Safety of prolonged use of metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis.

Background: Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). Methods: A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25-80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. Results: Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. Conclusions: Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

Dynamic shifts in lung cytokine patterns in post-COVID-19 interstitial lung disease patients: a pilot study.

Introduction: The pathogenesis of post-COVID interstitial lung disease, marked by lung tissue scarring and functional decline, remains largely unknown. Objectives: We aimed to elucidate the temporal cytokine/chemokine changes in bronchoalveolar lavage (BAL) from patients with post-COVID interstitial lung disease to uncover potential immune drivers of pulmonary complications. Design: We evaluated 16 females diagnosed with post-COVID interstitial lung disease, originating from moderate to severe cases during the second epidemic wave in the Autumn of 2020, treated at the Pneumology Department of the Arad County Clinical Hospital, Romania. Their inflammatory response over time was compared to a control group. Methods: A total of 48 BAL samples were collected over three intervals (1, 3, and 6 months) and underwent cytology, gene, and protein expression analyses for pro/anti-inflammatory lung cytokines and chemokines using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results: One month after infection, there were significant increases in the levels of IL-6 and IL-8. These levels decreased gradually over the course of 6 months but were still higher than those seen in control. Interferon-gamma and tumor necrosis factor alpha exhibited similar patterns. Persistent elevations were found in IL-10, IL-13, and pro-fibrotic M2 macrophages' chemokines (CCL13 and CCL18) for 6 months. Furthermore, pronounced neutrophilia was observed at 1 month post-COVID, highlighting persistent inflammation and lung damage. Neutrophil efferocytosis, aiding inflammation resolution and tissue repair, was evident at the 1-month time interval. A notable time-dependent reduction in CD28 was also noticed. Conclusion: Our research provides insight into the immunological processes that may lead to the fibrotic changes noted in the lungs following COVID-19.

BACKGROUND: Post-COVID lung disease represents a significant health concern that demands comprehensive research. The pathogenesis of post-COVID interstitial lung disease, marked by lung tissue scarring and functional decline, remains largely unknown. METHODS: We evaluated 16 females diagnosed with post-COVID interstitial lung disease, originating from moderate to severe cases during the second epidemic wave in the Autumn 2020, treated at the Pneumology Department of the Arad County Clinical Hospital, Romania. Their inflammatory response over time was compared to a control group. A total of 48 BAL samples were collected over three intervals (1, 3, and 6 months) and underwent cytology, gene, and protein expression analyses for pro/anti-inflammatory lung cytokines and chemokines using RT-PCR and ELISA The interrelationships between the expression levels of various pro-inflammatory and anti-inflammatory cytokines and chemokines by Pearson's correlations was investigated. RESULTS: One month after infection, there were significant increases in the levels of IL-6 and IL-8. These levels decreased gradually over the course of six months but were still higher than those seen in control. IFN-γ and TNF-α exhibited similar patterns. Persistent elevations were found in IL-10, IL-13, and pro-fibrotic M2 macrophages' chemokines (CCL13 and CCL18) for six months. Pronounced neutrophilia was observed at 1 month post-COVID, highlighting persistent inflammation and lung damage. Neutrophils efferocytosis, aiding inflammation resolution and tissue repair, was evident at the 1-month time-interval. A notable time-dependent reduction in CD28 was also noticed. CONCLUSIONS: Our research provides insight into the immunological processes that may lead to the fibrotic changes noted in the lungs following COVID-19.

Dynamic shifts in lung cytokine patterns in post-COVID-19 interstitial lung disease patients: a pilot study The objective of this pilot study was to investigate changes in lung cytokine pro- and anti-inflammatory profiles among patients with interstitial lung disease after COVID-19 infection.

Identification and validation of mutual hub genes in idiopathic pulmonary fibrosis and rheumatoid arthritis-associated usual interstitial pneumonia.

