Pirfenidone and Nintedanib in Pulmonary Fibrosis: Lights and Shadows.

Pirfenidone and Nintedanib are specific drugs used against idiopathic pulmonary fibrosis (IPF) that showed efficacy in non-IPF fibrosing interstitial lung diseases (ILD). Both drugs have side effects that affect patients in different ways and have different levels of severity, making treatment even more challenging for patients and clinicians. The present review aims to assess the effectiveness and potential complications of Pirfenidone and Nintedanib treatment regimens across various ILD diseases. A detailed search was performed in relevant articles published between 2018 and 2023 listed in PubMed, UpToDate, Google Scholar, and ResearchGate, supplemented with manual research. The following keywords were searched in the databases in all possible combinations: Nintedanib; Pirfenidone, interstitial lung disease, and idiopathic pulmonary fibrosis. The most widely accepted method for evaluating the progression of ILD is through the decline in forced vital capacity (FVC), as determined by respiratory function tests. Specifically, a decrease in FVC over a 6-12-month period correlates directly with increased mortality rates. Antifibrotic drugs Pirfenidone and Nintedanib have been extensively validated; however, some patients reported several side effects, predominantly gastrointestinal symptoms (such as diarrhea, dyspepsia, and vomiting), as well as photosensitivity and skin rashes, particularly associated with Pirfenidone. In cases where the side effects are extremely severe and are more threatening than the disease itself, the treatment has to be discontinued. However, further research is needed to optimize the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. Finally, other studies are requested to establish the treatments that can stop ILD progression.

Vascular Endothelial Damage in COPD: Where Are We Now, Where Will We Go?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has higher rates among the general population, so early identification and prevention is the goal. The mechanisms of COPD development have not been completely established, although it has been demonstrated that endothelial dysfunction plays an important role. However, to date, the measurement of endothelial dysfunction is still invasive or not fully established. Nailfold video capillaroscopy (NVC) is a safe, non-invasive diagnostic tool that can be used to easily evaluate the microcirculation and can show any possible endothelial dysfunctions early on. The aim of this review is to evaluate if nailfold microcirculation abnormalities can reflect altered pulmonary vasculature and can predict the risk of cardiovascular comorbidities in COPD patients. METHODS: A systematic literature search concerning COPD was performed in electronic databases (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until March 2024. The following search words were searched in the databases in all possible combinations: chronic obstructive pulmonary disease (COPD), endothelial damage, vascular impairment, functional evaluation, capillaroscopy, video capillaroscopy, nailfold video capillaroscopy. Only manuscripts written in English were considered for this review. Papers were included only if they were able to define a relationship between COPD and endothelium dysfunction. RESULTS: The search selected 10 articles, and among these, only three previous reviews were available. Retinal vessel imaging, flow-mediated dilation (FMD), and skin autofluorescence (AF) are reported as the most valuable methods for assessing endothelial dysfunction in COPD patients. CONCLUSIONS: It has been assumed that decreased nitric oxide (NO) levels leads to microvascular damage in COPD patients. This finding allows us to assume NVC's potential effectiveness in COPD patients. However, this potential link is based on assumption; further investigations are needed to confirm this hypothesis.

Oscillometry Longitudinal Data on COVID-19 Acute Respiratory Syndrome Treated with Non-Invasive Respiratory Support.

