Diffuse Disease Research Articles

Subendocardial ischemia: does CMD really exist?

Patients with angina but without obstructive epicardial coronary disease still require a specific mechanistic diagnosis to enable targeted treatment. The overarching term "coronary microvascular dysfunction" (CMD) has been applied broadly - but is it correct? We present a series of case examples culminating a systematic exploration of our large clinical database to distinguish among four categories of coronary pathophysiology. First, by far the largest group of "no stenosis angina" patients exhibits subendocardial ischemia during intact flow through diffuse epicardial disease during dipyridamole vasodilator stress. Second, rare patients indeed have ischemic signs or symptoms due solely to reduced flow attributable to microvascular dysfunction but without subendocardial hypoperfusion. Third, a previously unrecognized group of patients displays significant ST-segment changes and rare angina but normal high dipyridamole induced coronary flow and intact normal subendocardial uptake, perhaps due to a stretch mechanism from hyperemia. Fourth, ischemia due to reduced flow plus a subendocardial defect can arise as a secondary effect of a variety of global cardiac pathology, for example severe diffuse atherosclerosis, severe aortic stenosis, or a primary cardiomyopathy. Because subendocardial ischemia dominates the pathophysiologic epidemiology of these patient categories, understanding its mechanisms and therefore potential treatment targets will bring the largest clinical benefits to the largest number of patients. However, its diagnosis requires meticulous attention to exclude caffeine that can lead to a "false positive" diagnosis of CMD, absolute flow quantification to avoid confusing high resting flow with normal stress flow from reduced flow capacity, and quantification of subendocardial blood flow.

Diffuseness of coronary artery disease impacts on immediate hemodynamic and predicted clinical outcomes

Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial. The pathophysiological pattern of CAD was defined as “predominantly diffuse” or “focal” according to a virtual QFR pullback pressure gradient (PPG) index < 0.78 and ≥ 0.78, respectively. Physiological “focal severity” was assessed using the QFR gradient per mm (dQFR/ds), with a value ≥ 0.025/mm the threshold for a “major gradient”. A post-PCI QFR ≥ 0.91 was considered optimal. Median pre-PCI PPG index was 0.70 (IQR 0.59–0.80). The prevalence of “predominantly diffuse” CAD and “major gradient” were 68.6% and 85.8%, respectively. A “Predominantly diffuse” pattern with a major gradient had a higher risk of a post-PCI QFR < 0.91 (OR 1.52,95%CI 1.47–1.58). In multivariable analysis, low QFR PPG index (diffuse disease) was an independent determinant of a post-PCI QFR < 0.91 (per 0.1 decrease of QFR PPG index, OR:9.8, 95% CI 3.0–32.2, p < 0.001). Based on post-PCI QFR the predicted 2-year VOCE, a powered endpoint in the MVT trial, was 6.1% and 4.2% in diffuse and focal lesions, respectively. A pre-procedure physiological pattern of diffuse CAD is an independent determinant of an unfavourable immediate hemodynamic outcome post-PCI, and detrimentally affects the predicted 2-year VOCE.Clinical Trial Registration URL: https://www.clinicaltrials.gov/ct2/show/NCT04390672Unique Identifier: NCT04390672 (registration date 15/05/2020)

Evaluating the Diagnostic Value of Lymphocyte Subsets in Bronchoalveolar Lavage Fluid and Peripheral Blood Across Various Diffuse Interstitial Lung Disease Subtypes.

