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Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions: Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH [ABSTRACT FROM AUTHOR]

BACKGROUND: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear. METHODS: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene®) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis. RESULTS: Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with an initially lower TLC and VC developed moderate obstruction (GOLD 2). CONCLUSIONS: In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression.

Rationale: The identification of early chronic obstructive pulmonary disease (COPD) is essential to appropriately counsel patients regarding smoking cessation, provide symptomatic treatment, and eventually develop disease-modifying treatments. Disease severity in COPD is defined using race-specific spirometry equations. These may disadvantage non-White individuals in diagnosis and care. Objectives: Determine the impact of race-specific equations on African American (AA) versus non-Hispanic White individuals. Methods: Cross-sectional analyses of the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) cohort were conducted, comparing non-Hispanic White (n = 6,766) and AA (n = 3,366) participants for COPD manifestations. Measurements and Main Results: Spirometric classifications using race-specific, multiethnic, and "race-reversed" prediction equations (NHANES [National Health and Nutrition Examination Survey] and Global Lung Function Initiative "Other" and "Global") were compared, as were respiratory symptoms, 6-minute-walk distance, computed tomography imaging, respiratory exacerbations, and St. George's Respiratory Questionnaire. Application of different prediction equations to the cohort resulted in different classifications by stage, with NHANES and Global Lung Function Initiative race-specific equations being minimally different, but race-reversed equations moving AA participants to more severe stages and especially between the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 and preserved ratio impaired spirometry groups. Classification using the established NHANES racespecific equations demonstrated that for each of GOLD stages 1-4, AA participants were younger, had fewer pack-years and more current smoking, but had more exacerbations, shorter 6-minute-walk distance, greater dyspnea, and worse BODE (body mass index, airway obstruction, dyspnea, and exercise capacity) scores and St. George's Respiratory Questionnaire scores. Differences were greatest in GOLD stages 1 and 2. Race-reversed equations reclassified 774 AA participants (43%) from GOLD stage 0 to preserved ratio impaired spirometry. Conclusions: Race-specific equations underestimated disease severity among AA participants. These effects were particularly evident in early disease and may result in late detection of COPD. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis (PsO) is associated with the development of psoriatic arthritis (PsA). Patients with PsO often experience pre-PsA musculoskeletal (MSK) symptoms, leading to potential structural damage and substantial disease burden with impact on function. The objective of this study is to describe prevalence rates and evidence of MSK symptoms, including incidence of comorbid PsA diagnosis, in patients newly diagnosed with PsO and identify factors associated with PsA diagnosis. Methods: This retrospective analysis included administrative claims from the Optum Research Database for adult patients with a new PsO diagnosis between January 2008 and February 2019. Eligible patients had ≥ 2 claims for PsO on unique dates, were aged ≥ 18 years at the date of the first claim with a diagnosis of PsO (index date), and had continuous enrollment with medical and pharmacy coverage for 12 months before (baseline period) and ≥ 12 months following the index date. Primary outcomes were incidence of comorbid PsA diagnosis, prevalence of MSK symptoms other than PsA, and evidence of MSK symptoms collected at baseline and assessed in 12-month intervals through 60 months. Results: Of the 116,203 patients with newly diagnosed PsO, 110,118 were without baseline comorbid PsA. High prevalence rates of MSK symptoms among patients with only PsO were seen at baseline (47.1%), 12 months (48.2%), and 60 months (82.1%). Patient age, baseline MSK symptoms, and baseline MSK symptom–related healthcare utilization were associated with increased hazard of a PsA diagnosis. Conclusion: Increased prevalence rates of MSK symptoms and burden are experienced by patients newly diagnosed with PsO through 60 months of follow-up. Several baseline factors were associated with increased risk of PsA diagnosis. Plain Language Summary: A Study to Look at Symptoms of Muscles, Joints, and Bones in Patients with Psoriasis and Whether They Can Predict a Diagnosis of Psoriatic Arthritis Psoriasis is an inflammatory skin disease that results in areas of significant itchiness, pain, and scaling, and ultimately decreases patient quality of life. Psoriasis affects approximately 2–4% of the general US population and 1.3–2.2% of the UK population. Some patients with psoriasis may experience musculoskeletal symptoms and may go on to develop psoriatic arthritis. The goal of this study was to determine the frequency of patients with psoriasis who experienced complaints of musculoskeletal pain prior to and/or following their psoriasis diagnosis, and whether these were associated with further probability of developing psoriatic arthritis. Using a large US-based database with data from approximately 115,000 patients with newly diagnosed psoriasis, we determined the percentage of newly diagnosed psoriasis patients with existing musculoskeletal pain complaints within 12 months of their initial diagnosis. We found that 47% of newly diagnosed patients had previous musculoskeletal pain complaints, with joint pain, back pain, and overall fatigue representing the most common forms. Notably, psoriasis patients with previous joint pain were approximately 50% more likely to develop psoriatic arthritis compared with patients with no previous joint pain. Furthermore, patients with previous other forms of arthritis were nearly twice as likely to develop psoriatic arthritis. This study provides additional support that existing musculoskeletal pain in patients with newly diagnosed psoriasis may predict the potential future onset of psoriatic arthritis. These findings will help guide primary care physicians, dermatologists, and rheumatologists in understanding the importance of earlier detection of psoriatic arthritis to provide more appropriate care. [ABSTRACT FROM AUTHOR]

