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Objective: The main aim of the study was to evaluate the performance of 2 proposed criteria for difficult-to-treat (D2T) psoriatic arthritis (PsA) in a group of patients and to evaluate the agreement between the 2 sets of criteria., Methods: We performed a cross-sectional analysis of 2 longitudinal cohorts of patients with PsA fulfilling the Classification Criteria for Psoriatic Arthritis (CASPAR), with at least 1 year of follow-up. A detailed medical history was collected and a physical examination was performed for all recruited patients. The proposed criteria for patients with D2T PsA were applied in our group. To test the performance of the 2 sets of criteria, we used an external validator (absence of patient acceptable symptom state + physician global assessment ≥ 6 cm). Finally, the agreement between the 2 sets of criteria was assessed., Results: We evaluated 378 patients with PsA (219 male/159 female), with a mean age (range) of 58 (19-75) years. Seventy-five (19.8%) patients fulfilled the D2T criteria proposed by Perrotta et al and 58 (15.3%) the D2T criteria proposed by Kumthekar et al. Both criteria showed comparable performance, with low sensitivity (Perrotta: 37.8%, Kumthekar: 29.7%) but good specificity (Perrotta: 82.1%, Kumthekar: 86.2%). Finally, the agreement between the 2 sets of criteria is substantial (Fleiss [Formula: see text] 0.72), suggesting that both criteria identify nearly the same group of patients., Conclusion: Our study compared 2 published sets of criteria showing comparable performance and substantial agreement. This study may pave the way for further research in this field., (Copyright © 2024 by the Journal of Rheumatology.)

Introduction: The Patient Acceptable Symptoms State (PASS) is a validated instrument that is used to assess whether a patient with psoriatic arthritis (PsA) accepts her/his disease status by asking them a simple question: "Think about all the ways your PsA has affected you during the last 48 h. If you were to remain in the next few months as you were during the last 48 h, would this be acceptable to you?" The aim of the present study was to explore any PASS differences in patients with PsA based on sex by looking at the corresponding thresholds of Disease Activity for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Impact of the Disease-12 (PsAID-12) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) in female and male patients., Methods: This was a cross-sectional study that included two PsA cohorts. To identify the DAPSA, PsAID and HAQ-DI thresholds that differentiated patients who reported "yes" in response to the PASS question from those who reported "no," we used the receiver operating characteristic curves both for the female and male sexes. Moreover, Cohen's kappa test was used to determine the agreement of a PASS "yes" with DAPSA ≤ 14, PsAID ≤ 4 and HAQ-DI ≤ 0.5., Results: Three-hundred ten patients were considered for the study. The DAPSA, PsAID-12 and HAQ-DI thresholds that differentiated PASS "yes" patients from PASS "no" patients were 11.7, 1.85 and 0.625 in male patients and 13.3, 3.85 and 0.750 in female patients, respectively. A PASS "yes" and DAPSA ≤ 14 showed moderate agreement in males (kappa = 0.56) and good agreement in females (kappa = 0.80); the agreement between a PASS "yes" and PsAID ≤ 4 and between a PASS "yes" and HAQ-DI ≤ 0.5 was higher in female patients (moderate)., Conclusion: Female patients accept their disease at higher DAPSA, PsAID and HAQ-DI values than male patients do. The clinical meaning of this could be that a female patient generally has a greater global disease acceptance inclination. Therefore, this study further supports the concept that sex differences are present in patients with PsA., (© 2024. The Author(s).)

Purposeof Review: Male fertility is an emergent issue that should be considered in clinical practice, when dealing with chronic inflammatory diseases in young men. As it is known, the chronic inflammation is the main pathophysiologic mechanism in some rheumatological conditions such as spondyloarthritis (SpA), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Therefore, it is paramount to be aware if these diseases could impair male fertility, both due to the inflammation or to the treatments needed: we reviewed the literature on the most relevant and recent evidence on male fertility in patients affected by SpA, AS and PsA., Recent Findings: Rheumatological inflammatory diseases (included SpA, AS and PsA) could impair the family planning in man life, especially when diagnosed at young age. Moreover, focusing on sperm quality, it seems that a link between sperm quality impairment and a higher disease activity exist. Focusing on therapies, Tumor Necrosis Factor inhibitors showed a safety profile on human male fertility in clinical studies. Recently, a prospective study and two double-blind placebo-controlled trials assessed the impact of methotrexate and Filgotinib on semen parameters, respectively, showing a safety profile of these drugs on human semen quality. However, there are no clinical data on the impact of Interleukin (IL)17 inhibitors(i), IL12-23i and IL23i. Concerning male fertility in SpA, AS and PsA, an unmet clinical need is still present and new studies are needed to understand the association between these diseases and male fertility, and the implication of the therapies used for these diseases. This narrative review provides an overview of the available data on male fertility in patients affected by SpA, AS and PsA., (© 2024. The Author(s).)

Background: The recent advances in precision oncology for lung cancer treatment has focused attention on the importance of obtaining appropriate specimens for tissue diagnosis as well as comprehensive molecular profiling. CT scan-guided biopsies and bronchoscopy are currently the main procedures employed for tissue sampling. However, growing evidence suggests that ultrasound-guided biopsies may represent an effective as well as safe approach in this diagnostic area. This study explores the safety and the diagnostic yield for cancer molecular profiling in ultrasound-guided percutaneous lung lesion biopsies (US-PLLB)., Methods: One hundred consecutive patients with suspected lung cancer, between January 2021 and May 2024, who had ultrasound-guided lung biopsies have been retrospectively analyzed. Molecular profiling was conducted with next-generation sequencing Genexus using Oncomine precision assay or polymerase chain reaction according to specimen quality. Qualitative immunohistochemical assay of programmed death ligand 1 (PD-L1) expression was evaluated by the Dako PD-L1 immunohistochemistry 22C3 pharmDx assay. The co-primary endpoints were the molecular diagnostic yield and the safety profile of US-guided lung biopsies., Results: From January 2021 to May 2024, 100 US-guided lung biopsies were carried out and 95 were considered for inclusion in the study. US-PLLB provided informative tissue for a histological evaluation in 93 of 95 patients with an overall diagnostic accuracy of 96.84% [Sensitivity: 92.63%; Specificity: 96.84%; PPV: 100%; NPV: 100%]. Sixty-Six patients were diagnosed with NSCLC (69.47%) and were considered for molecular diagnostic yield evaluation and PD-L1 testing. Four patients had malignant lymphoid lesions. US-PLLB was not adequate to achieve a final diagnosis in three patients (3.16%). Complete molecular profiling and PD-L1 evaluation were achieved in all patients with adenocarcinoma (molecular diagnostic yield: 100%). PD-L1 evaluation was achieved in 28 of 29 patients (96.55%) with either SCC or NOS lung cancer. The overall complication rate was 9.47% (n = 9). Six patients (6.31%) developed pneumothorax, while three patients (3.16%) suffered mild haemoptysis without desaturation., Conclusions: According to our findings, US-guided lung biopsy is a safe, minimally invasive procedure in patients with suspected lung malignancies, providing an excellent diagnostic yield for both comprehensive molecular profiling and PD-L1 testing. In addition, our results suggest that US-guided biopsy may also be an effective diagnostic approach in patients with suspected lung lymphoma.