Objectives: The study aims at exploring common hub genes and pathways in idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) through integrated bioinformatics analyses. Methods: The GSE199152 dataset containing lung tissue samples from IPF and RA-UIP patients was acquired from the Gene Expression Omnibus (GEO) database. The identification of overlapping differentially expressed genes (DEGs) in IPF and RA-UIP was carried out through R language. Protein-protein interaction (PPI) network analysis and module analysis were applied to filter mutual hub genes in the two diseases. Enrichment analyses were also conducted to analyze the possible biological functions and pathways of the overlapped DEGs and hub genes. The diagnostic value of key genes was assessed with R language, and the expressions of these genes in pulmonary cells of IPF and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients were analyzed with single cell RNA-sequencing (scRNA-seq) datasets. The expression levels of hub genes were validated in blood samples from patients, specimens of human lung fibroblasts, lung tissue samples from mice, as well as external GEO datasets. Results: Four common hub genes (THBS2, TIMP1, POSTN, and CD19) were screened. Enrichment analyses showed that the abnormal expressions of DEGs and hub genes may be connected with the onset of IPF and RA-UIP by regulating the progression of fibrosis. ScRNA-seq analyses illustrated that for both IPF and RA-ILD patients, THBS2, TIMP1, and POSTN were mainly expressed in lung fibroblasts, while CD19 was uniquely high-expressed in B cells. The qRT-PCR and immunohistochemistry (IHC) results verified that the expression levels of hub genes were mostly in accordance with the findings obtained from the bioinformatics analyses. Conclusion: Though IPF and RA-UIP are distinct diseases, they may to some extent have mutual pathogenesis in the development of fibrosis. THBS2, TIMP1, POSTN, and CD19 may be the potential biomarkers of IPF and RA-UIP, and intervention on related pathways of these genes could offer new strategies for the precision treatment of IPF and RA-UIP.

Systemic juvenile idiopathic arthritis-associated lung disease: A retrospective cohort study.

BACKGROUND: Lung damage in systemic juvenile arthritis (sJIA) is one of the contemporary topics in pediatric rheumatology. Several previous studies showed the severe course and fatal outcomes in some patients. The information about interstitial lung disease (ILD) in the sJIA is scarce and limited to a total of 100 cases. AIM: To describe the features of sJIA patients with ILD in detail. METHODS: In the present retrospective cohort study, information about 5 patients less than 18-years-old with sJIA and ILD were included. The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019. ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement. Macrophage activation syndrome (MAS) was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement. RESULTS: The onset age of sJIA ranged from 1 year to 10 years. The time interval before ILD ranged from 1 mo to 3 years. The disease course was characterized by the prevalence of the systemic features above articular involvement, intensive rash (100%), persistent and very active MAS (hScore range: 194-220) with transaminitis (100%), and respiratory symptoms (100%). Only 3 patients (60%) developed a clubbing phenomenon. All patients (100%) had pleural effusion and 4 patients (80%) had pericardial effusion at the disease onset. Two patients (40%) developed pulmonary arterial hypertension. Infusion-related reactions to tocilizumab were observed in 3 (60%) of the patients. One patient with trisomy 21 had a fatal disease course. Half of the remaining patients had sJIA remission and 2 patients had improvement. Lung disease improved in 3 patients (75%), but 1 of them had initial deterioration of lung involvement. One patient who has not achieved the sJIA remission had the progressed course of ILD. No cases of hyper-eosinophilia were noted. Four patients (80%) received canakinumab and one (20%) tocilizumab at the last follow-up visit. CONCLUSION: ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset. Extensive rash, serositis (especially pleuritis), full-blown MAS with transaminitis, lymphopenia, trisomy 21, eosinophilia, and biologic infusion reaction are the main predictors of ILD. The following studies are needed to find the predictors, pathogenesis, and treatment options, for preventing and treating the ILD in sJIA patients.

Significance of preoperative exercise oxygen desaturation in lung cancer with interstitial lung disease.