Background Early biologic therapy within the first 18–24 months after diagnosis is associated with improved clinical outcomes in Crohn's disease [CD]. However, the definition of the best time to initiate biologic therapy remains unclear. We aimed to assess if there is an optimal timing for early biologic therapy initiation. Methods This was a multicentre retrospective cohort study including newly diagnosed CD patients who started anti-tumour necrosis factor [TNF] therapy within 24 months from diagnosis. The timing of initiation of biologic therapy was categorised as ≤6, 7–12, 13–18, and 19–24 months. The primary outcome was CD-related complications defined as a composite of progression of Montreal disease behaviour, CD-related hospitalisations, or CD-related intestinal surgeries. Secondary outcomes included clinical, laboratory, endoscopic, and transmural remission. Results We included 141 patients where 54%, 26%, 11%, and 9% started biologic therapy at ≤6, 7–12, 13–18, and 19–24 months after diagnosis, respectively. A total of 34 patients [24%] reached the primary outcome: 8% had progression of disease behaviour, 15% were hospitalised, and 9% required surgery. There was no difference in the time to a CD-related complication according to the time of initiation of biologic therapy within the first 24 months. Clinical, endoscopic, and transmural remission was achieved in 85%, 50%, and 29%, respectively, but no differences were found according to the time of initiation of biologic therapy. Conclusion Starting anti-TNF therapy within the first 24 months after diagnosis was associated with a low rate of CD-related complications and high rates of clinical and endoscopic remission, although we found no differences with earlier initiation within this window of opportunity. [ABSTRACT FROM AUTHOR]

Abstract Introduction Psoriasis (PsO) is associated with the development of psoriatic arthritis (PsA). Patients with PsO often experience pre-PsA musculoskeletal (MSK) symptoms, leading to potential structural damage and substantial disease burden with impact on function. The objective of this study is to describe prevalence rates and evidence of MSK symptoms, including incidence of comorbid PsA diagnosis, in patients newly diagnosed with PsO and identify factors associated with PsA diagnosis. Methods This retrospective analysis included administrative claims from the Optum Research Database for adult patients with a new PsO diagnosis between January 2008 and February 2019. Eligible patients had ≥ 2 claims for PsO on unique dates, were aged ≥ 18 years at the date of the first claim with a diagnosis of PsO (index date), and had continuous enrollment with medical and pharmacy coverage for 12 months before (baseline period) and ≥ 12 months following the index date. Primary outcomes were incidence of comorbid PsA diagnosis, prevalence of MSK symptoms other than PsA, and evidence of MSK symptoms collected at baseline and assessed in 12-month intervals through 60 months. Results Of the 116,203 patients with newly diagnosed PsO, 110,118 were without baseline comorbid PsA. High prevalence rates of MSK symptoms among patients with only PsO were seen at baseline (47.1%), 12 months (48.2%), and 60 months (82.1%). Patient age, baseline MSK symptoms, and baseline MSK symptom–related healthcare utilization were associated with increased hazard of a PsA diagnosis. Conclusion Increased prevalence rates of MSK symptoms and burden are experienced by patients newly diagnosed with PsO through 60 months of follow-up. Several baseline factors were associated with increased risk of PsA diagnosis.

The need to improve health outcomes, as well as disease prognosis, has led clinicians and researchers to propose new ways of identifying COPD in its earliest forms. This initiative is based on the hypothesis that an earlier intervention would have a greater prognostic impact. However, the operational definition of a patient in the initial stages of the disease is complex, and there is still no unanimously accepted definition. GOLD has recently proposed different concepts to identify COPD in its early stages, such as COPD in young people or COPD with mild functional impairment. In addition, GOLD proposes two other concepts, called pre-COPD (symptomatic non-obstructive patients) and PRISm (preserved ratio with impaired spirometry), which aim to identify the patient at risk of developing this chronic airflow obstruction. However, despite the attractiveness of these concepts, none have been taken up universally by the medical community. A universally accepted identification of how to define COPD in its early stages is necessary as a preliminary step in order to design clinical trials to find out the best way to treat these patients. This review deals with these concepts of COPD at the onset of the disease, highlighting their importance and the problems involved in identifying them as therapeutic targets in real clinical practice. [ABSTRACT FROM AUTHOR]