Diffuse interstitial lung diseases (ILD) include conditions with identifiable causes such as chronic eosinophilic pneumonia (CEP), sarcoidosis (SAR), chronic hypersensitivity pneumonitis (CHP), and connective tissue disease-associated interstitial pneumonia (CTD), as well as idiopathic interstitial pneumonia (IIP) of unknown origin. In non-IIP diffuse lung diseases, bronchoalveolar lavage (BAL) fluid appearance is diagnostic. This study examines lymphocyte subsets in BAL fluid and peripheral blood of 56 patients with diffuse ILD, excluding idiopathic pulmonary fibrosis (IPF), who underwent BAL for diagnostic purposes. Patients were classified into CEP, SAR, CHP, CTD, and IIP groups, and clinical data, BAL cell analysis, and peripheral blood mononuclear cell analysis were compared. Eosinophils and type 3 innate lymphocytes (ILC3s) were significantly increased in the BAL fluid of the CEP group. Receiver operating characteristic curve analysis identified eosinophils ≥ 8% in BAL cells and ILC3s ≥ 0.0176% in the BAL lymphocyte fraction as thresholds distinguishing CEP. SAR patients exhibited significantly elevated CD4/CD8 ratios in the BAL fluid, with a ratio of 3.95 or higher and type 1 innate lymphoid cell frequency ≥ 0.254% as differentiation markers. High Th1 cell frequency (≥17.4%) in BAL lymphocytes in IIP, elevated serum KL-6 (≥2081 U/mL) and SP-D (≥261 ng/mL) in CHP, and increased BAL neutrophils (≥2.0%) or a low CD4/CD8 ratio (≤1.2) in CTD serve as distinguishing markers for each ILD. Excluding CEP and SAR, CD4+ T cell frequencies, including Th1, Th17, and Treg cells in peripheral blood, may differentiate IIP, CHP, and CTD.

Impact of Warfarin and Dual Antiplatelet Therapy on Graft Failure After Coronary Endarterectomy: A Retrospective Cohort Study.

Coronary endarterectomy combined with coronary artery bypass grafting (CE-CABG) effectively achieves coronary revascularization in patients with diffuse atherosclerotic coronary artery disease (CAD). However, the loss of the subendothelial tissue at the CE-CABG coronary artery accelerates local thrombosis, leading to CE-CABG graft failure. Dual antiplatelet therapy (DAT) and warfarin plus aspirin (WPA) are the two most common anticoagulation strategies post CE-CABG. This retrospective study compares the clinical outcomes and graft failure rates associated with these two approaches. This study is a retrospective cohort study. Between July 2016 and April 2024, 102 patients with diffuse CAD underwent CE-CABG. Six patients were excluded. In total, 96 patients (mean age 59.8 ± 7.7years) enrolled in the study (43 in DAT group and 53 in WPA group). The DAT group received aspirin (100mg, qd) and clopidogrel (75mg, qd) for 1 year postoperatively, transitioning to aspirin (100mg, qd) after 1 year. The WPA group received warfarin (international normalized ratio, INR remained at 1.8-2.5) and aspirin (100mg, qd) for 3 months postoperatively, followed by DAT after 3 months, changed to aspirin monotherapy after 1year. The primary endpoint was graft failure of the CE-CABG graft. Four patients died during the perioperative period (1 in DAT group, 3 in WPA group), resulting in an overall perioperative mortality rate of 4.2%. Five patients were lost for follow-up. Mean follow-up time was 38months. Three patients died during the follow-up period (1 in DAT group, 2 in WPA group). The CE-CABG graft patency of the WPA group was significantly higher compared to the DAT group (88.1% vs. 50.0%, P < 0.001). Kaplan-Meier analysis showed that the median graft failure time was significantly longer in the WPA group (77months, 95% CI 69-85) compared to the DAT group (73months, 95% CI 17-129, P = 0.017). A higher proportion of the DAT group was classified as NYHA III-IV compared to the WPA group (26.2% vs. 10.2%, P = 0.046). One patient of the WPA group had a gastrointestinal bleeding event, and the overall incidence of bleeding events was not statistically different between the two groups. Using the WPA strategy after CE-CABG significantly reduces the rate of graft failure and improves cardiac function without increasing the risk of bleeding events.

The bronchoalveolar lavage fluid CD44 as a marker for pulmonary fibrosis in diffuse parenchymal lung diseases.