OBJECTIVES: Evaluating the diffusing capacity for carbon monoxide (DLco) is crucial for patients with lung cancer and interstitial lung disease. However, the clinical significance of assessing exercise oxygen desaturation (EOD) remains unclear. METHODS: We retrospectively analyzed 186 consecutive patients with interstitial lung disease who underwent lobectomy for non-small cell lung cancer. EOD was assessed using two-flight test (TFT), with TFT positivity defined as ≥ 5% SpO2 reduction. We investigated the impact of EOD and predicted postoperative (ppo) %DLco on postoperative complications and prognosis. RESULTS: A total of 106 (57%) patients were identified as TFT-positive, and 58 (31%) patients had ppo% DLco < 30%. Pulmonary complications were significantly more prevalent in TFT-positive patients than in TFT-negative patients (52% vs 19%, P < 0.001), and multivariable analysis revealed that TFT-positivity was an independent risk factor (odds ratio 3.46, 95% confidence interval 1.70-7.07, P < 0.001), while ppo%DLco was not (P = 0.09). In terms of long-term outcomes, both TFT positivity and ppo%DLco < 30% independently predicted overall survival. We divided the patients into four groups based on TFT positivity and ppo%DLco status. TFT-positive patients with ppo%DLco < 30% exhibited the significantly lowest 5-year overall survival among four groups: ppo%DLco ≥ 30% and TFT-negative, 54.2%; ppo%DLco < 30% and TFT-negative, 68.8%; ppo%DLco ≥ 30% and TFT-positive, 38.1%; and ppo%DLco < 30% and TFT-positive, 16.7% (P = 0.001). CONCLUSIONS: Incorporating EOD evaluation was useful for predicting postoperative complications and survival outcomes in patients with lung cancer and interstitial lung disease.

Evaluating Sensitization-Associated, Neuropathic-Like Symptoms and Psychological Factors in Patients with Interstitial Lung Disease.

The aims of this study were to phenotype pain in patients with interstitial lung disease (ILD) by investigating the association between sensitization-associated symptoms with quality of life, anxiety/depression, pain catastrophizing and kinesiophobia levels, and, identifying those risk factors explaining the variance of quality of life in individuals with ILD and pain. One hundred and thirty-two (38.6% women, mean age: 70, SD: 10.5 years) patients with ILD completed clinical (age, sex, height, weight), psychological (Hospital Anxiety and Depression Scale, HADS and the Pittsburgh Sleep Quality Index, PSQI), and health-related quality of life (EQ-5D-5L) variables as well as the Central Sensitization Inventory (CSI), the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), Pain Catastrophizing Scale (PCS) and Tampa Scale for Kinesiophobia (TSK-11) questionnaires. The prevalence of sensitization-associated symptomatology (CSI), neuropathic-like features (S-LANSS), anxiety symptoms, depressive symptoms or poor sleep was 20.5%, 23.5%, 23.6%, 22.9% or 51.6%. Significant associations between CSI, S-LANSS, HADS-A, HADS-D, PCS, TSK-11 and EQ-5D-5L (.220

Development of anti-MDA5 autoantibody-positive dermatomyositis following the use of etanercept biosimilar in rheumatoid arthritis.

The induction of autoimmune diseases during tumor necrosis factor-alpha inhibitor (TNFi) usage has been described. Herein, we report a rare case of a 49-year-old woman with anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive dermatomyositis (DM), which developed five weeks after the introduction of an etanercept biosimilar to rheumatoid arthritis (RA). Four of the five known cases, including ours, of anti-MDA5Ab positive DM complicated with RA revealed anti-MDA5Ab positive DM following TNFi usage. When patients with RA are diagnosed with interstitial lung disease during TNFi usage, anti-MDA5 Ab-positive DM could be a differential diagnosis.

Experiences of systemic sclerosis patients with home monitoring of their pulmonary function: a qualitative study.