Objective To summarize evidence on the relationship between early treatment (definition based on symptom/disease duration or radiographic damage) and treatment clinical response in patients with SpA. Methods A systematic literature review was conducted in studies on SpA patients treated with NSAIDs or biological/targeted synthetic DMARDs addressing the impact of symptom/disease duration or presence of radiographic damage on treatment response assessed by any disease activity outcome. For categorical outcomes, relative risk, relative risk ratio and number needed to treat were calculated, and for continuous outcomes, differences in differences, to compare groups stratified based on symptom/disease duration or the presence of radiographic damage. Results From the 8769 articles retrieved, 25 were included and 2 added by hand-search, all in axial SpA (axSpA), most of them with low risk of bias. Twenty-one studies compared groups based on symptom duration (n  = 6) or disease duration (n  = 15) and seven studies based on absence/presence of radiographic damage (two studies used two comparisons). When early axSpA was defined by symptom duration (<5 years) in randomized controlled trials, early treatment was associated with better outcomes in patients with non-radiographic axSpA [ n  = 2, ASAS40 relative risk ratio 5.24 (95% CI 1.12, 24.41) and 1.52 (0.60, 3.87)] but not in radiographic axSpA (n  = 1) [ASAS20 0.96 (0.53–1.73)]. When early axSpA was defined based on disease duration or radiographic damage, no differences were found between groups. Conclusion Evidence towards better outcomes in early axSpA is very limited and restricted to non-radiographic axSpA and <5 years symptom duration. When early axSpA is defined based on disease duration or radiographic damage, no differences in response to treatment are found. [ABSTRACT FROM AUTHOR]

Abstract Background There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements. Methods Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity. Results We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in “normal” smokers. Concavity measures were not related to either MBNW or IOS measurements. Conclusion Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction.

Abstract Background Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe. The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5–10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing, and dose of MTX in PMR remain unclear, and therefore, our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients. Methods We set up a double-blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15 mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse, prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52. Discussion No relapsing PMR patients were chosen, since the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exists. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects. Trial registration Dutch Trial Registration, NL8366 . Registered on 10 February 2020

Background: Crohn's disease (CD) and ulcerative colitis (UC) arise from a dysregulation of the balance between commensal microbiota and mucosal-associated immune system, in patients with genetic and environmental predisposition. Different pathophysiological mechanisms have been reported to influence disease history, with impact on disease phenotype and risk of complications. Objectives: This review aims to summarize the definitions of early CD and UC, analyze the underlying immunological mechanisms, and evaluate the impact of recognizing and treating early inflammatory bowel disease (IBD) on patients' prognosis (short- and long-term outcomes). Design: To address this issue, we have performed a scoping review. Data sources and methods: Three online databases (MEDLINE, Web of Science, and ScienceDirect) were searched and the results were independently screened by two reviewers. Results: From 683 records identified, 42 manuscripts evaluating early IBD in adult patients were included. The 'early CD' concept was first described in 2008. Four years later, an international consensus proposed the definition of diagnosis up to 18 months, in patients without previous or current need for disease-modifying therapies. Several other definitions have been proposed; the '2 years since diagnosis' is the most used, regardless of disease characteristics or medication. The amount of evidence on early UC is lower and more recent. Regarding early disease pathogenesis, most theories emphasize the prominent role of innate immunity, followed by early-Th1 adaptive response. Conclusion: The treatment of early CD seems to be crucial for the management of CD patients, impacting short-, medium-, and long-term outcomes. On the other hand, the early treatment of UC appears to be less advantageous, yet evidence comes from only a few retrospective studies. [ABSTRACT FROM AUTHOR]

The need to improve health outcomes, as well as disease prognosis, has led clinicians and researchers to propose new ways of identifying COPD in its earliest forms. This initiative is based on the hypothesis that an earlier intervention would have a greater prognostic impact. However, the operational definition of a patient in the initial stages of the disease is complex, and there is still no unanimously accepted definition. GOLD has recently proposed different concepts to identify COPD in its early stages, such as COPD in young people or COPD with mild functional impairment. In addition, GOLD proposes two other concepts, called pre-COPD (symptomatic non-obstructive patients) and PRISm (preserved ratio with impaired spirometry), which aim to identify the patient at risk of developing this chronic airflow obstruction. However, despite the attractiveness of these concepts, none have been taken up universally by the medical community. A universally accepted identification of how to define COPD in its early stages is necessary as a preliminary step in order to design clinical trials to find out the best way to treat these patients. This review deals with these concepts of COPD at the onset of the disease, highlighting their importance and the problems involved in identifying them as therapeutic targets in real clinical practice.

Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with offtarget tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKTmTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for lessdeveloped agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised. [ABSTRACT FROM AUTHOR]

Background: C-reactive protein (CRP) is an acute phase reactant influenced by inflammation and tissue damage. Elevated CRP levels have been associated with poor outcome of various cancers including breast cancer. However, evidence regarding a potential impact of CRP levels on outcome of neoadjuvant chemotherapy (NACT) in patients with early breast cancer (EBC) is insufficient. Methods: Patients who had received NACT for EBC and had available data regarding CRP levels before therapy, pathologic complete remission (pCR), and follow-up were included. The association between CRP at baseline and outcome parameters was analyzed. Results: 152 women were included in this analysis; median follow-up was 5.8 years. No association between CRP at baseline and pCR rates could be detected. 6.6% of the patients developed a local recurrence, 10.5% developed a distant recurrence, and 5.2% died from breast cancer. A negative correlation (Spearman-Rho) between CRP at baseline and overall survival (OS) (correlation coefficient (CC) −0.255; p = 0.45), disease-free survival (DFS) (CC −0.348; p = 0.075), local recurrence-free survival (LRFS) (CC −0.245; p = 0.327), and distant DFS (DDFS) (CC −0.422; p = 0.057) was not statistically significant, although especially in DFS and DDFS a strong trend was detected. The probability of death from breast cancer was 2% if the CRP was <0.08 mg/dL and 40% if the CRP was >2.08 mg/dL; this association was highly statistically significant (χ2; p < 0.001). These results were independent from age, estrogen and progesterone receptor status, HER2 status, nodal status, and grading. The hazard ratio for OS was 5.75 (p = 0.004) for CRP <0.08 mg/dL versus CRP >2.08 mg/dL. Discussion/Conclusion: CRP at baseline is not predictive for pCR in EBC after NACT in our patient dataset. However, an association of parameters of long-term prognosis with CRP could be demonstrated. Although the correlations of higher CRP levels at baseline and shorter OS, DFS, LRFS, and DDFS were not significant, a strong trend could be detected that was reproduced in the analysis of different groups of CRP levels and the probability of breast cancer mortality. Higher CRP levels are indicating a worse prognosis in EBC after NACT in this retrospective analysis. These results justify further investigation of CRP not as a predictive parameter for pCR but as a biomarker of long-term prognosis in EBC in prospective trials and may lead to therapeutic approaches with the aim of lowering CRP levels. [ABSTRACT FROM AUTHOR]

Background/aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH., Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients., Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH., Conclusions: Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

Background: There is increasing evidence of small airway abnormalities in smokers despite normal spirometry. The concavity in the descending limb of the maximum expiratory flow curve (MEFV) is a recognised feature of obstruction and can provide information beyond FEV1, and potentially early smoking-related damage. We aimed to evaluate concavity measures compared to known small airway measurements.Methods: Eighty smokers with normal spirometry had small airway function assessed: multiple breath nitrogen washout (MBNW) from which ventilation heterogeneity in the diffusion-dependent acinar (Sacin) and convection-dependent conductive (Scond) airways were assessed, and impulse oscillometry system (IOS) from which respiratory resistance and reactance at 5 Hz (R5 and X5) were measured. Concavity measures were calculated from the MEFV, partitioned into global and peripheral concavity.Results: We found abnormal peripheral and global concavity as well as acinar ventilation heterogeneity are common in "normal" smokers. Concavity measures were not related to either MBNW or IOS measurements.Conclusion: Abnormalities in concavity indices and MBNW or oscillometry parameters are common in smokers despite normal spirometry. However, these measures likely reflect different mechanisms of peripheral airway dysfunction. [ABSTRACT FROM AUTHOR]

Background: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease affecting people older than 50, resulting in pain and stiffness of the neck, shoulder, and pelvic girdle. To date, glucocorticoids (GC) remain the cornerstone of treatment, but these have several drawbacks. Firstly, a large proportion of patients do not achieve GC-free remission within either the first (over 70%) or second year of treatment (over 50%). Secondly, GC-related adverse events (AE) occur in up to 65% of patients and can be severe. The current EULAR/ACR guidelines for PMR recommend early introduction of methotrexate (MTX) as a GC sparing agent in patients at risk for worse prognosis. However, earlier trials of low to medium quality only studied MTX dosages of 7.5-10 mg/week with no to modest effect. These doses may be suboptimal as MTX is recommended in higher doses (25 mg/week) for other inflammatory rheumatic diseases. The exact role, timing, and dose of MTX in PMR remain unclear, and therefore, our objective is to study the efficacy of MTX 25 mg/week in recently diagnosed PMR patients.Methods: We set up a double-blind, randomized, placebo-controlled superiority trial (PMR MODE) to assess the efficacy of MTX 25 mg/week versus placebo in a 1:1 ratio in 100 recently diagnosed PMR patients according to the 2012 EULAR/ACR criteria. All patients will receive prednisolone 15 mg/day, tapered to 0 mg over the course of 24 weeks. In case of primary non-response or disease relapse, prednisolone dose will be temporarily increased. Assessments will take place at baseline, 4, 12, 24, 32, and 52 weeks. The primary outcome is the difference in proportion of patients in GC-free remission at week 52.Discussion: No relapsing PMR patients were chosen, since the possible benefits of MTX may not outweigh the risks at low doses and effect modification may occur. Accelerated tapering was chosen in order to more easily identify a GC-sparing effect if one exists. A composite endpoint of GC-free remission was chosen as a clinically relevant endpoint for both patients and rheumatologist and may reduce second order (treatment) effects.Trial Registration: Dutch Trial Registration, NL8366 . Registered on 10 February 2020. [ABSTRACT FROM AUTHOR]