Idiopathic pulmonary fibrosis (IPF) has traditionally been considered the archetype of progressive fibrotic interstitial lung diseases (f-ILDs), but several other f-ILDs can also manifest a progressive phenotype. Integrating genomic signatures into clinical practice for f-ILD patients may help to identify patients predisposed to a progressive phenotype. In addition to the risk of progressive pulmonary fibrosis, there is a growing body of literature examining how pharmacogenomics influences treatment response, particularly regarding the efficacy and safety profiles of antifibrotic and immunomodulatory agents. In this narrative review, we discuss current studies in IPF and other forms of pulmonary fibrosis, including systemic autoimmune disorders associated ILDs, sarcoidosis and hypersensitivity pneumonitis. We also provide insights into the future direction of research in this complex field.

Introduction: The concept of severity in a multidomain disease such as psoriatic arthritis (PsA) is still not well defined. The aim of this study was to identify the clinical characteristics of patients with severe peripheral PsA., Methods: Retrospective analysis of a longitudinal cohort. Demographic and clinical characteristics of patients with PsA were collected at baseline and at last follow-up. We defined the severe population using the modified Composite Psoriatic Disease Activity Index (mCPDAI); which excludes ankylosing spondylitis quality of life scale). Hence, patients with a score of 3 in at least one domain were defined as having severe PsA. Clinical characteristics of patients fulfilling the definition of severe PsA were compared to those non-severe., Results: We evaluated 177 patients with peripheral PsA (M/F: 98/76). Of these, 64 (36.1%) were identified as severe according to the mCPDAI criteria, at baseline. Eighteen patients (10.1%) at last follow-up still met the definition of severe PsA. At last follow-up visit, severe patients with PsA were only males (18/18, P < 0.01) and have worse outcomes in terms of disease activity, pain, function, and impact of disease. Male sex and the severity of skin involvement at baseline were factors associated with the presence of severe PsA. The agreement between the presence of severe PsA and the absence of minimal disease activity was slight [Cohen's k: 0.174 (0.084-0.264)]., Conclusions: Our study showed that severe patients with PsA had more disease activity, pain, and impact of disease than non-severe patients. Furthermore, we demonstrated that severity and disease activity are not interchangeable concepts., (© 2024. The Author(s).)

Introduction: An overarching principle for the management of psoriatic arthritis (PsA) is a shared decision-making process between physicians and patients. The aim of this study is to assess the patient-physician relationship in a group of patients with PsA, by using the Perceived Efficacy in Patient-Physician Interactions (PEPPI) and CollaboRATE instruments., Methods: This is a cross-sectional multicenter study where consecutive patients with PsA were enrolled. For each patient, the main demographic, comorbid conditions, and clinical data were collected, including the assessment of disease activity, function, quality of life, and impact of disease. PEPPI and CollaboRATE questionnaires were used, respectively, to evaluate the patient's perception of the patient-physician relationship and the shared decision-making process., Results: A total of 81 patients with PsA were enrolled at four centers in Italy. Overall, our patients showed a high level of confidence in obtaining needed health care, with relatively high median (IQR) values of PEPPI (20; 16-23), and a good shared decision-making process, with high median (IQR) values of CollaboRATE questionnaire (7; 6-9). PEPPI and CollaboRATE scores showed a statistically significant inverse correlation with different clinical variables such as disease duration, Leeds Enthesitis Index, PsA impact of Disease, Health Assessment Questionnaire, pain, patient's global assessment of disease activity and clinical disease activity for PsA. The presence of comorbidities did not appear to be associated with lower values of PEPPI and CollaboRATE., Conclusions: In this study, few patients with PsA were at risk of suboptimal communication with their physician. This phenomenon appeared to be primarily related to higher disease activity and burden., (© 2024. The Author(s).)

Background : High-flow nasal cannula (HFNC) therapy has emerged as a promising treatment modality for interstitial lung disease (ILD)-related respiratory failure. This systematic review aims to evaluate the efficacy and safety of HFNC therapy in patients with ILDs. Methods: A comprehensive literature search was conducted using major electronic databases to identify relevant studies investigating the use of HFNC therapy in ILD patients with respiratory failure. Outcome measures of interest included improvements in oxygenation, dyspnea relief, respiratory rate control, hospital length of stay, and mortality. Results: Twelve studies were analyzed with an overall population of 715 patients included. Idiopathic Pulmonary Fibrosis (IPF) was the most prevalent type of ILD. Evaluated clinical settings were acute (7 studies), chronic (2 studies), and end-stage (3 studies) ILDs. The HFNC as a support for acute respiratory failure seems not inferior to non-invasive ventilation while offering better comfort and patient's perception. Poor data are available about use in chronic/long-term or rehabilitative settings. In end of life/palliative care, an HFNC might improve quality of life. Despite the promising results, further research is warranted to establish optimal HFNC protocols, identify patient subgroups most likely to benefit, and explore long-term outcomes. Conclusions: Overall, the HFNC appears to be a valuable therapeutic option for managing respiratory failure in ILD patients, offering potential improvements in oxygenation and symptom relief.

Benign endobronchial tumors are rare clinical entities characterized by considerable variability in etiology and clinical presentation. The authors report four cases of endobronchial hamartomas treated and followed up from 2018 to 2023. Three of these cases, with identical endobronchial localization in the right lower lobe, were radically treated in flexible bronchoscopy with the only use of biopsy forceps. Another case with a different localization in the left main bronchus was treated with a laser through rigid bronchoscopy. In addition, the authors outline the main interventional pulmonological strategies for the treatment of benign tumors with endobronchial growth based on the existing literature.

The sirtuin family is a heterogeneous group of proteins that play a critical role in many cellular activities. Several degenerative diseases have recently been linked to aberrant sirtuin expression and activity because of the involvement of sirtuins in maintaining cell longevity and their putative antiaging function. Idiopathic pulmonary fibrosis and progressive pulmonary fibrosis associated with systemic autoimmune disorders are severe diseases characterized by premature and accelerated exhaustion and failure of alveolar type II cells combined with aberrant activation of fibroblast proliferative pathways leading to dramatic destruction of lung architecture. The mechanisms underlying alveolar type II cell exhaustion in these disorders are not fully understood. In this review, we have focused on the role of sirtuins in the pathogenesis of idiopathic and secondary pulmonary fibrosis and their potential as biomarkers in the diagnosis and management of fibrotic interstitial lung diseases., (© 2024. The Author(s).)