Objective: To evaluate the experiences, perceived benefits and disadvantages of home monitoring of pulmonary function in SSc patients with interstitial lung disease (ILD). Methods: Semistructured interviews were conducted among SSc-ILD patients who used the home monitoring application of pulmonary function for at least 3 months. In our program, patients are instructed to perform home spirometry weekly at fixed time points using a mobile application with results being directly visible for patients and physicians. Audiotapes of the interviews were transcribed verbatim and analysed using inductive thematic analysis after performing a member check. Results: A total of 13 patients were interviewed, with a median age of 58 years (range 36-75) and a median experience with home monitoring of 12 months (range 3-12). We identified four major themes, including routine of telemonitoring, impact of telemonitoring, trust in telemonitoring and implementation in regular healthcare. Overall, patients found performing home spirometry to be feasible. Major perceived benefits of performing home spirometry are an increase in patient empowerment, better understanding of the disease course and a reduction in hospital visits, whereas identified disadvantages are an emotional burden of telemonitoring, heightened awareness of illness, doubts about its validity and the need for digital competencies. All patients expressed their willingness to continue, although some patients emphasized the need for face-to-face visits. Conclusion: Telemonitoring of pulmonary function is accepted by SSc-ILD patients with the perceived benefits outweighing the disadvantages. Adopting a patient-centred strategy that considers individual factors and addresses concerns proactively is warranted to successfully implement home spirometry.

Eating and drinking experience in patients with idiopathic pulmonary fibrosis: a qualitative study.

OBJECTIVE: To explore eating and drinking experiences of patients with idiopathic pulmonary fibrosis (IPF), the impact of any changes associated with their diagnosis and any coping mechanisms developed by patients. SETTING: Pulmonary fibrosis support groups around the UK and the regional Interstitial Lung Diseases Clinic, Newcastle upon Tyne. PARTICIPANTS: 15 patients with IPF (9 men, 6 women), median age 71 years, range (54-92) years, were interviewed. Inclusion criteria included competent adults (over the age of 18 years) with a secure diagnosis of IPF as defined by international consensus guidelines. Patients were required to have sufficient English language competence to consent and participate in an interview. Exclusion criteria were a history of other lung diseases, a history of pre-existing swallowing problem of other causes that may be associated with dysphagia and individuals with significant communication or other memory difficulties that render them unable to participate in an interview. DESIGN: A qualitative study based on semistructured interviews used purpose sampling conducted between February 2021 and November 2021. Interviews were conducted via video videoconferencing call platform or telephone call, transcribed and data coded and analysed using a reflexive thematic analysis. RESULTS: Three main themes were identified, along with several subthemes, which were: (1) Eating, as such, is no longer a pleasure. This theme mainly focused on the physical and sensory changes associated with eating and drinking and their effects and the subsequent emotional and social impact of these changes; (2) It is something that happens naturally and just try and get on with it. This theme centred on the self-determined strategies employed to manage changes to eating and drinking; and (3) What is normal. This theme focused on patients seeking information to better understand the changes in their eating and drinking and the patients' beliefs about what has changed their eating and drinking. CONCLUSIONS: To our knowledge, this is the first study to report on IPF patients' lived experience of eating and drinking changes associated with their diagnosis. Findings demonstrate that some patients have substantial struggles and challenges with eating and drinking, affecting them physically, emotionally and socially. There is a need to provide better patient information for this area and further study.

A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. CASE PRESENTATION: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. CONCLUSIONS: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.

Risk of interstitial lung disease with the use of programmed cell death 1 (PD-1) inhibitor compared with programmed cell death ligand 1 (PD-L1) inhibitor in patients with breast cancer: A systematic review and meta-analysis.

Background: Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have become integral elements within the current landscape of breast cancer treatment modalities; however, they are associated with interstitial lung disease (ILD), which is rare but potentially fatal. Notably, only a few studies have compared the difference in ILD incidence between PD-1 and PD-L1 inhibitors. Therefore, this study aimed to assess the discrepancies regarding ILD risk between the two immune checkpoint inhibitors. We also reported three cases of ILD after PD-1 inhibitor treatment. Methods: We comprehensively searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that investigated PD-1/PD-L1 inhibitor treatment for patients with breast cancer. Pooled overall estimates of incidence and risk ratio (RR) were calculated with a 95% confidence interval (CI), and a mirror group analysis was performed using eligible studies. Results: This meta-analysis included 29 studies with 4639 patients who received PD-1/PD-L1 inhibitor treatment. A higher ILD incidence was observed among 2508 patients treated with PD-1 inhibitors than among 2131 patients treated with PD-L1 inhibitors (0.05 vs. 0.02). The mirror group analysis further revealed a higher ILD event risk in patients treated with PD-1 inhibitors than in those treated with PD-L1 inhibitors (RR = 2.34, 95% CI, 1.13-4.82, P = 0.02). Conclusion: Our findings suggest a greater risk of ILD with PD-1 inhibitors than with PD-L1 inhibitors. These findings are instrumental for clinicians in treatment deliberations, and the adoption of more structured diagnostic approaches and management protocols is necessary to mitigate the risk of ILD.