Abstract Background The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood. Methods This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance. Results Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p

The development of Crohn's disease (CD) is characterized by a breakdown of homeostatic immune-bacterial communication, which takes place at the intestinal mucosa when environmental triggers impact genetically predisposed individuals. Converging lines of evidence support the hypothesis that this pathogenetic model develops through sequential, although inter-related, steps that indicate failure of mucosal defense mechanisms at various stages. In this context, immunologic phenomena that mediate the initial appearance of inflammatory lesions across the intestinal tissue may differ substantially from those that mediate and perpetuate chronic inflammatory responses. A compromise in the integrity of the epithelial barrier is among the earliest events and leads to accelerated influx of intraluminal antigens and intact microorganisms within the immunologically rich lamina propria. Inadequate clearance of invading microorganisms also may occur as a result of defects in innate immunity, preventing the timely and complete resolution of acute inflammatory responses. The final step is the development of persistent adaptive responses, which also differ between early and late Crohn's disease. Current progress in our ability to delineate single-cell transcriptomics and proteomics has allowed the discovery of cellular and molecular mechanisms that participate in each sequential step of CD development. This not only will advance our understanding of CD pathogenesis, but also facilitate the design of targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

Abstract Introduction Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. Methods C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA,

Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%).

Rationale: Individuals who will develop chronic obstructive pulmonary disease (COPD) could be identified at an early age before clinical manifestations appear. Objectives: We investigated risk of clinical COPD 10 years later in young adults from the general population with and without early COPD with a focus on smoking exposure. Methods: We included 14,870 individuals aged 20-100 years from the Copenhagen General Population Study with spirometry 10 years apart. Early COPD was defined as baseline FEV1/FVC less than the lower limit of normal in individuals aged <50 years. Outcomes included clinical COPD at final examination 10 years later (chronic respiratory symptoms with FEV1/FVC <0.70 and FEV1 <80% predicted) and acute exacerbation hospitalizations during follow-up. Measurements and Main Results: Among 5,497 individuals aged <50 years at baseline with FEV1/FVC ≥0.70, 104 (3%) developed clinical COPD 10 years later; 4% of smokers with ≥10 pack-years had early COPD; 3% of smokers with <10 pack-years had early COPD; and 2% of never-smokers had early COPD. Among smokers with ≥10 pack-years, 24% developed clinical COPD in those with early COPD versus 4% in those without early COPD. Corresponding numbers were 10% and 1% in smokers with <10 pack-years and 3% and <1% in never-smokers, respectively. Among individuals with early COPD, odds ratios for clinical COPD 10 years later were 7.77 (95% confidence interval [CI], 4.10-14.7) in smokers with ≥10 pack-years and 8.56 (95% CI, 4.92-14.9) in all smokers, whereas hazard ratios for acute exacerbation hospitalizations were 4.16 (95% CI, 1.66-10.5) and 4.33 (95% CI, 1.89-9.93), respectively. Results were validated in the Copenhagen City Heart Study. Conclusions: Depending on amount of smoking exposure, <24% of young adults in the general population with early COPD develop clinical COPD 10 years later. A smoking exposure threshold for early COPD should be reconsidered, as younger individuals are less represented in those with high smoking exposure. [ABSTRACT FROM AUTHOR]

Introduction: Insulin and the insulin-like growth factor (IGF) family play a key role in breast cancer (BC). Objective: In this study, we evaluated on a genomic scale the potential prognostic value of insulin signaling in early BC. Methods: Candidate genes were selected from the published literature and gene expression profiling experiments. Three publicly available BC datasets, containing gene expression data on 502 cases, were used to test the prognostic ability of the score. The gene signature was developed on GSE1456, containing microarray data from 159 patients, split into a training set (102 breast tumors) and a validation set (n = 57). GSE3494 and GSE2990 (350 patients) were used for external validation. Univariate Mann-Whitney test was used to identify genes differentially expressed between relapsed and nonrelapsed patients. Expression of genes significantly correlated with relapse was combined in a linear score. Patients were classified as low or high risk with respect to the median value. Results: On the training set, 15 genes turned out to be differentially expressed: 8-year disease-free survival (DFS) was 51 and 91% in the high- and low-risk group (p < 0.001), respectively. In the validation set, DFS was 97 and 54% (p = 0.009), respectively. External validation: 8-year DFS was 72 and 61%, respectively, in GSE3494 (p = 0.03) and 74 and 55% in GSE2990 (p = 0.03). By multivariate analyses, the insulin signature was significantly associated with DFS, independently of age, hormone receptor status, nodal status, and grade. Conclusions: Our findings indicate that the insulin pathway is involved in BC prognosis at a genomic level and provide a window of selectivity for preventive and treatment strategies targeting the insulin/IGF pathway in BC patients. [ABSTRACT FROM AUTHOR]