Diffuse parenchymal lung diseases (DPLD) cover heterogeneous types of lung disorders. Among many pathological phenotypes, pulmonary fibrosis is the most devastating and represents a characteristic sign of idiopathic pulmonary fibrosis (IPF). Despite a poor prognosis brought by pulmonary fibrosis, there are no specific diagnostic biomarkers for the initial development of this fatal condition. The major hallmark of lung fibrosis is uncontrolled activation of lung fibroblasts to myofibroblasts associated with extracellular matrix deposition and the loss of both lung structure and function. Here, we used this peculiar feature in order to identify specific biomarkers of pulmonary fibrosis in bronchoalveolar lavage fluids (BALF). The primary MRC-5 human fibroblasts were activated with BALF collected from patients with clinically diagnosed lung fibrosis; the activated fibroblasts were then washed rigorously, and further incubated to allow secretion. Afterwards, the secretomes were analysed by mass spectrometry. In this way, the CD44 protein was identified; consequently, BALF of all DPLD patients were positively tested for the presence of CD44 by ELISA. Finally, biochemical and biophysical characterizations revealed an exosomal origin of CD44. Receiver operating characteristics curve analysis confirmed CD44 in BALF as a specific and reliable biomarker of IPF and other types of DPLD accompanied with pulmonary fibrosis.

Ventilation-perfusion matching in early-stage of prone position ventilation: a prospective cohort study between COVID-19 ARDS and ARDS from other etiologies.

&#xD;Prone positioning is a therapeutic strategy for severe Acute Respiratory Distress Syndrome (ARDS). In COVID-19-associated ARDS (CARDS), the application of prone position has shown varying responses, influenced by factors such as lung recruitability and SARS-CoV-2-induced pulmonary endothelial dysfunction. This study aimed to compare the early impact of pronation on lung ventilation-perfusion matching (VQmatch) in CARDS and non-COVID-19 ARDS patients (non-CARDS).&#xD;&#xD;Approach:&#xD;This was a two-center, prospective study comparing between CARDS and non-CARDS. Electrical impedance tomography (EIT) was used to compare the VQmatch between supine and early-stage prone positions (~2h). The study identified the areas of Deadspace, shunt, and VQmatch. Within the defined VQmatch region, the global inhomogeneity index (VQmatch-GI) was computed to evaluate the degree of heterogeneity. Paired Wilcoxon signed-rank test and Chi-square test were used in statistical analysis.&#xD;&#xD;Main results:&#xD;15 CARDS patients and 14 non-CARDS patients undergoing mechanical ventilation were included. In comparison to the non-CARDS group, the CARDS group exhibited a higher prevalence of diffuse lung disease (15 [100%] vs. 4 [28.6%], CARDS vs. Non-CARDS, p＜0.001), along with elevated SOFA score, PCO2, PEEP, and Ppeak. Among non-CARDS patients, 11/14 demonstrated improved oxygenation, whereas only 5/15 CARDS patients exhibited oxygenation improvement in prone ventilation. In 13/29 patients with oxygenation improvement (defined as above 20% increase in SpO2/FiO2), there was a significant decreased deadspace (21.3 [11.5, 33.1] vs. 9.7 [7.3, 16.9], p=0.039), and VQmatch showed an upward trend. When comparing prone ventilation to supine ventilation, non-CARDS patients showed a significant improvement in overall VQmatch (Supine 65.7 [49.7, 68.5] vs. Prone 67.4 [60.8, 72.6], p=0.019). CARDS patients had a notable decrease in ventral VQmatch (VQmatch_Ventral: Supine 35.0 [26.9, 42.0] vs. Prone 22.7 [12.4, 32.9], p=0.003), and an improvement in dorsal VQmatch (VQmatch_Dorsal: Supine 33.4 [20.4, 39.4] vs. Prone 46.4 [37.4, 48.4], p=0.031), leading to no significant improvement in overall VQmatch. Ten CARDS patients with no improvement in VQmatch had increased shunting and VQmatch-GI.&#xD;&#xD;Significance:&#xD;In non-CARDS patients, the improvement in oxygenation and VQmatch following prone positioning exhibits a consistent pattern. Conversely, in CARDS patients, the impact of prone positioning reveals considerable individual variability. This study indicates that the response to short-time prone ventilation can vary in ARDS patients with different etiologies.&#xD;&#xD;Trial registration: NCT05816928, 04/17/2023, retrospectively registered.