Clinical utility, reproducibility, and radiologist acceptance of ILD-RADS.

PURPOSE: To investigate the clinical utility, reproducibility, and radiologists' acceptance of the Interstitial Lung Disease Imaging-Reporting and Data System (ILD-RADS). METHOD: In this single-institutional retrospective study, three radiologists independently reviewed the chest high-resolution CT (HRCT) scans of 111 consecutive patients diagnosed with ILDs. They assessed the HRCT pulmonary features using the ILD-RADS template and assigned an ILD-RADS category (1-4) to each scan based on the identified imaging pattern. Patients were classified into idiopathic pulmonary fibrosis (IPF) (n = 14) and non-IPF ILD (n = 97) groups based on clinical diagnoses determined by multidisciplinary discussion. Association between ILD-RADS categories and clinical diagnoses was assessed using the Chi-square test for trend. Reproducibility was evaluated using kappa (k) scores, and radiologists' acceptance of the ILD-RADS was evaluated with a questionnaire. RESULTS: We found a significant association between the ILD-RADS categories and patients' clinical diagnoses (P ≤ 0.0001) for the three readers, with a trend toward increased assignment of ILD-RADS-1 to IPF patients (50 %-57.1 %), and ILD-RADS-4 to non-IPF patients (46.4 %-49.5 %). The ILD-RADS categories showed excellent intra-reader agreement (k = 0.873) and moderate inter-reader agreement (k = 0.440). ILD-RADS-1 and -4 categories showed the highest inter-reader agreement (k = 0.681 and 0.481, respectively). Radiologists gave a positive response to using the ILD-RADS in daily practice. CONCLUSIONS: The clinical utility of the ILD-RADS was demonstrated by the significant association between the ILD-RADS categories and patients' clinical diagnoses, particularly the ILD-RADS-1 and -4 categories. Excellent intra-reader and moderate inter-reader reproducibility was observed. ILD-RADS has the potential to be widely accepted for standardized HRCT reporting among radiologists.

Diagnostic Value of Krebs von den Lungen (KL-6) for Interstitial Lung Disease: A European Prospective Cohort.

INTRODUCTION: Krebs von den Lungen 6 (KL-6) is a mucin-1 glycoprotein produced by type II pneumocytes. High levels of KL-6 in blood may be found in patients with lung fibrosis. In Asia this biomarker is used for diagnosis and prognosis in interstitial lung diseases (ILD). There is a lack of information regarding KL-6 cut-off point for diagnosis and prognosis in European population. The aim of this study was to establish the cut-off point for serum KL-6 associated with the presence of ILD in the Spanish population. METHODS: Prospective study including subjects who underwent chest HRCT, PFTs and autoimmune blood analysis. Two groups were created: non-ILD subjects and ILD patients. Serum KL-6 concentrations were measured using a Lumipulse KL-6 reagent assay and the optimal cut-off value was evaluated by a ROC analysis. Data on demographics and smoking history was also collected. RESULTS: One hundred seventy-nine patients were included, 102 with ILD. Median serum KL-6 values overall were 762U/mL, 1080 (±787)U/mL for the ILD group vs 340 (±152)U/mL for the non-ILD group (p<0.0001). The main radiological pattern was NSIP (43%). ROC analysis showed greater specificity (86%) and sensitivity (82%) for KL-6 465U/mL for detecting ILD patients. The multivariate logistic regression model pointed to the male sex, higher KL-6 values, lower FVC and low DLCO values as independent factors associated with ILD. CONCLUSION: Serum KL-6 values greater than 465U/mL have excellent sensitivity and specificity for detecting ILD in our Spanish cohort. Multicentre studies are needed to validate our results.