Background: Oscillometry allows for the non-invasive measurements of lung mechanics. In COVID-19 ARDS patients treated with Non-Invasive Oxygen Support (NI-OS), we aimed to (1) observe lung mechanics at the patients' admission and their subsequent changes, (2) compare lung mechanics with clinical and imaging data, and (3) evaluate whether lung mechanics helps to predict clinical outcomes. Methods: We retrospectively analyzed the data from 37 consecutive patients with moderate-severe COVID-19 ARDS. Oscillometry was performed on their 1st, 4th, and 7th day of hospitalization. Resistance (R5), reactance (X5), within-breath reactance changes (ΔX5), and the frequency dependence of the resistance (R5-R19) were considered. Twenty-seven patients underwent computed tomographic pulmonary angiography (CTPA): collapsed, poorly aerated, and normally inflated areas were quantified. Adverse outcomes were defined as intubation or death. Results: Thirty-two patients were included in this study. At the first measurement, only 44% of them had an abnormal R5 or X5. In total, 23 patients had measurements performed on their 3rd day and 7 on their 7th day of hospitalization. In general, their R5, R5-R19, and ΔX decreased with time, while their X5 increased. Collapsed areas on the CTPA correlated with the X5 z-score (ρ = -0.38; p = 0.046), while poorly aerated areas did not. Seven patients had adverse outcomes but did not present different oscillometry parameters on their 1st day of hospitalization. Conclusions: Our study confirms the feasibility of oscillometry in critically ill patients with COVID-19 pneumonia undergoing NI-OS. The X5 z-scores indicates collapsed but not poorly aerated lung areas in COVID-19 pneumonia. Our data, which show a severe impairment of gas exchange despite normal reactance in most patients with COVID-19 ARDS, support the hypothesis of a composite COVID-19 ARDS physiopathology.

Cardiopulmonary exercise testing complements both spirometry and nuclear imaging for assessing sarcoidosis stage and for monitoring disease activity.

BACKGROUND: Pulmonary sarcoidosis is a systemic disease that can confound established follow-up tools. Pulmonary function tests (PFTs) are recommended in initial and follow-up patient evaluations yet are imperfect predictors of disease progression. The cardiopulmonary exercise test (CPET) is another potentially useful monitoring tool, although previous studies report conflicting findings regarding which variables are altered by the disease. Nuclear imaging tests are also employed to assess inflammatory activity and may be predictive of functional deterioration. AIM: We asked whether PFTs or CPET are more diagnostic of disease stage, which subsets of functional variables are impacted by the disease, and how these relate to nuclear imaging signs of active inflammation. STUDY DESIGN AND METHODS: We collected retrospective data (spirometry, CPET, Gallium-67 scintigraphy, 18F-FDG PET/CT) from 48 patients and 10 controls. Disease severity was assessed following Scadding classification. First, we correlated individual PFTs and CPET parameters to Scadding stage and nuclear imaging data. Next, we performed Principal Component Analysis (PCA) on PFTs and CPET parameters, separated into respiratory, cardiovascular and metabolic subsets. Finally, we constructed multiple regression models to determine which variable subsets were the best predictors of Scadding stage and disease activity. RESULTS: The majority of PFTs and CPET single parameters were significantly correlated with patient stage, while only few correlated with disease activity. Nevertheless, multiple regression models were able to significantly relate PFTs and CPET to both disease stage and activity. Additionally, these analyses highlighted CPET cardiovascular parameters as the best overall predictors of disease stage and activity. CONCLUSIONS: Our results display how CPET and spirometry data complement each other for sarcoidosis disease staging, and how these tests are able to detect disease activity. Our findings suggest that CPET, a repeatable and non-invasive functional test, should be more routinely performed and taken into account in sarcoidosis patient follow-up.

Patients' unmet needs and treatment preferences concerning digital ulcers in systemic sclerosis.