Background/Objectives : Ultrasound (US) has been progressively spreading as the most useful technique for guiding biopsies and fine-needle aspirations that are performed percutaneously. Malignant pleural mesothelioma (MPM) represents the most common malignant pleural tumour. Thoracoscopy represents the gold standard for diagnosis, although conditions hampering such diagnostic approach often coexist. The Objective was to determine whether ultrasound-guided percutaneous needle biopsy (US-PPNB) has a high diagnostic accuracy and represents a safe option for diagnosis of MPM. Methods: US-PPNB of pleural lesions suspected for MPM in patients admitted from January 2021 to June 2023 have been retrospectively analyzed. An 18-gauge semi-automatic spring-loaded biopsy system (Medax Velox 2 ® ) was used by experienced pneumologists. The obtained specimens were histologically evaluated and defined as adequate or non-adequate for diagnosis according to whether the material was considered appropriate or not for immunohistochemistry (IHC) analysis. The primary objective of the study was the diagnostic yield for a tissue diagnosis. Results: US-PPNB was diagnostic of MPM in 15 out of 18 patients (sensitivity: 83.39%; specificity: 100%; PPV: 100%). Three patients with non-adequate US-PPNB underwent thoracoscopy for diagnosis. We found significant differences in terms of mean pleural lesion thickness between patients with adequate and not-adequate biopsy (15.4 mm (SD: 9.19 mm) and 3.77 mm (SD: 0.60 mm), p < 0.0010. In addition, a significant positive correlation has been observed between diagnostic accuracy and FDG-PET avidity value. Conclusions: US-PPNB performed by a pneumologist represents a valid procedure with a high diagnostic yield and accuracy for the diagnosis of MPM, and may be considered as an alternative option in patients who are not suitable for thoracoscopy.

Background: Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease of unknown aetiology, characterized by the relentless deposition of fibrotic tissue. Biomarkers may play a pivotal role as indicators of disease presence, progression, and treatment response. Sirtuins, a family of enzymes with ADP ribosyltransferase or deacetylase activity, have been implicated in several diseases, including pulmonary fibrosis., Methods: A cross-sectional, prospective, observational single-center study was conducted to investigate the potential role of serum SIRTs levels as biomarkers in patients with IPF. Demographic, clinical, and functional data and serological samples were collected from 34 patients with IPF followed at the Interstital Lung and Rare Diseases Outpatient Clinic of the Vanvitelli Pneumology Clinic, Monaldi Hospital, Naples, Italy and from 19 age-matched controls., Results: Serum SIRT-1 levels were significantly reduced in IPF patients compared to controls (median IPF 667 [435-858] pg/mL versus controls 925 [794-1173] pg/mL; p < 0.001 ). In contrast, serum SIRT-3 levels were significantly increased in IPF patients compared to controls (median IPF 338 [230-500] pg/mL versus controls 154 [99.8-246] pg/mL; p < 0.001). There were no statistically significant differences in serum SIRT-6 and SIRT-7 levels between IPF and controls. In addition, we found a significant positive correlation between SIRT-1 and lung function parameters such as FEV 1 % (ϱ=0.417;p = 0.016), FVC% (ϱ=0.449;p = 0.009) and DL CO % (ϱ=0.393;p = 0.024), while a significant negative correlation was demonstrated between SIR-1 and GAP score, demonstrating a significant reduction in SIRT-1 in advanced Gender-Age-Physiology (GAP) stages 2-3 compared to GAP stage 1 (p = 0.008)., Conclusions: This prospective, cross-sectional study showed that SIRT-1 was associated with lung function and IPF severity and that both SIRT-1 and SIRT-3 could be considered as potential biomarkers of IPF, whereas SIRT-6 and SIRT-7 were not associated with IPF., (© 2024. The Author(s).)

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic-morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical-therapeutic management of the patient.

Objective: The aim was to evaluate the sex differences in sensitivity, specificity, positive and negative predictive values, and likelihood ratio of the outcome indices minimal disease activity (MDA), Disease Activity Score for Psoriatic Arthritis (DAPSA), and Psoriatic Arthritis Impact of Disease (PsAID) with respect to clinical remission, evaluated from both the physician and patient perspective, in a multicenter cohort of patients with PsA., Methods: In this cross-sectional analysis of 2 longitudinal cohorts, all patients with PsA consecutively attending our rheumatology units were considered potentially eligible for the study. In all patients, a complete clinical examination was carried out. The DAPSA was calculated for each patient (DAPSA values ≤ 4 were considered as remission) and MDA was also evaluated. Patient and physician global assessment values ≤ 1 were considered as a surrogate of remission from the patient and physician perspective, respectively., Results: Two hundred seventy-two patients with PsA were enrolled (mean age 55.7 [SD 12.4]; 141 male, 131 female). In both sexes, MDA had good sensitivity and specificity toward remission as assessed by the rheumatologist. Remission according to DAPSA had excellent values of specificity but lacks sensitivity in both sexes. PsAID ≤ 4 had excellent values of sensitivity but lacked specificity in both sexes. Remission defined by DAPSA values was found to be more sensitive and specific in female patients (45.4% and 100%, respectively) than in male patients (33.3% and 84.2%, respectively) with respect to physician-judged remission., Conclusion: The results of this study demonstrate for the first time, to our knowledge, that some differences between the 2 sexes on the different outcome indices are possible. This could be important in the clinical management of patients with PsA., (Copyright © 2024 by the Journal of Rheumatology.)

Interstitial lung diseases comprise a heterogenous range of diffuse lung disorders, potentially resulting in pulmonary fibrosis. While idiopathic pulmonary fibrosis has been recognized as the paradigm of a progressive fibrosing interstitial lung disease, other conditions with a progressive fibrosing phenotype characterized by a significant deterioration of the lung function may lead to a burden of significant symptoms, a reduced quality of life, and increased mortality, despite treatment. There is now evidence indicating that some common underlying biological mechanisms can be shared among different chronic fibrosing disorders; therefore, different biomarkers for disease-activity monitoring and prognostic assessment are under evaluation. Thus, understanding the common pathways that induce the progression of pulmonary fibrosis, comprehending the diversity of these diseases, and identifying new molecular markers and potential therapeutic targets remain highly crucial assignments. The purpose of this review is to examine the main pathological mechanisms regulating the progression of fibrosis in interstitial lung diseases and to provide an overview of potential biomarker and therapeutic options for patients with progressive pulmonary fibrosis.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition, primarily characterized by the presence of a limited airflow, due to abnormalities of the airways and/or alveoli, that often coexists with other chronic diseases such as lung cancer, cardiovascular diseases, and metabolic disorders. Comorbidities are known to pose a challenge in the assessment and effective management of COPD and are also acknowledged to have an important health and economic burden. Local and systemic inflammation have been proposed as having a potential role in explaining the association between COPD and these comorbidities. Considering that the number of patients with COPD is expected to rise, understanding the mechanisms linking COPD with its comorbidities may help to identify new targets for therapeutic purposes based on multi-dimensional assessments.