Liver T1 mapping in Fontan patients and patients with biventricular congenital heart disease - insights into the effects of venous congestions on diffuse liver disease.

T1 relaxation time quantification on parametric maps is routinely used in cardiac imaging and may serve as a non-invasive biomarker for diffuse liver disease. In this study, we aimed to investigate the relationship between liver T1 values and cardiac function in patients with congenital heart disease (CHD) and compared patients with a biventricular circulation (BVC) to those with a Fontan circulation (FC). Magnetic resonance images from patients with CHD, obtained between June and December 2023 on a 1.5 T machine, were retrospectively reviewed. The examinations included cardiac cine sequences to assess ventricular mass and volumes, along with liver T1 mapping. T1 values were measured in eight liver segments and were compared with ventricular mass and volumes in patients with BVC and FC. In total, 104 patients (75 with BVC and 29 with FC) were included. T1 values varied significantly among the eight liver segments in both patient groups. In an age-matched comparison, patients with FC had significantly higher T1 values in all liver segments. In patients with BVC and right ventricular (RV) enlargement, a positive correlation between RV volume and T1 values in the right liver lobe was found (R > 0.504, p < 0.033). In patients with FC, the T1 values did not differ between patients with an extracardiac conduit or a lateral tunnel. Liver T1 mapping suggests more severe liver affection in patients with FC compared to those with BVC. It seems a valuable addition to cardiovascular magnetic resonance for patients who are at risk of systemic venous congestion.

Noninvasive Quantitative CT for Diffuse Liver Diseases: Steatosis, Iron Overload, and Fibrosis.

Chronic diffuse liver disease continues to increase in prevalence and represents a global health concern. Noninvasive detection and quantification of hepatic steatosis, iron overload, and fibrosis are critical, especially given the many relative disadvantages and potential risks of invasive liver biopsy. Although MRI techniques have emerged as the preferred reference standard for quantification of liver fat, iron, and fibrosis, CT can play an important role in opportunistic detection of unsuspected disease and is performed at much higher volumes. For hepatic steatosis, noncontrast CT provides a close approximation to MRI-based proton-density fat fraction (PDFF) quantification, with liver attenuation values less than or equal to 40 HU signifying at least moderate steatosis. Liver fat quantification with postcontrast CT is less precise but can generally provide categorical assessment (eg, mild vs moderate steatosis). Noncontrast CT can also trigger appropriate assessment for iron overload when increased parenchymal attenuation values are observed (eg, >75 HU). A variety of morphologic and functional CT features indicate the presence of underlying hepatic fibrosis and cirrhosis. Beyond subjective assessment, quantitative CT methods for staging fibrosis can provide comparable performance to that of elastography. Furthermore, quantitative CT assessment can be performed retrospectively, since prospective techniques are not required. Many of these CT quantitative measures are now fully automated via artificial intelligence (AI) deep learning algorithms. These retrospective and automated advantages have important implications for longitudinal clinical care and research. Ultimately, regardless of the indication for CT, opportunistic detection of steatosis, iron overload, and fibrosis can result in appropriate clinical awareness and management. ©RSNA, 2024 See the invited commentary by Yeh in this issue.

Role of impulse oscillometry in understanding the changes in physiomechanics of respiratory system in diffuse parenchymal lung diseases

Role of impulse oscillometry in understanding the changes in physiomechanics of respiratory system in diffuse parenchymal lung diseases

Pneumocystis jirovecii in the lower respiratory tract of immunocompetent individuals.

