Risk prediction modelling in idiopathic inflammatory myositis-associated interstitial lung disease based on seven factors including serum KL-6 and lung ultrasound B-lines.

OBJECTIVES: To develop a user-friendly nomogram-based predictive model for interstitial lung disease (ILD) in patients with idiopathic inflammatory myositis (IIM). METHODS: A retrospective study was conducted at Shantou Central Hospital, encompassing 205 IIM patients diagnosed between January 2013 and December 2022. We used the LASSO regression method in the discovery set to select features for model construction, followed by efficacy verification through AUC of ROC. Afterwards, KL-6 values and LUS B-lines number were added into this model to evaluate whether these 2 factors added to the model efficiency. Finally, a web version was constructed to make it more available. RESULTS: Among the 205 IIM patients, 115 (56.1%) patients were diagnosed with ILD, and 90 (43.9%) did not. The predictive model, derived from the training set, comprised four independent risk factors, including age, presence of respiratory symptoms, anti-melanoma differentiation-associated gene 5 (MDA-5) antibody positivity, and anti-aminoacyl transfer RNA synthetase (anti-ARS) antibodies positivity. Notably, anti-TIF1-γ antibody positivity emerged as a protective factor. The AUC of the ROC based on these 5 factors was 0.876 in the training set and 0.861 in the validation set. The AUC of the ROC based on the 5 factors plus KL-6 was 0.922, 5 factors plus B-line number was 0.949 and 5 factors plus both KL-6 and B-line number was 0.951. Accordingly, a nomogram and a web version were developed. CONCLUSIONS: This predictive model demonstrates robust capability to assess ILD risk in IIM patients, particularly when augmented with serum KL-6 level or/and LUS B-line number.

Application of logistic regression and machine learning methods for idiopathic inflammatory myopathies malignancy prediction.

OBJECTIVES: Malignancy is related to idiopathic inflammatory myopathies (IIM) and leads to a poor prognosis. Early prediction of malignancy is thought to improve the prognosis. However, predictive models have rarely been reported in IIM. Herein, we aimed to establish and use a machine learning (ML) algorithm to predict the possible risk factors for malignancy in IIM patients. METHODS: We retrospectively reviewed the medical records of 168 patients diagnosed with IIM in Shantou Central hospital, from 2013 to 2021. We randomly divided patients into two groups, the training sets (70%) for construction of the prediction model, and the validation sets (30%) for evaluation of model performance. We constructed six types of ML algorithms models and the AUC of ROC curves were used to describe the efficacy of the model. Finally, we set up a web version using the best prediction model to make it more generally available. RESULTS: According to the multi-variable regression analysis, three predictors were found to be the risk factors to establish the prediction model, including age, ALT<80U/L, and anti-TIF1-γ, and ILD was found to be a protective factor. Compared with five other ML algorithms models, the traditional algorithm logistic regression (LR) model was as good or better than the other models to predict malignancy in IIM. The AUC of the ROC using LR was 0.900 in the training set and 0.784 in the validation set. We selected the LR model as the final prediction model. Accordingly, a nomogram was constructed using the above four factors. A web version was built and can be visited on the website or acquired by scanning the QR code. CONCLUSIONS: The LR algorithm appears to be a good predictor of malignancy and may help clinicians screen, evaluate and follow up high-risk patients with IIM.

Predictive model of risk and severity of enteritis in systemic lupus erythematosus.

INTRODUCTION: To describe the clinical and laboratory features of systemic lupus erythematosus (SLE) enteritis and to establish a predictive model of risk and severity of lupus enteritis (LE). METHODS: Records of patients with SLE complaining about acute digestive symptoms were reviewed. The predictive nomogram for the diagnosis of LE was constructed by using R. The accuracy of the model was tested with correction curves. The receiver operating characteristic curve (ROC curve) program and a Decision curve analysis (DCA) were used for the verification of LE model. Receiver operating characteristic curve was also employed for evaluation of factors in the prediction of severity of LE. RESULTS: During the eight year period, 46 patients were in the LE group, while 32 were in the non-LE group. Abdominal pain, emesis, D-dimer >5 µg/mL, hypo-C3, and anti-SSA positive remained statistically significant and were included into the prediction model. Area under the curve (AUC) of ROC curve in this model was 0.909. Correction curve indicated consistency between the predicted rate and actual diagnostic rates. The DCA showed that the LE model was of benefit. Forty-four patients were included in developing the prediction model of LE severity. Infection, SLE disease activity index (SLEDAI), CT score, and new CT score were validated as risk factors for LE severity. The AUC of the combined SLEDAI, infection and new CT score were 0.870. CONCLUSION: The LE model exhibits good predictive ability to assess LE risk in SLE patients with acute digestive symptoms. The combination of SLEDAI, infection, and new CT score could improve the assessment of LE severity.