Objectives: We aimed to evaluate the drug retention rate (DRR) of secukinumab, an anti-IL-17A monoclonal antibody, in patients with psoriatic arthritis (PsA) in a real-life cohort, and to assess the impact of comorbidities and patient clinical characteristics on the DRR of secukinumab., Methods: A retrospective study of prospective followed-up patients was performed to evaluate the DRR of secukinumab on patients with PsA attending the recruiting centres between January 2016 and June 2022., Results: In 207 patients with PsA, a 60-month DRR of secukinumab of 57.0% was estimated (mean time of administration of 21.5±17.1 months). Male gender, age ≥65 years, disease duration ≥5 years and ≥10 years did not influence the DRR of secukinumab. The presence of comorbidities, considering any concomitant disorder, did not affect the DRR of secukinumab. In patients with cardiometabolic multimorbidity, a trend toward a better DRR of secukinumab was recorded. In fact, patients with high blood pressure, dyslipidaemia, and type 2 diabetes showed a trend toward an improved DRR of secukinumab. Furthermore, the presence of obesity did not influence the DRR of secukinumab. Different dosages, previous bDMARDs, and concomitant therapy with csDMARDs did not influence the DRR of secukinumab., Conclusions: A cumulative 60-month DRR of secukinumab of 57.0% in patients with PsA was retrieved. The presence of cardiometabolic multimorbidity could be associated with an improved DRR of secukinumab, whereas obesity did not affect this feature in our cohort. Previous bDMARDs, concomitant csDMARDs, and different drug dosages could not influence the DRR of secukinumab over time.

Competing Interests: Disclosure: There is no conflict of interest or other disclosures.

Interstitial lung diseases (ILDs) are a heterogeneous group of pulmonary disorders characterized by variable degrees of inflammation, interstitial thickening, and fibrosis leading to distortion of the pulmonary architecture and gas exchange impairment. Among them, idiopathic pulmonary fibrosis (IPF) displays the worst prognosis. The only therapeutic options consist of the two antifibrotic drugs, pirfenidone and nintedanib, which limit fibrosis progression but do not reverse the lung damage. The shift of the pathogenetic paradigm from inflammatory disease to epithelium-derived disease has definitively established the primary role of type II alveolar cells, which lose their epithelial phenotype and acquire a mesenchymal phenotype with production of collagen and extracellular matrix (EMC) deposition. Some predisposing environmental and genetic factors (e.g., smoke, pollution, gastroesophageal reflux, variants of telomere and surfactant genes) leading to accelerated senescence set a pro-fibrogentic microenvironment and contribute to the loss of regenerative properties of type II epithelial cells in response to pathogenic noxae. This review provides a complete overview of the different pathogenetic mechanisms leading to the development of IPF. Then, we summarize the currently approved therapies and the main clinical trials ongoing. Finally, we explore the potentialities offered by agents not only interfering with the processes of fibrosis but also restoring the physiological properties of alveolar regeneration, with a particular focus on potentialities and concerns about cell therapies based on mesenchymal stem cells (MSCs), whose anti-inflammatory and immunomodulant properties have been exploited in other fibrotic diseases, such as graft versus host disease (GVHD) and COVID-19-related ARDS.

Competing Interests: We declare no competing interests.

Introduction: The aim of this work is to characterize which Minimal Disease Activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and the different treatment groups was assessed., Methods: We conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age ≥ 18 years, PsA diagnosis, stable treatment for at least 6 months. Patients were grouped depending on the therapy: group 1: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), group 3: Tumor Necrosis Factor α  inhibitors (TNFi), group 4: interleukin inhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4 inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement., Results: A total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area ≤ 3, swollen joint count ≤ 1 and Leeds Enthesitis Index ≤ 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) ≤ 2 cm and pain on visual analogue scale ≤ 1.5 cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4., Conclusions: In each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need. Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA., (© 2023. The Author(s).)

Once thought to be a sterile environment, it is now established that lungs are populated by various microorganisms that participate in maintaining lung function and play an important role in shaping lung immune surveillance. Although our comprehension of the molecular and metabolic interactions between microbes and lung cells is still in its infancy, any event causing a persistent qualitative or quantitative variation in the composition of lung microbiome, termed "dysbiosis", has been virtually associated with many respiratory diseases. A deep understanding of the composition and function of the "healthy" lung microbiota and how dysbiosis can cause or participate in disease progression will be pivotal in finding specific therapies aimed at preventing diseases and restoring lung function. Here, we review lung microbiome dysbiosis in different lung pathologies and the mechanisms by which these bacteria can cause or contribute to the severity of the disease. Furthermore, we describe how different respiratory disorders can be caused by the same pathogen, and that the real pathogenetic mechanism is not only dependent by the presence and amount of the main pathogen but can be shaped by the interaction it can build with other bacteria, fungi, and viruses present in the lung. Understanding the nature of this bacteria crosstalk could further our understanding of each respiratory disease leading to the development of new therapeutic strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psoriatic arthritis (PsA) is a complex and chronic inflammatory condition in which the achievement of the best possible disease control has been proposed as the treatment target, which includes the possibility of reaching remission in all disease domains. However, due to the complexity of this multidomain disease, some patients may still have high disease activity in one or more domain and a high burden of disease, potentially leading to various treatment changes and to difficulty with the overall management. In this paper, we overview the concept of patients with difficult-to-treat PsA and the concept of patients with refractory-to-treatment PsA by providing a distinction between these two concepts and the possible implication for the management of patients with PsA., (© 2023. The Author(s).)

Calcific constrictive pericarditis is a very rare complication of systemic sclerosis. This is the first report of surgically treated calcific constrictive pericarditis in systemic sclerosis. A 53 years-old woman, affected by limited systemic sclerosis, had a diagnosis of calcific constrictive pericarditis. She had a medical history of congestive heart failure since 2022. The patient was treated with pericardiectomy. Via a median sternotomy, the pericardium was dissected and removed from the midline to the left phrenic nerve, thus freeing the heart. Three months after the pericardiectomy, there was a significant clinical improvement. The calcific evolution of chronic pericarditis is a rare complication of systemic sclerosis. This case represents, at best of our knowledge, the first report of calcific constrictive pericarditis, in systemic sclerosis, treated with pericardiectomy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory disease, frequently associated with cardiovascular (CV) comorbidities. Our aim was to compare the prevalence of CV comorbidities between two groups of PsA patients from different European countries: Belgium and Italy., Methods: This is a cross-sectional analysis of two longitudinal cohorts in which 803 PsA patients were enrolled (463 from Belgium and 340 from Italy). All enrolled patients were ≥18 years old and fulfilled the ClASsification criteria for Psoriatic Arthritis (CASPAR criteria). For each patient, demographics, clinical assessments, smoking habits, the presence of arterial hypertension (AH), obesity (BMI ≥30), type 2 diabetes (T2D), CV diseases (acute myocardial infarction, stroke or transient ischaemic attack), dyslipidaemia (Italy only) and hypercholesterolaemia (Belgium only) were collected., Results: The most prevalent comorbidities among Italian patients with PsA were: AH (45.1%), dyslipidaemia (38.6%) and obesity (30.8%), and among Belgian patients were: hypercholesterolaemia (30.9%), obesity (27%) and AH (26.4%). Moreover, the prevalence of T2D and CV diseases was respectively 14.2% and 7.1% among Italian patients and 7.6% and 3.5% among Belgian patients. When comparing the two groups, AH, T2D and CV diseases were significantly more prevalent in Italian PsA patients. After controlling for different confounders, Italian patients, regardless of age, sex, smoking habits, PsA duration, other CV comorbidities, therapy, disease activity and function, had a higher risk to be hypertensive (OR 2.00, p=0.007). Instead of the country in which patients lived was not a predictor for the risk of T2D and CV diseases. Obesity prevalence was not different between the two groups. The lipid profile was unfavourable in both populations (even if not comparable between the two groups, due to the different way of collection), as is often the case in PsA., Conclusions: The prevalence of AH, T2D and CV diseases were higher in Italian patients rather than Belgians. Moreover, among patients with PsA, the risk of AH was higher in the Italian cohort compared to the Belgian cohort. These results suggest that further research is needed to evaluate potential extrinsic factors (geography and sociocultural aspects) that may contribute to CV risk.