Pneumocystis jirovecii colonization rates in healthy patients are unclear. Previously published studies suggest that the fungus could play a role in the physiopathology and progression of chronic respiratory diseases. The goal of this study was to determine the prevalence of colonization by this fungus in the lower respiratory tract of immunocompetent patients who are not at risk of dysbiosis. The presence of P. jirovecii was confirmed in the bronchoalveolar lavage (BAL) samples from adults who underwent bronchoscopy for non-infectious reasons, had no immunosuppressive factors, and had not been on antibiotic treatment for at least one month. The results were compared with those obtained in the study on the presence of Pneumocystis in environmental dust samples obtained by swabbing surfaces in the participating subjects' domestic settings. Real-time PCR was the technique used for detecting the fungus in both types of samples. A total of 97 BAL samples and 49 domestic environment samples were studied. The medical reasons for needing a bronchoscopy were, mainly, the examination of both pulmonary neoplasm in 55 patients (57%) and diffuse interstitial lung disease in 21 patients (22%). The overall prevalence of P. jirovecii in our population was 7.22% in BAL samples and 0% in domestic samples. The presence of P. jirovecii in the lower respiratory tract is relevantly linked with the patient's immune status, not with an underlying pathology. Prevalence is low in immunocompetent individuals who do not have any infectious pathology and are not having antimicrobial treatments. Our results do not enable us to figure out which the environmental niche of P. jirovecii is.

Phosphorylated polysaccharides derived from Scrophulariae Radix mitigates lipopolysaccharide (LPS)-induced acute lung injury in mice by suppressing the NF-κB-mediated inflammatory response

ABSTRACT Acute lung injury (ALI) is a severe form of diffuse lung disease that poses a significant health burden in clinical settings. Numerous natural compounds derived from plants have shown effective anti-inflammatory activities with low toxicity, particularly polysaccharides, which have garnered considerable attention. This study explores key aspects of the pathogenesis of ALI and the potential mitigation effects of phosphorylated polysaccharides derived from Scrophulariae Radix (PPSR) in a lipopolysaccharide (LPS)-induced mouse model of ALI. These include alterations in the lung tissue wet/dry ratio, histopathological changes, modulation of pro-inflammatory cytokines, and inhibition of the NF-κB signalling pathway. Moreover, PPSR significantly reduced lung nitric oxide (NO) production and the expression of inducible NO synthase (iNOS) in lung tissue. The findings provide important insights into the mechanisms underlying the therapeutic effects of PPSR, emphasising its anti-inflammatory properties and its potential to alleviate the detrimental consequences of ALI.

Endostatin as a biomarker of systemic sclerosis: insights from a systematic review and meta-analysis

IntroductionThe critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating a such candidate biomarker, endostatin, an endogenous glycoprotein exerting anti-angiogenic effects, in SSc patients and healthy controls.MethodsA literature search was conducted in the electronic databases Web of Science, PubMed, and Scopus from inception to 27 May 2024. Risk of bias and certainty of evidence were assessed using the JBI checklist for analytical studies and GRADE, respectively.ResultsIn 19 eligible studies, circulating endostatin concentrations were significantly higher in SSc patients than controls (standard mean difference, SMD=0.90, 95% CI 0.56 to 1.23, p&amp;lt;0.001; low certainty of evidence). Endostatin concentrations were also significantly higher in SSc patients with digital ulcers than those without (SMD=0.43, 95% CI 0.24 to 0.62, p&amp;lt;0.001; very low certainty of evidence) and in patients with pulmonary arterial hypertension than those without (SMD=1.21, 95% CI 0.67 to 1.76, p&amp;lt;0.001; very low certainty of evidence). By contrast, no significant differences were observed between SSc patients with limited vs. diffuse disease and those with different video capillaroscopy patterns. There was limited evidence regarding endostatin concentrations in SSc patients with interstitial lung disease, telangiectasias, and gastrointestinal manifestations. There were no significant associations in meta-regression and subgroup analysis of studies investigating endostatin in SSc patients and controls between the effect size and various patient and study characteristics.DiscussionTherefore, the results of this systematic review and meta-analysis suggest that measuring endostatin can be useful in assessing the presence of SSc and specific complications, i.e., digital ulcers and pulmonary arterial hypertension, in these patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024558174.