Objectives Our aim is to understand clinical characteristics, real-life treatment strategies, outcomes of early PsA patients and determine the differences between the inception and established PsA cohorts. Methods PsArt-ID (Psoriatic Arthritis- International Database) is a multicentre registry. From that registry, patients with a diagnosis of PsA up to 6 months were classified as the inception cohort (n ==388). Two periods were identified for the established cohort: Patients with PsA diagnosis within 5–10 years (n  = 328), ≥10 years (n  = 326). Demographic, clinical characteristics, treatment strategies, outcomes were determined for the inception cohort and compared with the established cohorts. Results The mean (s. d.) age of the inception cohort was 44.7 (13.3) and 167/388 (43.0%) of the patients were male. Polyarticular and mono-oligoarticular presentations were comparable in the inception and established cohorts. Axial involvement rate was higher in the cohort of patients with PsA ≥10 years compared with the inception cohort (34.8% vs 27.7%). As well as dactylitis and nail involvement (P = 0.004, P = 0.001 respectively). Both enthesitis, deformity rates were lower in the inception cohort. Overall, 13% of patients in the inception group had a deformity. MTX was the most commonly prescribed treatment for all cohorts with 10.7% of the early PsA patients were given anti-TNF agents after 16 months. Conclusion The real-life experience in PsA patients showed no significant differences in the disease pattern rates except for the axial involvement. The dactylitis, nail involvement rates had increased significantly after 10 years from the diagnosis and the enthesitis, deformity had an increasing trend over time. [ABSTRACT FROM AUTHOR]

Background: The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood.Methods: This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance.Results: Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p < 0.003). Proportions of employed patients were 50.6%, 50.9% and 27.5% in Groups 1, 2 and 3, respectively. For patients in part-time employment, the number of hours worked was significantly higher in Group 2 patients versus Group 3 (p = 0.002). Group 2 also had significantly lower levels of work absenteeism and overall work impairment compared with Group 1 (p < 0.001). Patients in Group 3 reported worse health utility scores (p ≤ 0.002), moderate or worse problems in the EQ-5D-5L self-care and usual activity domains (p ≤ 0.001), and lower HRQoL as assessed by FACT summary scores (p < 0.001 for FACT-B and -G) than Groups 1 and 2. Poorer HRQoL was significantly associated with higher work impairment (p < 0.001), with the strongest relationships being observed between activity impairment and HRQoL (Pearson's r: 0.67).Conclusions: Metastatic disease and treatment of HER2-positive BC adversely impacted on work productivity and HRQoL. The results of this study support the idea that being able to delay or prevent the metastatic recurrence of BC, for example by extending the time patients are in remission or at early stage of BC, has wider benefits in terms of patient productivity and HRQoL. [ABSTRACT FROM AUTHOR]

Articulating a satisfactory definition of a disease is surprisingly difficult. Despite the alarming individual, societal and economic burden of chronic obstructive pulmonary disease (COPD), diagnosis is still largely based on a physiologically dominated disease conception, with spirometrically determined airflow limitation as a cardinal feature of the disease. The diagnostic inaccuracy and insensitivity of this physiological disease definition is reviewed considering scientific developments of imaging of the respiratory system in particular. Disease must be approached as a fluid concept in response to new scientific and medical discoveries, but labelling as well as mislabelling someone as diseased, will have enormous individual, social and financial implications. Nosology of COPD urgently needs to dynamically integrate more sensitive diagnostic procedures to detect the breadth of abnormalities early in the disease process. Integration of broader information for the identification of abnormalities in the respiratory system is a cornerstone for research models of underlying pathomechanisms to create a breakthrough in research.