Adipose tissue is actually regarded as an endocrine organ, rather than as an organ that merely stores energy. During the COVID-19 pandemic, obesity has undoubtedly emerged as one of the most important risk factors for disease severity and poor outcomes related to SARS-CoV-2 infection. The aberrant production of cytokine-like hormones, called adipokines, may contribute to alterations in metabolism, dysfunction in vascular endothelium and the creation of a state of general chronic inflammation. Moreover, chronic, low-grade inflammation linked to obesity predisposes the host to immunosuppression and excessive cytokine activation. In this respect, understanding the mechanisms that link obesity with the severity of SARS-CoV-2 infection could represent a real game changer in the development of new therapeutic strategies. Our review therefore examines the pathogenic mechanisms of SARS-CoV-2, the implications with visceral adipose tissue and the influences of the adipose tissue and its adipokines on the clinical behavior of COVID-19.

Psoriatic arthritis (PsA) is a chronic inflammatory condition characterized by psoriasis, synovitis, enthesitis, spondylitis, and the possible association with other extra-articular manifestations and comorbidities. It is a multifaceted and systemic disorder sustained by complex pathogenesis, combining aspects of autoinflammation and autoimmunity. Features of PsA autoinflammation include the role of biomechanical stress in the onset and/or exacerbation of the disease; the evidence of involvement of the innate immune response mediators in the skin, peripheral blood and synovial tissue; an equal gender distribution; the clinical course which may encounter periods of prolonged remission and overlapping features with autoinflammatory syndromes. Conversely, the role of autoimmunity is evoked by the association with class I major histocompatibility complex alleles, the polyarticular pattern of the disease which sometimes resembles rheumatoid arthritis and the presence of serum autoantibodies. Genetics also provide important insights into the pathogenesis of PsA, particularly related to class I HLA being associated with psoriasis and PsA. In this review, we provide a comprehensive review of the pathogenesis, genetics and clinical features of PsA that endorse the mixed nature of a disorder at the crossroads of autoinflammation and autoimmunity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psoriatic arthritis (PsA) is a complex, multiform and chronic inflammatory disease characterised by the association of arthritis and psoriasis combined with other related conditions and comorbidities. Treatment of PsA has rapidly evolved by the introduction of new biological drugs and small molecules which allow to achieve disease remission or low disease activity in most of the patients. However, unmet treatment needs still persist for those patients with persistent disease activity or symptoms, impaired function, reduced quality of life or comorbidities. In this context, non-pharmacological approaches, including diet modifications, an adequate sleep quality and physical activity could provide additional benefits. In recent years, diet modifications, improvement of sleep quality and physical activity became an area of interest for researchers and some studies showed how a holistic non-pharmacological approach may ameliorate the quality of life of patients with PsA.The aim of this manuscript was to review the current evidence on the intriguing link and potential effects of diet, sleep and exercise in PsA patients. In particular, we reviewed the literature focusing on the possible benefits of a holistic approach to PsA patients considering lifestyle modifications., Competing Interests: Competing interests: Leuven Research and Development, the technology transfer office of KU Leuven, has received consultancy and speaker fees and research grants on behalf of R.J.L. from Abbvie, Boehringer-Ingelheim, Amgen (formerly Celgene), Eli-Lilly, Galapagos, Janssen, Fresenius Kabi, MSD, Novartis, Pfizer, Biosplice Therapeutics (formerly Samumed), UCB and Viatris., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Rationale: The therapeutic interventions against lung cancer are currently based on a fully personalized approach to the disease with considerable improvement of patients' outcome. Alongside continuous scientific progresses and research investments, massive technologic efforts, innovative challenges, and consolidated achievements together with research investments are at the bases of the engineering and manufacturing revolution that allows a significant gain in clinical setting., Aim and Methods: The scope of this review is thus to focus, rather than on the biologic traits, on the analysis of the precision sensors and novel generation materials, as semiconductors, which are below the clinical development of personalized diagnosis and treatment. In this perspective, a careful revision and analysis of the state of the art of the literature and experimental knowledge is presented., Results: Novel materials are being used in the development of personalized diagnosis and treatment for lung cancer. Among them, semiconductors are used to analyze volatile cancer compounds and allow early disease diagnosis. Moreover, they can be used to generate MEMS which have found an application in advanced imaging techniques as well as in drug delivery devices., Conclusions: Overall, these issues represent critical issues only partially known and generally underestimated by the clinical community. These novel micro-technology-based biosensing devices, based on the use of molecules at atomic concentrations, are crucial for clinical innovation since they have allowed the recent significant advances in cancer biology deciphering as well as in disease detection and therapy. There is an urgent need to create a stronger dialogue between technologists, basic researchers, and clinicians to address all scientific and manufacturing efforts towards a real improvement in patients' outcome. Here, great attention is focused on their application against lung cancer, from their exploitations in translational research to their application in diagnosis and treatment development, to ensure early diagnosis and better clinical outcomes.