Divergent perspectives: exploring the relationships between St. George's Respiratory Questionnaire and outcome measures in systemic sclerosis-associated interstitial lung disease.

INTRODUCTION/OBJECTIVES: Controversy exists regarding the concordance of patient-reported outcome measures (PROMs) with other assessment parameters in systemic sclerosis-associated interstitial lung disease (SSc-ILD). This study aims to explore the association between the St. George's Respiratory Questionnaire (SGRQ) and various outcome measures in patients with SSc-ILD within a real-world cross-sectional setting. METHOD: Patients with SSc-ILD were consecutively recruited from our SSc cohort. Simultaneous administration of SGRQ, scleroderma Health Assessment Questionnaire (sHAQ), respiratory visual analog scale (R-VAS), pulmonary function tests (PFTs), and the 6-min walking test (6-MWT) was conducted. The total extent of lung fibrosis was quantified using high-resolution computed tomography (HRCT) images. Relationships between SGRQ and functional, radiographic, and other patient-reported outcome measures were analyzed. RESULTS: The total SGRQ score demonstrated correlations with forced vital capacity (FVC) and R-VAS (r = - 0.397, p = 0.016 and r = 0.418, p = 0.027, respectively). Symptom score correlated with ILD-extension (r = 0.430, p = 0.005); activity score correlated with FVC and R-VAS (r = - 0.502, p = 0.002 and r = 0.395, p = 0.038, respectively); impact score correlated with R-VAS (r = 0.386, p = 0.043). In patients with fibrosis extent exceeding 20%, total SGRQ score was associated with sHAQ and R-VAS (r = 0.398, p = 0.049; r = 0.524, p = 0.021, respectively), activity score with R-VAS (r = 0.478, p = 0.038), and impact score with 6-MWT-D and R-VAS (r = - 0.489, p = 0.034; r = 0.545, p = 0.016, respectively). The symptom score and activity score demonstrated optimal performance in identifying patients with interstitial lung disease (ILD) extent exceeding 20% and forced vital capacity (FVC) less than 70% (area under the curve [AUC] 0.799, p = 0.002, and AUC 0.792, p = 0.03, respectively). CONCLUSIONS: Our study reveals varying degrees of correlation between SGRQ and distinct outcome measures. Given the incomplete alignment of SGRQ with other outcome measures, an integrative approach utilizing existing criteria as complementary tools is recommended. Key Points • Patient-reported outcome measures (PROMs) derive from patients' subjective evaluations of the impact of the disease on their daily activities, social interactions, and psychological well-being. • PROMs frequently serve as outcome measures in randomized controlled trials, yet conflicting findings have emerged in relation to primary outcomes. • This study aims to assess the appropriateness and interrelation of PROMs with both radiological and functional outcome measures, providing insight into the current state of our patients in a real-life context. The investigation delves into the compatibility of these measures with each other.

Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Weight loss with GLP-1 analogues in preparation for transplantation.

This case describes a woman in her 20s with a 6-month history of progressive exertional dyspnoea and cough. Examination revealed hypoxia on room air, sinus tachycardia, finger clubbing and bibasal inspiratory crackles. Inflammatory markers were mildly elevated and empirical antimicrobial therapy was commenced. A multidisciplinary discussion consensus diagnosis of acute interstitial pneumonitis was made based on the findings of high-resolution CT of the chest, macrophage predominant bronchoalveolar lavage cell differential and surgical lung biopsy. There was clinical and radiological deterioration despite glucocorticoids and antifibrotic therapy. A body mass index of 37.5 kg/m2 precluded her from lung transplant assessment and consideration. Following consultation with the weight management service, she was commenced on glucagon-like peptide 1 (GLP-1) analogue therapy. She had a remarkable response within 6 months, was listed for lung transplantation, and within 18 months of her initial presentation, a double lung transplantation was performed.

Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis.

Introduction: We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). Methods: Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493. Results: According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events. Discussion: In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.