INTRODUCTION: Digital ulcers (DUs) significantly impact on quality of life and function in patients with systemic sclerosis (SSc). The aim of our survey was to explore patients' perspectives and their unmet needs concerning SSc-DUs. MATERIALS: SSc patients were invited through international patient associations and social media to participate in an online survey. RESULTS: 358 responses were obtained from 34 countries: US (65.6%), UK (11.5%) and Canada (4.5%). Recurrent DUs are common: >10 DUs (46.1%), 5-10 DUs (21.5%), 1-5 DUs (28.5%), 1 DU (3.9%). Fingertip DUs were most frequent (84.9%), followed by those overlying the interphalangeal joints (50.8%). The impact of DUs in patients is broad, from broad-ranging emotional impacts to impact on activities of daily living, and personal relationships. Half (51.7%) of respondents reported that they received wound/ulcer care, most often provided by non-specialist wound care clinics (63.8%). There was significant variation in local (wound) DU care, in particular the use of debridement and pain management. DU-related education was only provided to one-third of patients. One-quarter (24.6%) were 'very satisfied' or 'satisfied' that the provided DU treatment(s) relieved their DU symptoms. Pain, limited hand function, and ulcer duration/chronicity were the main reasons for patients to consider changing DU treatment. CONCLUSIONS: Our data show that there is a large variation in DU treatment between countries. Patient access to specialist wound-care services is limited and only a small proportion of patients had their DU needs met. Moreover, patient education is often neglected. Evidence-based treatment pathways are urgently needed for DU management.

A multi-national survey to identify clinicians' perspectives concerning Proton Pump inhibitors in patients with systemic sclerosis.

OBJECTIVES: Proton Pump Inhibitors (PPIs) are widely used in SSc for gastroesophageal reflux disease (GERD). However, there is little evidence to support their empirical use and long-term safety has been questioned. Our objective was to better describe clinicians' attitudes toward PPIs prescription and use in SSc patients. METHODS: Clinicians involved in the care of SSc patients were invited through international physician networks and social media to participate in an online survey. RESULTS: Responses from 227 clinicians from 36 countries were evaluable. The majority 'agreed' (41.4 %) or 'strongly agreed' (45.4 %) that GERD is a major cause of morbidity in SSc. Lifestyle modifications are seldom (16 %) considered effective. Only half 'agreed' (43 %) or 'strongly agreed' (11 %) there is solid evidence supporting PPIs efficacy in SSc. The most common reasons for PPIs prescription were symptomatic GERD unresponsive to lifestyle modification (95 %), objective evidence of GERD (82 %), and hoarseness or respiratory symptoms (71 %). There are variable concerns about PPIs long-term safety in SSc. The three highest (mean) reasons (0-10, here 10 is 'very concerned') were: small intestinal bacterial overgrowth (5.5), osteoporosis (5.4), and drug interactions (5.2). There are significant differences in attitudes towards surgery for refractory GERD, and concerns about potential complications. PPIs may have a putative role for disease modification (e.g., ILD and calcinosis), and the role of immunosuppression is uncertain for GI (gastrointestinal) disease in SSc. CONCLUSION: PPIs are frequently prescribed in SSc. Side effects are a recognized concern, especially regarding long-term therapy. There is significant variation in attitudes towards surgical intervention. Future research and practical treatment recommendation for PPIs in SSc are urgently needed.

Nailfold Capillaroscopy Analysis Can Add a New Perspective to Biomarker Research in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA), all of which are characterised by inflammation of small-medium-sized vessels. Progressive understanding of these diseases has allowed researchers and clinicians to start discussing nailfold video capillaroscopy (NVC) as a future tool for many applications in daily practice. Today, NVC plays a well-established and validated role in differentiating primary from secondary Raynaud's phenomenon correlated with scleroderma. Nevertheless, there has not been sufficient attention paid to its real potential in the ANCA-associated vasculitis. In fact, the role of NVC in vasculitis has never been defined and studied in a multicentre and multinational study. In this review, we carried out a literature analysis to identify and synthesise the possible role of capillaroscopy for patients with ANCA-associated vasculitis. METHODS: Critical research was performed in the electronic archive (PUBMED, UpToDate, Google Scholar, ResearchGate), supplemented with manual research. We searched in these databases for articles published until November 2023. The following search words were searched in the databases in all possible combinations: capillaroscopy, video capillaroscopy, nailfold-video capillaroscopy, ANCA-associated vasculitis, vasculitis, granulomatosis with polyangiitis, EGPA, and microscopic polyangiitis. RESULTS: The search identified 102 unique search results. After the evaluation, eight articles were selected for further study. The literature reported that capillaroscopy investigations documented non-specific abnormalities in 70-80% of AAV patients. Several patients showed neoangiogenesis, capillary loss, microhaemorrhages, and bushy and enlarged capillaries as the most frequent findings. Furthermore, the difference between active phase and non-active phase in AAV patients was clearly discernible. The non-active phase showed similar rates of capillaroscopy alterations compared to the healthy subjects, but the active phase had higher rates in almost all common abnormalities instead. CONCLUSIONS: Microvascular nailfold changes, observed in patients affected by vasculitis, may correlate with the outcome of these patients. However, these non-specific abnormalities may help in the diagnosis of vasculitis. As such, new analysis analyses are necessary to confirm our results.