Objective: To assess any differences and similarities in psoriatic arthritis (PsA) between sexes. Any possible differences of psoriasis and its potential impact on disease burden between sexes with PsA were also evaluated., Methods: Cross-sectional analysis of two longitudinal PsA cohorts. The impact of psoriasis on the PtGA was evaluated. Patients were stratified in four groups based on BSA. The median PtGA was then compared between the four groups. Moreover, a multivariate linear regression analysis was performed in order to evaluate associations between PtGA and skin involvement, split by sexes., Results: We enrolled 141 males and 131 females: PtGA, PtPnV, tender, swollen joint count, DAPSA, HAQ-DI, PsAID-12 were statistically significant higher in females (p ≤ 0.05). PASS "yes" was deemed more in males than in females and BSA was higher in males. MDA was present more in males than females. When the patients were stratified on BSA, median PtGA was not different between males and females with BSA = 0. Instead, in females with BSA > 0, a higher PtGA was observed compared to males with BSA > 0. There was not a statistically significant association between skin involvement and PtGA at linear regression analysis, even if a trend seems to be present in female., Conclusions: Psoriasis is more present in males, but it seems to be related to a worse impact in females. In particular, a possible role of psoriasis as an influencing factor the PtGA was found. Moreover, female PsA patients tended to have more disease activity, worse function, and higher disease burden., (© 2023. The Author(s).)

The aims of this study were as follows: (1) To evaluate the entheseal fibrocartilage (EF) during Achilles tendon insertion in patients with Psoriatic Arthritis (PsA) by using power Doppler ultrasound (PDUS), (2) to assess the intra and inter-reader reliability of the evaluation of EF thickness, (3) to compare the EF thickness of PsA patients, athletes and healthy controls (HCs), and (4) to evaluate the correlations between EF abnormalities, disease activity and functional indices in PsA., Methods: Consecutive PsA patients attending our unit were asked to participate. HCs and agonist athletes were enrolled as a control group. A bilateral PDUS evaluation of Achilles tendons was performed in order to evaluate the EF in all patients and controls., Results: In total, 30 PsA patients, 40 athletes and 20 HCs were enrolled. The median (IQR) EF thickness among the PsA patients, athletes and HCs was 0.035 cm (0.028-0.04) cm, 0.036 (0.025-0.043) cm and 0.030 (0.020-0.038) cm, respectively ( p = 0.05 between PsA patients and HCs). The intra-reader reliability was excellent [ICC (95% CI) of 0.91 (0.88-0.95)] and the inter-reader reliability was good (0.80 (0.71-0.86). The assessment of EF was feasible, with a mean time of 2 min. No correlations were found with disease activity indices in PsA patients., Conclusion: The assessment of EF is a feasible and reproducible test and may be explored as a potential imaging biomarker.

Chronic obstructive pulmonary disease (COPD) is characterized by respiratory symptoms and non-reversible airflow limitation with recurrent episodes of acute exacerbations. The concurrent presence of bronchiectasis in patients with COPD is associated with reduced respiratory function as well as increased exacerbation risk. Adiponectin is a promising biomarker in COPD, as greater high molecular weight (HMW) oligomer levels have been observed among COPD patients. Here, we investigate adiponectin levels in two groups of COPD patients characterized by the presence or absence of bronchiectasis (BCO), comparing both groups to healthy controls. We evaluated serum adiponectin levels in COPD patients, those with BCO, and healthy subjects and characterized the pattern of circulating adiponectin oligomers. We found that forced volume capacity % (FVC%) and forced expiratory volume % (FEV1%) were lower for BCO patients than for COPD patients. COPD patients had higher levels of adiponectin and its HMW oligomers than healthy controls. Interestingly, BCO patients had higher levels of adiponectin than COPD patients. We showed that expression levels of IL-2, -4, and -8, IFN-γ, and GM-CSF were significantly higher in BCO patients than in healthy controls. Conversely, IL-10 expression levels were lower in BCO patients. Our data suggest that the increased levels of adiponectin detected in the cohort of BCO patients compared to those in COPD patients without bronchiectasis might be determined by their worse airway inflammatory state. This hypothesis suggests that adiponectin could be considered as a biomarker to recognize advanced COPD patients with bronchiectasis.

Obesity, through adipose tissue (AT) inflammation and dysregulation, represents a critical factor for COVID-19; here, we investigated whether serum levels of adiponectin, HMW oligomers, leptin, and resistin are modulated and/or correlated with clinical and biochemical parameters of severe COVID-19 patients. This study included 62 severe COVID-19 patients; 62 age and sex-matched healthy subjects were recruited as a control group. Anthropometric and biochemical parameters were obtained and compared. Adiponectin, HMW oligomers, leptin, and resistin were analyzed by ELISA. The adiponectin oligomerization state was visualized by Western blotting. When compared to healthy subjects, total adiponectin levels were statistically lower in severe COVID-19 while, in contrast, the levels of leptin and resistin were statistically higher. Interestingly, HMW adiponectin oligomers negatively correlated with leptin and were positively associated with LUS scores. Resistin showed a positive association with IL-6, IL-2R, and KL-6. Our data strongly support that adipose tissue might play a functional role in COVID-19. Although it needs to be confirmed in larger cohorts, adiponectin HMW oligomers might represent a laboratory resource to predict patient seriousness. Whether adipokines can be integrated as a potential additional tool in the evolving landscape of biomarkers for the COVID-19 disease is still a matter of debate. Other studies are needed to understand the molecular mechanisms behind adipokine's involvement in COVID-19.

COVID-19 is an infective disease resulting in widespread respiratory and non-respiratory symptoms prompted by SARS-CoV-2 infection. Interaction between SARS-CoV-2 and host cell receptors prompts activation of pro-inflammatory pathways which are involved in epithelial and endothelial damage mechanisms even after viral clearance. Since inflammation has been recognized as a critical step in COVID-19, anti-inflammatory therapies, including both steroids and non-steroids as well as cytokine inhibitors, have been proposed. Early treatment of COVID-19 has the potential to affect the clinical course of the disease regardless of underlying comorbid conditions. Non-steroidal anti-inflammatory drugs (NSAIDs), which are widely used for symptomatic relief of upper airway infections, became the mainstay of early phase treatment of COVID-19. In this review, we discuss the current evidence for using NSAIDs in early phases of SARS-CoV-2 infection with focus on ketoprofen lysine salt based on its pharmacodynamic and pharmacokinetic features.

Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancer cases. Stage III NSCLC represents a highly heterogenous stage characterized by different disease presentations and a wide range of treatment options. For patients with good performance status and unresectable-stage III NSCLC with programmed death-ligands 1 (PD-L1) tumor proportion score (TPS) ≥1%, durvalumab consolidation immunotherapy after a platinum-based chemo-radiotherapy is strongly recommended. However, age, poor performance status, underlying comorbidities may represent contraindications for chemotherapy to be used in a subgroup of patients. Herein, we report a case of an 80-year-old male affected by a stage IIIB lung adenocarcinoma with overexpression of PD-L1 (TPS 90%) treated with pembrolizumab, an immune checkpoint inhibitor targeting PD-1/PD-L1 pathways, which shows a complete resolution of lung lesion after four cycles of treatment. Although randomized controlled trials are required, this case report may suggest the potential role of pembrolizumab for chemotherapy unsuitable patients with overexpressing PD-L1 unresectable-stage III NSCLC.

