Pneumocystis jirovecii pneumonia increases the 3-months mortality of anti-MDA5-antibody-positive dermatomyositis patients.
Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+DM) patients are associated with considerable mortality, and opportunistic infections including Pneumocystis jirovecii pneumonia (PJP)is the main cause. This study was to identify clinical characteristics, risk factors, and prognostic factors of PJP diagnosed by bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in anti-MDA5+ DM patients.
In this retrospective observational study, all patients admitted with suspected pneumonia were detected for mNGS in BALF. The demographics, comorbidities, laboratory parameters, and treatments of the patients were compared and analyzed in both groups to identify the potential risk factors for PJP and death via Logistic regression and Cox proportional hazards regression, respectively.
Overall, 92 patients were included in this study, 46(50.0%) were defined as PJP+ group, and the other 46 (50.0%) as PJP- group, and 31(67.4%) PJP occurred in the first 3 months. Increased neutrophil-lymphocyte ratio (NLR) and CRP were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all p<0.05). The three-months mortality rate was higher in the PJP+ group compared to PJP- group (43.5% vs 23.9%, p=0.047). Rapidly progressive interstitial lung disease (RPILD) was a main predictor of mortality in anti-MDA5+DM patients with PJP, whereas glucocorticoid use was a significant protective factor.
PJP has high prevalence and mortality in anti-MDA5+DM, while TMP/SMZ prophylaxis significantly reduces PJP risk. Mortality in PJP+ patients is primarily concentrated within the first 3 months, associated with RPILD. Early intervention with corticosteroids and prophylactic measures are crucial in reducing mortality.
Gao C
，Wei G
，Zhang C
，Wang C
，Li C
，Li R
，Su Z
，Zheng Z
... -
《Frontiers in Immunology》
The evaluation of type I interferon score in dermatomyositis, a systematic review and a meta-analysis.
Dermatomyositis (DM) is a rare autoimmune systemic disorder manifesting with typical skin rashes and proximal muscle weakness. A specific clinical DM subset is characterized by the presence of the anti-melanoma differentiation-associated protein 5 (MDA5) autoantibodies. These patients are usually burdened by a severe clinical phenotype exhibiting a poor prognosis. Interestingly, a growing body of evidence has shown that (interferon) IFN signature evaluation by the assessment of type I IFN score could be a possible mechanistic biomarker for these more severe patients with DM. Thus, in this work, the difference in type I IFN score between patients with DM and healthy controls (HCs), lacking systematic synthesis of available evidence, was assessed. Moreover, the possible difference in type I IFN score between patients with DM with or without MDA5 autoantibodies was investigated. A systematic review with a meta-analysis of available literature about values of type I IFN was performed in DM and HCs. A literature search was carried out in MEDLINE, SCOPUS, and WEB OF SCIENCE databases to identify all possible relevant studies published up to May 2024 in English language. Four studies met the inclusion criteria, comparing type I IFN score between patients with DM and HCs, or between patients with or without anti-MDA5 autoantibodies. The type I IFN score was significantly higher in patients affected by DM when compared with HCs (pooled SMD = 2.27; 95 % CI: 0.71, 3.82; p = 0.004, I2 = 96 %, pfor heterogeneity < 0.00001) and in patients with anti-MDA5 autoantibodies than those without (pooled SMD = 0.88; 95 % CI: 0.06, 1.70; p = 0.03, I2 = 83 %, pfor heterogeneity = 0.01). In this systematic review and meta-analysis, higher values of type I IFN score were retrieved in patients with DM when compared with HCs and in patients with anti-MDA5 autoantibodies with respect to those without. Thus, the assessment of type I IFN score appears to be a valuable mechanistic biomarker to clinically profile DM patients, and particularly those with anti-MDA5 autoantibodies.
Castellini C
，Scotti C
，Navarini L
，Fu Q
，Qian J
，Giacomelli R
，Cavagna L
，Ruscitti P
... -
《-》
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
... -
《-》
ResearchGate
(全网免费下载)
钛学术
(全网免费下载)