Pacific western boundary currents and their roles in climate.

Pacific Ocean western boundary currents and the interlinked equatorial Pacific circulation system were among the first currents of these types to be explored by pioneering oceanographers. The widely accepted but poorly quantified importance of these currents-in processes such as the El Niño/Southern Oscillation, the Pacific Decadal Oscillation and the Indonesian Throughflow-has triggered renewed interest. Ongoing efforts are seeking to understand the heat and mass balances of the equatorial Pacific, and possible changes associated with greenhouse-gas-induced climate change. Only a concerted international effort will close the observational, theoretical and technical gaps currently limiting a robust answer to these elusive questions.

Lung ultrasound B-lines and serum KL-6 correlate with the severity of idiopathic inflammatory myositis-associated interstitial lung disease.

OBJECTIVE: Idiopathic inflammatory myositis-associated interstitial lung disease (IIM-ILD) significantly increases morbidity and mortality. Lung ultrasound B-lines and Krebs von den Lungen-6 (KL-6) are identified as new sonographic and serum markers of ILD, respectively. The aim of our work was to assess the role of B-lines and KL-6 as markers of the severity of IIM-ILD. For this purpose, the correlation among B-lines score, serum KL-6 levels, high-resolution CT (HRCT) score, and pulmonary function tests were investigated in IIM-ILD patients. METHODS: Thirty-eight patients with IIM-ILD underwent chest HRCT scans, lung ultrasound and pulmonary function tests (independently performed within 1 week) examination. To assess severity and extent of ILD at HRCT, the Warrick score was used. The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 50 scanning sites. Serum KL-6 levels (U/ml) was measured by chemiluminescent enzyme immunoassay. RESULTS: A significant correlation was found between the B-lines score and serum KL-6 levels (r = 0.43, P < 0.01), and between the Warrick score and serum KL-6 levels (r = 0.45, P < 0.01). A positive correlation between B-lines score and the Warrick score (r = 0.87, P < 0.0001) was also confirmed. Both B-lines score and KL-6 levels inversely correlated to diffusion capacity for carbon monoxide (r = -0.77, P < 0.0001 and r = -0.42, P < 0.05, respectively) and total lung capacity (r = -0.73, P < 0.0001 and r = -0.36, P < 0.05, respectively). Moreover, B-lines correlated inversely with forced vital capacity (r = -0.73, P < 0.0001), forced expiratory volume in 1 s (r = -0.69, P < 0.0001). CONCLUSION: B-lines score and serum KL-6 levels correlate with HRCT findings and pulmonary function tests, supporting their use as measures of IIM-ILD severity.

Observed strengthening of interbasin exchange via the Indonesian seas due to rainfall intensification.

A proxy of the Indonesian Throughflow (ITF) transport, developed using in situ hydrographic measurements along with assimilations, shows a significant strengthening trend during the past decade. This trend is due to a freshening and subsequent increase in the halosteric component of the ITF transport associated with enhanced rainfall over the Maritime Continent over the same period. The strengthening of the ITF transport leads to a significant change in heat and freshwater exchange between the Pacific and Indian Oceans and contributes to the warming and freshening of the eastern Indian Ocean. The combined effect of the ITF transport of mass and freshwater along with tropical rainfall plays a very important role in the climate system.

Association of blood metals with serum sex hormones in adults: A cross-sectional study.

Heavy metals such as lead, mercury, and cadmium have been identified to have negative impacts on human health. Although the individual effects of these metals have been extensively researched, the present study aims to explore their combined effects and their association with serum sex hormones among adults. Data for this study were obtained from the general adult population of the 2013-2016 National Health and Nutrition Survey (NHANES) and included five metal (mercury, cadmium, manganese, lead, and selenium) exposures and three sex hormones (total testosterone [TT], estradiol [E2], and sex hormone-binding globulin [SHBG]) levels. The free androgen index (FAI) and TT/E2 ratio were also calculated. The relationships between blood metals and serum sex hormones were analysed using linear regression and restricted cubic spline regression. The effect of blood metal mixtures on sex hormone levels was examined using the quantile g-computation (qgcomp) model. There were 3,499 participants in this study, including 1,940 males and 1,559 females. In males, positive relationships between blood cadmium and serum SHBG (ß=0.049 [0.006, 0.093]), lead and SHBG (ß=0.040 [0.002, 0.079]), manganese and FAI (ß=0.080 [0.016, 0.144]), and selenium and FAI (ß=0.278 [0.054, 0.502]) were observed. In contrast, manganese and SHBG (ß=-0.137 [-0.237, -0.037]), selenium and SHBG (ß=-0.281 [-0.533, -0.028]), and manganese and TT/E2 ratio (ß=-0.094 [-0.158, -0.029]) were negative associations. In females, blood cadmium and serum TT (ß=0.082 [0.023, 0.141]), manganese and E2 (ß=0.282 [0.072, 0.493]), cadmium and SHBG (ß=0.146 [0.089, 0.203]), lead and SHBG (ß=0.163 [0.095, 0.231]), and lead and TT/E2 ratio (ß=0.174 [0.056, 0.292]) were positive relationships, while lead and E2 (ß=-0.168 [-0.315, -0.021]) and FAI (ß=-0.157 [-0.228, -0.086]) were negative associations. This correlation was stronger among elderly women (>50 years old). The qgcomp analysis revealed that the positive effect of mixed metals on SHBG was mainly driven by cadmium, while the negative effect of mixed metals on FAI was mainly driven by lead. Our findings indicate that exposure to heavy metals may disrupt hormonal homeostasis in adults, particularly in older women.