SARS-CoV-2 infection can induce a broad range of clinical symptoms, and the most severe cases are characterized by an uncontrolled inflammatory response with the overproduction of proinflammatory cytokines. Elevated levels of C-reactive protein, interleukin-1B, and interleukin-6 have become key signatures of severe COVID-19. For this reason, the use of 6 mg of dexamethasone has become a standard of care, although this regime may not be optimal. Even though various glucocorticoid doses have been proposed, it is still unclear which dose should be used to prevent adverse effects while at the same time reducing the inflammatory response. Here, we compared two different doses of corticosteroids in 52 elderly hospitalized patients with severe to critical COVID-19 to assess efficacy and safety. We showed that in patients receiving a higher dose of prednisone, the time to negative swab was significantly longer. Furthermore, although neither dose was correlated with the risk of death, patients receiving the high dose were more likely to have adverse events such as hyperglycemia, leukocytosis, an increase in systemic blood pressure, and others. Finally, the BMI, WBC number, and NLR value were directly related to death. In conclusion, although the optimal glucocorticoid dose is still undefined, our retrospective study supports the absence of beneficial effects in the utilization of higher doses of corticosteroids in elderly patients with severe to critical COVID-19.

SARS-CoV-2 infection leads to a heterogenous spectrum of clinical conditions ranging from self-limiting upper airway infection to severe respiratory failure. Carbocysteine is a thioether mucolytic with antioxidant and anti-inflammatory activities. Carbocysteine has been shown to have anti-viral effects on human rhinovirus, RSV and the influenza virus as well as interfering with upper airway ciliary motility, the first site of SARS-CoV-2 infection, leading to more effective mucus clearance and potential containment of viral spread towards the lower airway. Positive effects, in terms of limiting superimposed bacterial infection and reducing oxidative stress, have also been documented in COPD patients. Accordingly, Carbocysteine should also be considered in both post-exposure prophylaxis and early-phase treatment of COVID-19 in combination with other agents (monoclonal antibodies, antivirals, non-steroidal anti-inflammatory agents, and inhaled corticosteroids). In this review, we explored the pharmacokinetic and pharmacodynamic aspects of Carbocysteine to delineate its potential therapeutic impact in patients with COVID-19., Competing Interests: The authors declare no conflict of interest

Introduction: Many data already suggested that cancer and IPF are underlined by a number of common pathogenic biologic pathways. However, fewer data regards the interconnections, in terms of synergy or increased toxicities, of drugs used in cancer and IPF. Particularly, how the specific therapy influences the concurrent condition and prognostic factors of response in patients with both lung cancer and IPF are far to be clarified. Similarly, identification of features of IPF patients with higher risk of developing pulmonary adverse events when treated with chemotherapy, immune checkpoint inhibitors, TKIs, or radiotherapy is of primary importance in clinical practice., Areas Covered: We will discuss the scientific rationale, based on the extensive analysis of literature data, by consulting several databases for combining anticancer and antifibrotic treatments and for the design of novel therapeutic strategies. The role of immunotherapy in cancer aroused in IPF context will be discussed with specific interested, based on the continuously increasing role of immune checkpoint inhibition against lung tumors., Expert Opinion: This work will help to improve knowledge, based on a multidisciplinary perspective, on IPF and cancer patients, which identify an unmet clinical need. A better management during each phase of disease progression will require the design innovative trials and the development of new drugs and molecules both in the oncologic and respiratory medicine pipeline.

Alectinib is a highly selective tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that is approved as first-line treatment in adult patients with ALK-positive non-small cell lung cancer (NSCLC) and as second-line in patients previously treated with crizotinib, and has been shown in the literature to significantly prolong progression-free survival compared to chemotherapy in patients with advanced non-small cell lung cancer. The authors describe a clinical case of a 24-year-old woman with malignant massive pleural effusion caused by ALK rearranged pulmonary adenocarcinoma with pleural and pericardial metastasis, in which, despite a dramatic clinical debut, the correct and timely management of the diagnostic and therapeutic path allowed for extraordinary therapeutic success.

Objectives: To stratify psoriatic arthritis (PsA) patients based on psoriasis (PsO) onset age: early onset psoriasis (EOP) vs. late onset psoriasis (LOP), and to assess if there are differences in disease characteristics, activity/function/impact of the disease, and comorbidity indices., Methods: Cross-sectional analysis of a longitudinal PsA cohort. Patients were stratified based on PsO onset age., Results: One hundred and sixty PsA patients were enrolled (84 in EOP and 76 in LOP group) in the study. EOP PsA patients seem to have an increased probability to have dactylitis rather than LOP ones, OR 9.64 (3.77-24.6). Comorbidity indices (Rheumatic Disease Comorbidity Index and Charlson Comorbidity Index) were higher in LOP PsA patients, but these data were not confirmed when adjusted by age and sex. There are also differences in the treatment regimen: EOP PsA patients were more frequently treated with anti-interleukin (IL) 17; instead, LOP patients were more frequently treated with non-steroid anti-inflammatory drugs and conventional synthetic disease-modifying anti-rheumatics drugs. There were no differences in the disease activity, function, or impact of the disease., Conclusions: There are some clinical and therapeutic differences in PsA patients linked to the PsO onset age, namely dactylitis in EOP. Other characteristics found were: a "comorbidities trend" in LOP patients and a more frequent use of anti-IL17 in EOP., (© 2022. The Author(s).)

Background: Previous studies regarding the prevalence of frailty in patients with lung cancer and mortality in frail patients with lung cancer are inconsistent and require clarification., Research Question: What is the prevalence and impact of frailty in patients with lung cancer?, Study Design and Methods: This systematic review and meta-analysis used a combination of free-text terms and medical subject headings terms, according to the database requirements in MEDLINE/PubMed, Scopus, and Cochrane Library from inception until November 15, 2020., Results: A total of 2,571 articles were identified, and 16 articles involving 4,183 patients were included for study. The prevalence of frailty in lung cancer was 45% (95% CI, 28-61; I 2  = 99.5%; P < .0001). In patients with lung cancer, frailty was associated with an increased hazard ratio for mortality (hazard ratio, 3.01; 95% CI, 1.77-5.10; P < .001)., Interpretation: The prevalence of frailty in lung cancer is 45%, which has a significant negative impact on survival of patients with lung cancer. These results highlight the importance of measuring frailty, which provides important prognostic information, and may provide opportunities for interventions to improve outcomes in patients with lung cancer., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: The EULAR group recently published the definition of difficult-to-treat (D2T) patients for rheumatoid arthritis. However, a similar definition is lacking for patients with psoriatic arthritis (PsA), in which its multi-domain expression may impact the treatment response. The aim of the study was to characterize the potential D2T PsA patients, to assess the risk factors, and to determine the burden of disease., Methods: Retrospective analysis of a longitudinal cohort of PsA patients attending a tertiary care center. At each visit, the patients underwent a complete physical examination and the clinical/laboratory data were collected. Data on comorbidities with the assessment of different comorbidity indices were also collected. Disease activity was assessed by using the DAPSA score and the MDA. The PsAID and HAQ-DI were also collected. We use the previous identified definition of D2T patients, applied to our PsA group and modified for this study., Results: A total of 106 patients fulfilled the inclusion criteria and were evaluated. Of these, 36 (33.9%) patients fulfilled the criteria for the potential D2T patients. D2T patients showed a significantly higher BMI and higher prevalence of fibromyalgia. Furthermore, D2T patients showed a significantly higher median Functional Comorbidity Index and a significantly higher BSA, LEI, pain level, PsAID score, and HAQ-DI than non-D2T patients. Potential D2T patients also showed a significant delay in the time from diagnosis to first b/ts DMARDs treatment., Conclusions: Our study firstly evaluated the presence of clinical characteristics of potential D2T patients and may contribute to future research on this intriguing aspect., (© 2022. The Author(s).)