Functional Progression after Dose Suspension or Discontinuation of Nintedanib in Idiopathic Pulmonary Fibrosis: A Real-Life Multicentre Study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with rapidly progressive evolution and an unfavorable outcome. Nintedanib (NTD) is an antifibrotic drug that has been shown to be effective in slowing down the progression of the disease. The aim of our study was to examine the efficacy, especially in terms of the functional decline, and the safety profile of NTD in patients treated with the recommended dose and subjects who reduced or suspended the therapy due to the occurrence of adverse reactions. METHODS: We conducted a real-life retrospective study based on the experience of NTD use in two centers between 2015 and 2022. Clinical data were evaluated at baseline, at 6 and 12 months after the NTD introduction in the whole population and in subgroups of patients who continued the full-dose treatment, at a reduced dosage, and at the discontinuation of treatment. The following data were recorded: the demographic features, IPF clinical features, NTD therapeutic dosage, tolerability and adverse events, pulmonary function tests (PFTs), the duration of treatment upon discontinuation, and the causes of interruption. RESULTS: There were 54 IPF patients who were included (29.6% females, with a median (IQR) age at baseline of 75 (69.0-79.0) years). Twelve months after the introduction of the NTD therapy, 20 (37%) patients were still taking the full dose, 11 (20.4%) had reduced it to 200 mg daily, and 15 (27.8%) had stopped treatment. Gastrointestinal intolerance predominantly led to the dose reduction (13.0%) and treatment cessation (20.4%). There were two deaths within the initial 6 months (3.7%) and seven (13.0%) within 12 months. Compared to the baseline, the results of the PFTs remained stable at 6 and 12 months for the entire NTD-treated population, except for a significant decline in the DLCO (% predicted value) at both 6 (38.0 ± 17.8 vs. 43.0 ± 26.0; p = 0.041) and 12 months (41.5 ± 15.3 vs. 44.0 ± 26.8; p = 0.048). The patients who continued treatment at the full dose or a reduced dosage showed no significant differences in the FVC and the DLCO at 12 months. Conversely, those discontinuing the NTD exhibited a statistically significant decline in the FVC (% predicted value) at 12 months compared to the baseline (55.0 ± 13.5 vs. 70.0 ± 23.0; p = 0.035). CONCLUSIONS: This study highlights the functional decline of the FVC at 12 months after the NTD initiation among patients discontinuing therapy but not among those reducing their dosage.