Serum B-cell activating factor and lung ultrasound B-lines in connective tissue disease related interstitial lung disease.

Objective: To investigate the role of serum B-cell activating factor (BAFF) and lung ultrasound (LUS) B-lines in connective tissue disease related interstitial lung disease (CTD-ILD), and their association with different ILD patterns on high resolution computed tomography (HRCT) of chest. Methods: We measured the levels of BAFF and KL-6 by ELISA in the sera of 63 CTD-ILD patients [26 with fibrotic ILD (F-ILD), 37 with non-fibrotic ILD (NF-ILD)], 30 CTD patients without ILD, and 26 healthy controls. All patients underwent chest HRCT and LUS examination. Results: Serum BAFF levels were significantly higher in CTD patients compared to healthy subjects (617.6 ± 288.1 pg/ml vs. 269.0 ± 60.4 pg/ml, p < 0.01). BAFF concentrations were significantly different between ILD group and non-ILD group (698.3 ± 627.4 pg/ml vs. 448.3 ± 188.6 pg/ml, p < 0.01). In patients with ILD, BAFF concentrations were significantly correlated with B-lines number (r = 0.37, 95% CI 0.13-0.56, p < 0.01), KL-6 level (r = 0.26, 95% CI 0.01-0.48, p < 0.05), and Warrick score (r = 0.33, 95% CI 0.09-0.53, p < 0.01), although all correlations were only low to moderate. B-lines number correlated with Warrick score (r = 0.65, 95% CI 0.48-0.78, p < 0.01), and KL-6 levels (r = 0.43, 95% CI 0.21-0.61, p < 0.01). Patients with F-ILD had higher serum BAFF concentrations (957.5 ± 811.0 pg/ml vs. 516.1 ± 357.5 pg/ml, p < 0.05), KL-6 levels (750.7 ± 759.0 U/ml vs. 432.5 ± 277.5 U/ml, p < 0.05), B-lines numbers (174.1 ± 82 vs. 52.3 ± 57.5, p < 0.01), and Warrick score (19.9 ± 4.6 vs. 13.6 ± 3.4, p < 0.01) vs. NF-ILD patients. The best cut-off values to separate F-ILD from NF-ILD using ROC curves were 408 pg/ml for BAFF (AUC = 0.73, p < 0.01), 367 U/ml for KL-6 (AUC = 0.72, p < 0.05), 122 for B-lines number (AUC = 0.89, p < 0.01), and 14 for Warrick score (AUC = 0.87, p < 0.01) respectively. Conclusion: Serum BAFF levels and LUS B-lines number could be useful supportive biomarkers for detecting and evaluating the severity and/or subsets of CTD-ILD. If corroborated, combining imaging, serological, and sonographic biomarkers might be beneficial and comprehensive in management of CTD-ILD.

[Research of progress of pyruvate dehydrogenase complex in sepsis metabolism].

Sepsis is a critical illness with high morbidity and mortality. Anaerobic glycolysis plays an important role in the pathogenesis of sepsis. Pyruvate dehydrogenase complex (PDHC) serves as a key regulator during sepsis. With PDHC dephosphorylation and deacetylation, PDHC activity is upregulated, allowing pyruvate translocate to mitochondria in aerobic condition, preceding the production of acetyl-CoA to accelerate aerobic oxidation. Activation of PDHC improves the prognosis of sepsis through regulating the balance of lactate, release of inflammatory factors and energy metabolism. A variety of remedies can improve the prognosis of patients with sepsis by up-regulating the activity of PDHC, including dichloroacetate (DCA), vitamin B1, milrinone, tumor necrosis factor binding protein, and ciprofloxacin.This article reviews the role and the regulatory mechanism of PDHC and signal pathway in the sepsis metabolism, in order to innovate treatment for sepsis and multiple organ dysfunction.