COVID-19 encompasses a broad spectrum of clinical conditions caused by SARS-CoV-2 infection. More severe cases experience acute respiratory and/or multiorgan failure. KL-6 is a glycoprotein expressed mainly from type II alveolar cells with pro-fibrotic properties. Serum KL-6 concentrations have been found in patients with COVID-19. However, the relevance of KL-6 in patients with severe and critical COVID-19 has not been fully elucidated. Methods: Retrospective data from consecutive severe to critical COVID-19 patients were collected at UOC Clinica Pnuemologica “Vanvitelli”, A.O. dei Colli, Naples, Italy. The study included patients with a positive rhinopharyngeal swab for SARS-CoV-2 RNA with severe or critical COVID-19. Results: Among 87 patients, 24 had poor outcomes. The median KL-6 value in survivors was significantly lower when compared with dead or intubated patients (530 U/mL versus 1069 U/mL p < 0.001). KL-6 was correlated with body mass index (BMI) (r: 0.279, p: 0.009), lung ultrasound score (LUS) (r: 0.429, p < 0.001), Chung Score (r: 0.390, p < 0.001). KL-6 was associated with the risk of death or oro-tracheal intubation (IOT) after adjusting for gender, BMI, Charlson Index, Chung Score, and PaO2/FIO2 (OR 1.003 95% CI 1.001−1.004, p < 0.001). Serum KL-6 value of 968 has a sensitivity of 79.2%, specificity of 87.1%, PPV 70.4%, NPV 91.5%, AUC: O.85 for risk of death or IOT. Conclusions: The presented research highlights the relevance of serum KL-6 in severe to critical COVID-19 patients in predicting the risk of death or IOT., Competing Interests: The authors declare no conflict of interest.

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) represent leading causes of morbidity and mortality worldwide. Common risk factors lead to an increased inflammatory response, enhances oxidative stress, and changes in lung microenvironment contributing to fine-tuned interaction between these respiratory disorders. Despite evidence that COPD represents a main risk factor for LC, assessment of LC risk features among COPD patients is not routinely considered in the clinical practice. In LC patients concurrent COPD may impact on clinical scenario influencing the response to treatment. Better understanding LC and COPD coexistence may impact on clinical scenario influencing therapeutic approach. In this review, we describe the basis of this network and how the complex interplay between these respiratory disorders affects the clinical decision-making process.

The endothelium is composed of a monolayer of endothelial cells, lining the interior surface of blood and lymphatic vessels. Endothelial cells display important homeostatic functions, since they are able to respond to humoral and hemodynamic stimuli. Thus, endothelial dysfunction has been proposed as a key and early pathogenic mechanism in many clinical conditions. Given the relevant repercussions on cardiovascular risk, the complex interplay between endothelial dysfunction and systemic arterial hypertension has been a matter of study in recent years. Numerous articles have been published on this issue, all of which contribute to providing an interesting insight into the molecular mechanisms of endothelial dysfunction in arterial hypertension and its role as a biomarker of inflammation, oxidative stress, and vascular disease. The prognostic and therapeutic implications of endothelial dysfunction have also been analyzed in this clinical setting, with interesting new findings and potential applications in clinical practice and future research. The aim of this review is to summarize the pathophysiology of the relationship between endothelial dysfunction and systemic arterial hypertension, with a focus on the personalized pharmacological and rehabilitation strategies targeting endothelial dysfunction while treating hypertension and cardiovascular comorbidities.

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease belonging to the axial spondyloarthritis (axSpA), a group of diseases that affects the axial skeleton and causes severe pain and disability. An early diagnosis and appropriate treatment can reduce the severity of the disease and the risk of progression. TNF-α inhibitors demonstrated efficacy and effectiveness in axSpA patients by reducing disease activity, minimizing inflammation and improving the quality of life. More recently, new insights in pathogenesis of axSpA, including the discovery of the role of IL-23/IL-17 axis and intracellular pathways, led to the development of new biologics and small molecules that improve our therapeutic armamentarium. New alternatives are also being soon available. The aim of this paper is to narratively review the recent insights and future prospects in the treatment of AS and, more in general, axSpA., Competing Interests: The authors declare that they have no conflicts of interest related to the work., (© 2022 Perrotta et al.)

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray-scale (GS; B-mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS- and PD-mode changes was found in 90% and 59.3% of PsA patients ( n = 140) and 62.7% and 35.3% of FMS patients ( n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B- and PD-mode, respectively, 3.5 being the best cut-off GS-score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B-mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B-mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS.

Introduction: MRI allows a better evaluation of inflammatory and structural lesions of the sacroiliac joints and spine in patients with axial spondyloarthritis (axial SpA), so MRI plays an important role in the classification and diagnosis of axial SpA. The aim of our study was to assess extra-axial MRI findings at pelvic sites and their possible associations with clinical indices in patients with axial SpA., Methods: Axial-SpA patients who were classified according to the ASAS criteria and consecutively attended our clinic were assessed with pelvic MRI. The main clinical and demographic characteristics of all patients, including age, sex, BMI, presence of HLA-B27 and type of axial SpA (radiographic or nonradiographic), were evaluated. The main indices of disease activity and joint function were assessed, including BASDAI, ASDAS-PCR, BASMI and BASFI. Finally, the presence/absence of inflammatory/structural lesions at extra-axial structures (the hip joints, pubic symphysis, greater and lesser trochanters, ischial tuberosity, iliac spines and iliac crest) was evaluated., Results: 35 patients (21 males and 14 females) with a mean age (SD) of 47 (12.7) years and a mean duration of symptoms of 5 (2.1) years were enrolled. Hip abnormalities were found in 14 (40%) patients. Trochanteric enthesopathy/bursitis and pubic osteitis were found in 2 patients (5.7%) and 1 patient (2.8%), respectively. No other abnormalities were found at other sites. We found significant associations between the presence of extra-axial alterations, disease activity and joint function., Conclusions: Our study demonstrated the presence of extra-axial abnormalities in more than one-third of patients with axial SpA, suggesting that MRI evaluation should be extended to the entire pelvis., (© 2021. The Author(s).)