Drug-Coated Balloons for the Treatment of Coronary Artery Disease

Drug-coated balloon (DCB) angioplasty has emerged as an alternative to drug-eluting stent (DES) implantation for percutaneous coronary intervention (PCI) in patients with coronary in-stent restenosis (ISR) as well as de novo coronary artery disease. DCBs are balloons coated with antiproliferative agents and excipients, whose aim is to foster favorable vessel healing after appropriate lesion preparation. By providing homogeneous antiproliferative drug delivery in the absence of permanent foreign body implantation, DCBs offer multiple advantages over DES, including preservation of vessel anatomy and function and positive vessel remodeling. As such, DCBs have become appealing for treatment of ISR, small-vessel disease, long lesions, simplification of bifurcation procedures, and treatment of diffuse distal disease after recanalization of chronic total occlusions. In addition, patients with high bleeding risk, diabetes, and acute coronary syndrome might also stand to benefit from DCB angioplasty. Although commercially available in numerous countries now for more than a decade, DCB only recently obtained US Food and Drug Administration approval for the treatment of coronary ISR. Moreover, preliminary results from newer generation devices tested in different clinical scenarios have raised the interest of the international community. Accordingly, an up-to-date review is timely particularly with the anticipated wave of research on the matter. Herein, this review encompasses DCB technologies, their worldwide usage, details on relevant indications, and key procedural aspects of DCB angioplasty.

COPA Syndrome-From Pathogenesis to Treatment.

Coatomer subunit α (COPA) syndrome is a mendelian autosomal dominant immune dysregulation disease characterized by early onset lung disease in the form of diffuse alveolar hemorrhaging or interstitial lung disease, frequently associated with arthritis, glomerulonephritis, and high titer autoantibodies usually mimicking other autoimmune diseases. While immunosuppressive medication has been effective in controlling arthritis, data on long-term lung disease control remains scarce, which poses a real challenge as the progression of lung disease is the main cause of poor life expectancy in COPA patients. Nevertheless, JAK inhibitor therapy seems to be the most promising therapeutic choice now.

Unsung Heroes of Coronary Interventions: Indian Cardiac Surgeons and the Challenges of South Asian Coronary Anatomy and Physiology

Background and significance: The coronary artery disease (CAD) epidemic has seen a logarithmic increase in morbidity and mortality over the past decade. Cardiovascular diseases account for about 19.1 million deaths annually—with 80% of reports coming from low and middle-income countries, which have been attributed to a lack of infrastructure, human resources, and financial coverage. In tandem with the developed world, India has also seen significant growth in interventional and surgical cardiovascular care. The dominance of coronary artery bypass grafting (CABG) procedures in India has attracted the attention of the world. With this review, the authors aim to highlight the role of cardiac surgeons in India as the “unsung heroes” of coronary interventions. Observations: A pernicious atherosclerotic pathology develops in thendian population as a result of genetic and socio-cultural predispositions, which is further complicated by anatomical and physiological differences. The pathology manifests as a diffuse disease in relatively small caliber coronary arteries, necessitating the consideration of CABG over interventional procedures. Indian cardiac surgeons have stood up to the challenge and have powered health tourism to India from around the world due to the excellent success rate and long-term outcomes at a 50–80% lesser cost than most developed countries. Beyond the costs, a major highlight is the high rate of arterial bypass and off-pump surgery. These balance the unbridled exuberance of the interventional cardiology medical–industrial complex, providing a critical balance that benefits patients and improves acute and long-term outcomes. Conclusions: Indian cardiac surgery is now known globally not only for its affordability but also for the skill set and the quality of surgeons. The surgeons’ vast experience and risk-taking capacity have made them an indispensable part of the interventional cardiology team and has allowed a multidisciplinary collaboration that inspires the world. This is evident from the rising trend of medical tourism to India.