Introduction: Achievement of remission is a key treatment goal for patients with axial spondyloarthritis (axSpA). C-OPTIMISE assessed achievement of sustained clinical remission in patients with axSpA, including radiographic (r) and non-radiographic (nr) axSpA, during certolizumab pegol (CZP) treatment, and subsequent maintenance of remission following CZP dose continuation, dose reduction or withdrawal. Here, we report outcomes from the first 48 weeks (induction period) of C-OPTIMISE, during which patients received open-label CZP. Methods: C-OPTIMISE (NCT02505542) was a two-part, multicenter, phase 3b study in adult patients with early axSpA (r-/nr-axSpA), including a 48-week open-label induction period followed by a 48-week maintenance period. Patients with active adult-onset axSpA, < 5 years' symptom duration, and fulfilling Assessment of SpondyloArthritis international Society classification criteria, were included. During the induction period, patients received a loading dose of CZP 400 mg at weeks 0, 2, and 4, followed by CZP 200 mg every 2 weeks (Q2W) up to week 48. The main outcome of the 48-week induction period was the achievement of sustained clinical remission (defined as an Ankylosing Spondylitis Disease Activity Score [ASDAS] < 1.3 at week 32 and < 2.1 at week 36 [or vice versa], and < 1.3 at week 48). Results: In total, 736 patients (407 with r-axSpA, 329 with nr-axSpA) were enrolled into the study. At week 48, 43.9% (323/736) of patients achieved sustained remission, including 42.8% (174/407) of patients with r-axSpA and 45.3% (149/329) with nr-axSpA. Patients also demonstrated substantial improvements in axSpA symptoms, MRI outcomes and quality of life measures. Adverse events occurred in 67.9% (500/736) of patients, of which 6.0% (44/736) were serious. Conclusions: Over 40% of patients with early axSpA achieved sustained remission during 48 weeks of open-label CZP treatment. Additionally, patients across the axSpA spectrum demonstrated substantial improvements in imaging outcomes and quality of life following treatment. No new safety signals were identified. Trial Registration: NCT02505542. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to evaluate the use of ultrasonography (USG) including power Doppler in detecting hand and wrist joint changes in early rheumatoid arthritis (RA) and to compare USG findings with magnetic resonance imaging (MRI). Materials and Methods: Thirty-four patients diagnosed as RA by 2010 ACR/EULAR criteria; with the onset of symptoms within last one year, were included in the study after institute ethical clearance and informed consent to undergo USG and contrast-enhanced MRI of the dominant affected hand. Second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints and wrist joints (total nine joints) were evaluated for synovitis, erosions along with tenosynovitis. USG and MRI features were compared; agreement on the two imaging modalities as well as sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of ultrasonography compared to MRI (gold standard) was calculated. Results: One hundred thirty-six MCP, 136 PIP and 34 wrist joints (total 306 joints) and 136 flexor tendons were evaluated. The sensitivity, specificity, PPV, NPV and diagnostic accuracy of USG for diagnosing synovitis was 78.6%, 91.1%, 86.1%, 85.8%, 86.3%; for erosions 67.2%, 97.5%, 84.8%, 90.5%, 91.5%; for tenosynovitis 86.5%, 100%, 100%, 92.3% and 94.8% respectively. The overall agreement between USG and MRI for detection of synovitis was achieved in 83% joints and for erosions in 89.5% joints. Conclusion: In early RA, USG was nearly as effective in diagnosing features of joint and tendon sheath involvement, with relatively better performance of USG for tenosynovitis. The performance of USG in diagnosing erosions was limited likely due to difficult access of three-dimensional joint structure. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate early changes in retinal layers using optical coherence tomography (OCT) in patients with long‐standing type 1 diabetes (DM1) receiving intensified insulin therapy. Methods: In a cross‐sectional case–control study 150 patients with DM1 and 150 age‐ and sex‐matched healthy control participants underwent OCT imaging. Scans of both eyes were analysed for different layers (NFL, GCL (+IPL), INL, outer layer complex (OLC, including OPL, ONL and ELM) and photoreceptors (PR)) in all subfields of an ETDRS grid. All analyses were performed semi‐automatically using custom software by certified graders of the Vienna Reading Center. ANOVA models were used to compare the mean thickness of the layers between patients and controls. Results: Six hundred eyes with 512 datapoints in 49 b‐scans in each OCT were analysed. Mean thickness in patients/controls was 31.35 μm/30.65 μm (NFL, p = 0.0347), 76.7 μm/73.15 μm (GCL, p ≤ 0.0001), 36.29 μm/37.13 μm (INL, p = 0.0116), 114.34 μm/112.02 μm (OLC, p < 0.0001) and 44.71 μm/44.69 μm (PR, p = 0.9401). When evaluating the ETDRS subfields separately for clinically meaningful hypotheses, a significant swelling of the GCL in patients could be found uniformly and a central swelling for the OLC, whereas the distribution of NFL and INL thickening suggests that their statistical significance was not clinically relevant. Conclusion: These preliminary results demonstrate that preclinical retinal changes in patients with long‐standing DM1 can be found by retinal layer evaluation. However, the changes are layer‐specific, with significant thickening of the GCL and less so of the OLC suggesting a role as an early sign for diffuse swelling and the evolution of DME even in well‐controlled diabetes. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (ICC) is a rare disease with poor outcome, despite advances in surgical and non-surgical treatment. Recently, studies have reported a favorable long-term outcome of “very early” ICC (based on tumor size and absence of extrahepatic disease) after hepatic resection and liver transplantation, respectively. However, the prognostic value of tumor size and a reliable definition of early disease remain a matter of debate. Patients undergoing resection of histologically confirmed ICC between February 1996 and January 2021 at our institution were reviewed for postoperative morbidity, mortality, and long-term outcome after being retrospectively assigned to two groups: “very early” (single tumor ≤ 3 cm) and “advanced” ICC (size > 3 cm, multifocality or extrahepatic disease). A total of 297 patients were included, with a median follow-up of 22.8 (0.1–301.7) months. Twenty-one (7.1%) patients underwent resection of “very early” ICC. Despite the small tumor size, major hepatectomies (defined as resection of ≥3 segments) were performed in 14 (66.7%) cases. Histopathological analyses revealed lymph node metastases in 5 (23.8%) patients. Patients displayed excellent postoperative outcome compared to patients with “advanced” disease: intrahospital mortality was not observed, and patients displayed superior long-term survival, with a 5-year survival rate of 58.2% (versus 24.3%) and a median postoperative survival of 62.1 months (versus 25.3 months; p = 0.013). In conclusion, although the concept of a “very early” ICC based solely on tumor size is vague as it does not necessarily reflect an aggressive tumor biology, our proposed definition could serve as a basis for further studies evaluating the efficiency of either surgical resection or liver transplantation for this malignant disease.