The role of lung ultrasound B-lines and serum KL-6 in the screening and follow-up of rheumatoid arthritis patients for an identification of interstitial lung disease: review of the literature, proposal for a preliminary algorithm, and clinical application to cases.

Screening and follow-up of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) is a challenge in clinical practice. In fact, the majority of RA-ILD patients are asymptomatic and optimal tools for early screening and regular follow-up are lacking. Furthermore, some patients may remain oligosymptomatic despite significant radiological abnormalities. In RA-ILD, usual interstitial pneumonia (UIP) is the most frequent radiological and pathological pattern, associated with a poor prognosis and a high risk to develop acute exacerbations and infections. If RA-ILD can be identified early, there may be an opportunity for an early treatment and close follow-up that might delay ILD progression and improve the long-term outcome.In connective tissue disease-associated interstitial lung disease (CTD-ILD), lung ultrasound (LUS) with the assessment of B-lines and serum Krebs von den Lungen-6 antigen (KL-6) has been recognized as sensitive biomarkers for the early detection of ILD. B-line number and serum KL-6 level were found to correlate with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and other clinical parameters in systemic sclerosis-associated ILD (SSc-ILD). Recently, the significant correlation between B-lines and KL-6, two non-ionizing and non-invasive biomarkers, was demonstrated. Hence, the combined use of LUS and KL-6 to screen and follow up ILD in RA patients might be useful in clinical practice in addition to existing tools. Herein, we review relevant literature to support this concept, propose a preliminary screening algorithm, and present 2 cases where the algorithm was used.

Deep-reaching acceleration of global mean ocean circulation over the past two decades.

Ocean circulation redistributes Earth's energy and water masses and influences global climate. Under historical greenhouse warming, regional ocean currents show diverse tendencies, but whether there is an emerging trend of the global mean ocean circulation system is not yet clear. Here, we show a statistically significant increasing trend in the globally integrated oceanic kinetic energy since the early 1990s, indicating a substantial acceleration of global mean ocean circulation. The increasing trend in kinetic energy is particularly prominent in the global tropical oceans, reaching depths of thousands of meters. The deep-reaching acceleration of the ocean circulation is mainly induced by a planetary intensification of surface winds since the early 1990s. Although possibly influenced by wind changes associated with the onset of a negative Pacific decadal oscillation since the late 1990s, the recent acceleration is far larger than that associated with natural variability, suggesting that it is principally part of a long-term trend.

Tropical Meridional Overturning Circulation Observed by Subsurface Moorings in the Western Pacific.

Meridional ocean current in the northwestern Pacific was documented by seven subsurface moorings deployed at 142°E during August 2014-October 2015. A sandwich structure of the tropical meridional overturning circulation (TMOC) was revealed between 0-6°N that consists of a surface northward flow (0-80 m), a thermocline southward flow (80-260 m; 22.6-26.5 σ θ ), and a subthermocline northward flow (260-500 m; 26.5-26.9 σ θ ). Based on mooring data, along with satellite and reanalysis data, prominent seasonal-to-interannual variations were observed in all three layers, and the equatorial zonal winds were found to be a dominant cause of the variations. The TMOC is generally stronger in boreal winter and weaker in summer. During 2014-2015, the TMOC was greatly weakened by westerly wind anomalies associated with the El Niño condition. Further analysis suggests that the TMOC can affect equatorial surface temperature in the western Pacific through anomalous upwelling/downwelling and likely plays a vital role in the El Niño-Southern Oscillation (ENSO).

Structure and Variability of the North Equatorial Current/Undercurrent from Mooring Measurements at 130°E in the Western Pacific.

The mean structure and variability of the North Equatorial Current/Undercurrent (NEC/NEUC) are investigated with one-year Acoustic Doppler Current Profilers measurements from 4 subsurface moorings deployed at 10.5°N, 13°N, 15.5°N, and 18°N along 130°E in the western Pacific. The strong westward flowing NEC ranges from the sea surface down to 400 m, and the mean zonal velocity of the NEC at 10.5°N is around -30 cm/s at the depth of 70 m. Eastward flowing NEUC jets are detected below the NEC at 10.5°N and 13°N, and the depth of the NEUC could reach at least 900 m. The mean velocity of the NEUC is around 4.2 cm/s at 800 m. No eastward undercurrents are observed at 15°N and 18°N. The mooring measurements also reveal a strong intraseasonal variability of the currents at all 4 mooring sites, and the period is around 70-120 days. The vertical structure of this intraseasonal variability varies at different latitudes. The variability of the NEUC jets at 10.5°N and 13°N appears to be dominated by subthermocline signals, while the variability of the currents at 15.5°N and 18°N is dominated by surface-intensified signals.