Hospitalizations in patients with systemic sclerosis: Differences between limited and diffuse cutaneous subtypes

Aim: Systemic sclerosis is associated with significant morbidity and mortality. It remains unclear from the literature if there are differences between the subtypes of systemic sclerosis and the rate of hospitalization. Our study investigates the rates of all types of hospitalizations between limited and diffuse cutaneous systemic sclerosis. Methods: Patients have been collected prospectively using the European Scleroderma Trials and Research Group database at the Waikato Hospital, and were screened for inclusion criteria. Data were collected retrospectively on hospitalizations (total, acute, elective and infusion-related) for all patients. Results: Overall, 140 patients were included in the analysis with 84 (60.0%) with limited cutaneous systemic sclerosis, 40 (28.6%) with diffuse systemic sclerosis, 3 (2.1%) with systemic sclerosis sine scleroderma and 13 (9.3%) with overlap syndrome. The mean number of total hospitalizations in 12 months was 0.9 (SD 3.0) for patients with limited disease versus 1.7 (SD 3.0) for diffuse disease (p = 0.062). The mean number of acute hospitalizations in 12 months was 0.6 (SD 1.3) for limited and 1.2 (SD 2.4) for diffuse (p = 0.061). Patients with diffuse systemic sclerosis were more likely to be admitted for reasons relating to systemic sclerosis than patients with limited disease (p &lt; 0.001). Conclusion: Diffuse and limited systemic sclerosis subtypes appear to have similar rates of hospitalizations though there is a trend in favour of diffuse disease towards more total and acute hospitalizations. There are clear differences in causes of hospitalization between the two main subgroups.

Periodontitis in Patients Undergoing Coronary Angiography: A Cross-Sectional Study.

Background Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with coronary artery disease (CAD) being the primary contributor. Periodontitis, a common non-communicable disease, has been associated with an increased risk of CVD. Previous studies have suggested a link between the severity of periodontitis and the degree of coronary artery obstruction. Objective This study aims to investigate the correlation between the severity of periodontitis and coronary artery stenosis, as measured by the SYNTAX score I (Synergy Between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery), and to examine the association between severe periodontitis and other coronary pathologies, such as diffuse coronary disease and coronary thrombosis. Materials and methods An observational cross-sectional study was conducted at the Second Cardiology Clinic, University Multiprofile Hospital for Active Treatment "St. Marina", Varna, Bulgaria, from December 2021 to January 2024. A total of 199 patients aged 45-64 years, indicated for coronary angiography, were included. Periodontal assessment included measuring probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BoP), and plaque index (PI). Subgingival plaque samples were analyzed for periodontal pathogens. Coronary angiography was performed, and the SYNTAX score I was calculated to assess the severity of coronary artery stenosis. Statistical analyses, including chi-square tests and Spearman's correlation, were conducted to evaluate the associations. Results Among the 199 participants, 74.9% had severe periodontitis (stage III and IV). A weak but statistically significant correlation was found between mean CAL, periodontitis stage, and the SYNTAX score I (p < 0.01 and p < 0.05, respectively), indicating that more severe forms of periodontitis were associated with greater coronary artery stenosis. No correlation was observed between the presence of periodontal pathogens or the total microbial count and the SYNTAX score I. Additionally, no association was found between severe periodontitis and other coronary conditions, such as diffuse coronary disease and thrombosis. Conclusion This study provides new insights into the relationship between periodontal infection and coronary artery disease. Our findings suggest that severe periodontitis is significantly associated with a higher frequency and more complex coronary lesions, as indicated by the SYNTAX score I. However, no link was observed between specific periodontal pathogens and coronary stenosis. These results underscore the importance of early diagnosis and management of periodontal infections in patients with CAD, highlighting the potential benefits of an integrated approach to managing cardiovascular and periodontal health. Further studiesare needed to explore these associations in more depth.

Circulating MicroRNAs in Idiopathic Pulmonary Fibrosis: A Narrative Review.