James A Stockley,1 Brendan G Cooper,1 Robert A Stockley,2 Elizabeth Sapey3 1Department of Lung Function and Sleep, 2Department of Respiratory Medicine, University Hospital Birmingham, 3Institute of Inflammation and Ageing, Centre for Translational Inflammation Research, University of Birmingham, Edgbaston, Birmingham, UK Abstract: It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability to design efficacious therapies. This is particularly true for COPD, where most patients are diagnosed with moderate-to-severe airflow obstruction and little is known about the inflammatory processes present in early disease. There is great interest in developing screening tests that can identify those most at risk of developing COPD before airflow obstruction has developed for the purpose of research and clinical care. Landmark pathology studies have suggested that damage to the small airways precedes the development of airflow obstruction and emphysema and, thus, presents an opportunity to identify those at risk of COPD. However, despite a number of physiological tests being available to assess small airways function, none have been adopted into routine care in COPD. The reasons that tests of small airways have not been utilized widely include variability in test results and a lack of validated reference ranges from which to compare results for some methodologies. Furthermore, population studies have not consistently demonstrated their ability to diagnose disease. However, the landscape may be changing. As the equipment that delivers tests of small airways become more widely available, reference ranges are emerging and newer methodologies specifically seek to address variability and difficulty in test performance. Moreover, there is evidence that while tests of small airways may not be helpful across the full range of established disease severity, there may be specific groups (particularly those with early disease) where they might be informative. In this review, commonly utilized tests of small airways are critically appraised to highlight why these tests may be important, how they can be used and what knowledge gaps remain for their use in COPD. Keywords: small airways, COPD, early disease, physiology, emphysema, airflow obstruction

Background: Abnormal lung volumes representing air trapping identify the subset of smokers with preserved spirometry who develop spirometric chronic obstructive pulmonary disease (COPD) and adverse outcomes. However, how lung volumes evolve in early COPD as airflow obstruction develops remains unclear., Methods: To establish how lung volumes change with the development of spirometric COPD, we examined lung volumes from the pulmonary function data (seated posture) available in the U.S. Department of Veterans Affairs electronic health records (n=71,356) and lung volumes measured by computed tomography (supine posture) available from the COPD Genetic Epidemiology (COPDGene ® ) study (n=7969) and the SubPopulations and InterMediate Outcome Measures In COPD Study (SPIROMICS) (n=2552) cohorts, and studied their cross-sectional distributions and longitudinal changes across the airflow obstruction spectrum. Patients with preserved ratio-impaired spirometry (PRISm) were excluded from this analysis., Results: Lung volumes from all 3 cohorts showed similar patterns of distributions and longitudinal changes with worsening airflow obstruction. The distributions for total lung capacity (TLC), vital capacity (VC), and inspiratory capacity (IC) and their patterns of change were nonlinear and included different phases. When stratified by airflow obstruction using Global initiative for chronic Obstructive Lung Disease (GOLD) stages, patients with GOLD 1 (mild) COPD had larger lung volumes (TLC, VC, IC) compared to patients with GOLD 0 (smokers with preserved spirometry) or GOLD 2 (moderate) disease. In longitudinal follow-up of baseline GOLD 0 patients who progressed to spirometric COPD, those with an initially higher TLC and VC developed mild obstruction (GOLD 1) while those with an initially lower TLC and VC developed moderate obstruction (GOLD 2)., Conclusions: In COPD, TLC, and VC have biphasic distributions, change in nonlinear fashions as obstruction worsens, and could differentiate those GOLD 0 patients at risk for more rapid spirometric disease progression., (JCOPDF © 2023.)

Abstract: Background: Axial spondyloarthritis (axSpA) is a common inflammatory arthritis of the sacroiliac joints and the spine. The best‐known and most studied form of axSpA is ankylosing spondylitis. Design: In this review, we provide a brief overview of the pathophysiology of axSpA. In addition, we performed a quantitative text analysis of reviews on the pathogenesis of axSpA published in the last 10 years to establish the current consensus in various fields of research into the pathogenesis of axSpA. Results: There appears to be broad consensus on genetic risk factors and the involvement of the immune system in the initiation phase of the disease although little consensus was found on which specific immune cells drive disease. Moreover, despite relatively little data available, alterations in the microbiome are commonly thought to be involved in disease. Abnormal bone formation is the most prominent pathogenic factor thought to be involved in disease progression. Conclusion: So, although the pathophysiology of axSpA remains incompletely understood, the progress in recent years in several fields of research in axSpA including genetics, diagnosis, imaging and therapeutics, hold great promise for the future. [ABSTRACT FROM AUTHOR]