD stratified by the number of risk factors based on the KSU model. A higher relapse rate was associated with higher all-cause mortality. The initial serum high KL-6 and SP-D levels and the prevalence of the UIP pattern were associated with ILD relapse in patients with MPA-ILD. Our multicentre cohort study indicated that the KSU model, which consists of KL-6 ≥ 430 U/mL, SP-D ≥ 89.5 ng/mL, and the presence of the UIP pattern, is a useful predictor of ILD relapse in patients with MPA after immunosuppressive therapy.

Matsuda S ，Kotani T ，Okazaki A ，Nishioka D ，Masuda Y ，Shiomi M ，Watanabe R ，Taniguchi T ，Manabe A ，Kadoba K ，Yoshida T ，Hiwa R ，Yamamoto W ，Hashimoto M ，Takeuchi T ... -  《-》

[Diagnostic significance of serum chemokine CXCL-10 and Krebs von den lungen-6 level in patients with rheumatoid arthritis associated interstitial lung disease].

Yan R ，Ke D ，Zhang Y ，Li L ，Su H ，Chen W ，Sun M ，Liu X ，Luo L ... -  《-》

Clinical features, radiological findings and prognosis of microscopic polyangiitis with interstitial lung disease: a retrospective matched control study.

The association between interstitial lung disease (ILD) and microscopic polyangiitis (MPA) has received increasing attention in recent years. However, there are still no studies comparing clinical characteristics and prognoses between MPA-ILD patients and patients with ANCA-negative ILDs. Therefore, the purpose of this study was to analyse a group of patients presenting MPA-ILD matched with patients exhibiting ANCA-negative ILDs to identify differences in their clinical characteristics and survival. This study retrospectively reviewed the data of 60 patients with MPA-ILD and 60 patients with ANCA-negative ILDs who were matched for age, sex, and patterns on chest high-resolution CT (HRCT) images. The baseline clinical information, laboratory parameters and chest CT data were collected and analysed at each patient's initial diagnosis. Sixty of the 682 (8.8%) ILD patients were diagnosed with MPA-ILD. MPA-ILD patients tended to be older and have higher CRP and ESR levels. ILD antedated MPA in 61.7% (37/60) of the patients, and MPA occurred on average (45.1 ± 33.4) months after the ILD diagnosis. Compared with matched ANCA-negative ILD patients, MPA-ILD patients had higher CRP and serum creatinine levels and lower haemoglobin levels. UIP (63.3%) was the most common chest HRCT pattern, and the proportion of patients with oddly shaped cysts (P = 0.04) was significantly greater in the MPA-ILD group than in the matched ANCA-negative ILD group. The number of MPA-ILD patients was significantly shorter than that of ANCA-negative ILD patients (P = 0.005). Survival analysis revealed that acute exacerbation (AE) of ILD (HR 2.40, 95% CI 1.03-5.59, P = 0.043) and diffuse alveolar haemorrhage (HR 3.42, 95% CI 1.09-10.73, P = 0.036) were independently associated with shorter survival and that receiving glucocorticoids combined with immunosuppressants (HR 0.11, 95% CI 0.03-0.37, P < 0.001) was independently associated with prolonged survival in MPA-ILD patients. The proportion of MPA-ILD patients with total ILD is not low, and ANCA testing of ILD patients is necessary. Oddly shaped cysts with a UIP pattern may be a characteristic chest imaging manifestation of MPA-ILD. The prognosis of MPA-ILD is poor, especially for patients who are older, have DAH, and have experienced AEs.

Song Q ，Liu Y ，Wu T ，Zhang Y ，Yan Y ，Xiao S ... -  《BMC Pulmonary Medicine》

Evaluating the diagnostic and prognostic utility of serial KL-6 measurements in connective tissue disease patients at risk for interstitial lung disease: correlations with pulmonary function tests and high-resolution computed tomography.

Interstitial lung diseases associated with connective tissue diseases (CTD-ILD) necessitate reliable biomarkers for effective management. This study assesses the utility of serial Krebs von den Lungen-6 (KL-6) measurements in predicting disease activity and progression in CTD-ILD patients. In a prospective cohort study at a tertiary care center, 50 patients with CTD at risk of or diagnosed with ILD were enrolled. KL-6 levels and pulmonary function tests (PFTs) were measured at baseline, 6, and 12 months, alongside high-resolution computed tomography (HRCT). Initial KL-6 levels were inversely correlated with PFTs, with mean values starting at 504.96 U/mL (SD ± 508.46), escalating to 739.42 U/mL (SD ± 612.75) at 6 months, and peaking at 1150.27 U/mL (SD ± 1106.70) by 12 months, reflecting disease progression. Higher KL-6 levels were consistently linked with declines in Forced Vital Capacity (FVC) (p = 0.019) and Diffusing Capacity for Carbon Monoxide (DLCO) (p < 0.001). Radiologically, increased KL-6 correlated with subpleural thickening (p = 0.003), septal thickening (p = 0.036), ground-glass opacities (p = 0.018), and other signs of advanced ILD. Sensitivity and specificity of KL-6 for detecting ILD were 86.7% and 71.4%, respectively, at a ≥ 400 U/mL threshold, improving at higher thresholds. Over the study period, patients with elevated KL-6 levels demonstrated more pronounced radiological and functional deterioration. Serial KL-6 measurements effectively reflect disease activity and progression in CTD-ILD, with strong correlations to functional and radiological outcomes. These findings support the use of KL-6 as a valuable biomarker in the routine clinical management of these complex disorders. Our study demonstrates the significant predictive value of KL-6 for both the diagnosis and monitoring of CTD-ILD, suggesting its integration into clinical practice can enhance patient care and treatment strategies.

Álvarez Troncoso J ，Porto Fuentes Ó ，Fernández Velilla M ，Gómez Carrera L ，Soto Abánades C ，Martínez Robles E ，Sorriguieta Torre R ，Ríos Blanco JJ ... -  《BMC Pulmonary Medicine》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》