Idiopathic pulmonary fibrosis (IPF) is a chronic, deathly disease with no recognized effective cure as yet. Furthermore, its diagnosis and differentiation from other diffuse interstitial diseases remain a challenge. Circulating miRNAs have been measured in IPF and have proven to be an adequate option as biomarkers for this disease. These miRNAs, released into the circulation outside the cell through exosomes and proteins, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. This review focuses on the serum/plasma miRNAs reported in IPF that have been validated by real-time PCR and the published evidence regarding the fibrotic process. First, we describe the mechanisms by which miRNAs travel through the circulation (contained in exosomes and bound to proteins), as well as the mechanism by which miRNAs perform their function within the cell. Subsequently, we summarize the evidence concerning miRNAs reported in serum/plasma, where we find contradictory functions in some miRNAs (dual functions in IPF) when comparing the findings in vitro vs. in vivo. The most relevant finding, for instance, the levels of miRNAs let-7d and miR-21 reported in the serum/plasma in IPF, correspond to those found in studies in lung fibroblasts and the murine bleomycin model, reinforcing the usefulness of these miRNAs as future biomarkers in IPF.

A clinical-radiomics nomogram based on automated segmentation of chest CT to discriminate PRISm and COPD patients

PurposeIt is vital to develop noninvasive approaches with high accuracy to discriminate the preserved ratio impaired spirometry (PRISm) group from the chronic obstructive pulmonary disease (COPD) groups. Radiomics has emerged as an image analysis technique. This study aims to develop and confirm the new radiomics-based noninvasive approach to discriminate these two groups. MethodsTotally 1066 subjects from 4 centers were included in this retrospective research, and classified into training, internal validation or external validation sets. The chest computed tomography (CT) images were segmented by the fully automated deep learning segmentation algorithm (Unet231) for radiomics feature extraction. We established the radiomics signature (Rad-score) using the least absolute shrinkage and selection operator algorithm, then conducted ten-fold cross-validation using the training set. Last, we constructed a radiomics signature by incorporating independent risk factors using the multivariate logistic regression model. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCA). ResultsThe Rad-score, including 15 radiomic features in whole-lung region, which was suitable for diffuse lung diseases, was demonstrated to be effective for discriminating between PRISm and COPD. Its diagnostic accuracy was improved through integrating Rad-score with a clinical model, and the area under the ROC (AUC) were 0.82(95 %CI 0.79–0.86), 0.77(95 %CI 0.72–0.83) and 0.841(95 %CI 0.78–0.91) for training, internal validation and external validation sets, respectively. As revealed by analysis, radiomics nomogram showed good fit and superior clinical utility. ConclusionsThe present work constructed the new radiomics-based nomogram and verified its reliability for discriminating between PRISm and COPD.

Clinical Significance of Aspergillus Sensitisation in Chronic Pulmonary Aspergillosis.

Aspergillus sensitisation (AS) is seen in many patients with chronic pulmonary aspergillosis (CPA). However, the clinical relevance of AS in CPA remains unclear. In this study, we assess the clinical significance of AS in CPA. We retrospectively analysed the data of CPA subjects, defining AS as Aspergillus fumigatus-IgE ≥ 0.35 kUA/L. We excluded subjects with asthma, allergic bronchopulmonary aspergillosis, chronic obstructive pulmonary disease (COPD) and diffuse parenchymal lung diseases (DPLD). The primary objective was to compare the demographic and clinical characteristics, lung functions (via spirometry) and treatment outcomes in CPA subjects with or without AS. The secondary objective was to explore the association between AS and airflow obstruction on spirometry using multivariable logistic regression analysis. We included 232 CPA subjects (119 females, 113 males) with a mean ± SD age of 42.1 ± 13.7 years. AS was present in 92 (39.7%) CPA patients (CPA-AS group). CPA-AS patients had higher SGRQ total scores, a higher prevalence of fungal ball, more frequent airflow obstruction and experienced more CPA relapses during follow-up compared to those without AS. Airflow obstruction was seen in 77/232 (33.2%) CPA patients. On multivariable logistic regression analysis, we found AS, increasing age and chronic fibrosing pulmonary aspergillosis independently associated with airflow obstruction on spirometry after adjusting for sex and other CPA categories. The relapse-free survival was significantly shorter in the CPA-AS group than in the CPA group. AS is common in CPA and is independently associated with airflow obstruction. More studies are required to confirm our findings.