Robustness of Longitudinal Safety and Efficacy After Paclitaxel-Based Endovascular Therapy for Treatment of Femoro-Popliteal Artery Occlusive Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The aims of this study were: i) to assess fragility indices (FIs) of individual randomized controlled trials (RCTs) that compared paclitaxel-based drug-coated balloons (DCBs) or drug-eluting stents (DESs) versus standard endovascular devices, and ii) to meta-analyze mid-term and long-term safety and efficacy outcomes from available RCT data while also estimating the FI of pooled results. METHODS: This systematic review has been registered in the PROSPERO public database (CRD42022304326 http://www.crd.york.ac.uk/PROSPERO). A query of PubMed (Medline), EMBASE (Excerpta Medical Database), Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) databases was performed to identify eligible RCTs. Rates of primary patency (PP) and target lesion revascularization (TLR) were assessed as efficacy outcomes, while lower limb amputation (LLA) consisting of major amputation that is. below or above the knee and all-cause mortality were estimated as safety outcomes. All outcomes were pooled with a random effects model to account for any clinical and study design heterogeneity. The analyses were performed by dividing the RCTs according to their maximal follow-up length (mid-term was defined as results up to 2-3 years, while long-term was defined as results up to 4-5 years). For each individual outcome, the FI and reverse fragility index (RFI) were calculated according to whether the outcome results were statistically significant or not, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ), which are the FI or RFI divided by the sample size, were also calculated. RESULTS: A total of 2,337 patients were included in the systematic review and meta-analysis. There were 2 RCTs examining DES devices and 14 RCTs evaluating different DCBs. For efficacy outcomes, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and reduced the TLR rate at mid-term, with a calculated pooled risk ratio (RR) of 1.66 for patency (95% CI, 1.55-1.86; P < 0.001), with a corresponding number needed-to-treat (NNT) of 3 patients (95% CI, 2.9-3.8) and RR of 0.44 for TLR (95% CI, 0.35-0.54; P = 0.027), respectively. Similarly, there was evidence that paclitaxel-based endovascular therapy both increased PP and decreased TLR rates at long-term, with calculated pooled RR values of 1.73 (95% CI, 1.12-2.61; P = 0.004) and 0.53 (95% CI, 0.45-0.62; P = 0.82), respectively. For safety outcomes, there was evidence that paclitaxel-based endovascular therapy increased all-cause mortality at mid-term, with a calculated pooled RR of 2.05 (95% CI, 1.21-3.24). However, there was no difference between treatment arms in LLA at mid-term (95% CI, 0.1-2.7; P = 0.68). Similarly, neither all-cause mortality nor LLA at long-term differed between treatment arms, with a calculated pooled RR of 0.66, 1.02 (95% CI, 0.31-3.42) and 1.02 (95% CI, 0.30-5.21; P = 0.22), respectively. The pooled estimates of PP at mid-term were robust (FI = 28 and FQ = 1.9%) as were pooled rates of TLR (FI = 18 and FQ = 0.9%). However, when safety outcomes were analyzed, the robustness of the meta-analysis decreased significantly. In fact, the relationship between the use of paclitaxel-coated devices and all-cause mortality at mid-term showed very low robustness (FI = 4 and FQ = 0.2%). At 5 years, only the benefit of paclitaxel-based devices to reduce TLR remained robust, with an FI of 32 and an FQ of 3.1%. CONCLUSIONS: The data supporting clinical efficacy endpoints of RCTs that examined paclitaxel-based devices in the treatment of femoral-popliteal arterial occlusive disease were robust; however, the pooled safety endpoints were highly fragile and prone to bias due to loss of patient follow-up in the original studies. These findings should be considered in the ongoing debate concerning the safety of paclitaxel-based devices.

A Multinational Survey Investigating the Unmet Needs and Patient Perspectives Concerning Proton Pump Inhibitors in Systemic Sclerosis.

OBJECTIVE: Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux disease (GERD) in Systemic Sclerosis (SSc). However, not all patients adequately respond to the treatment, and there are frequent concerns about the safety of long-term use of PPIs. Our aim was to identify the main problems/complaints of SSc patients on PPIs, as well as understand their unmet needs. METHODS: SSc patients treated with PPIs were invited through international patient associations and social media to participate in an online survey. RESULTS: We gathered 301 valid responses from 14 countries (United Kingdom 19.3% and United States 70.4%). Multiple PPIs use (two: 30% and three: 21% in series) was common. The majority (89%) reported improvement in gastrointestinal symptoms from receiving PPIs. Side effects attributed to receiving PPIs were uncommon (19%); however, most (79%) were potentially concerned. Around half (58%) had received lifestyle information, and most (85%) had searched online for information about PPIs. Only in the minority (12%) had a surgical approach been discussed; however, half (46%) indicated that they would be willing to undergo surgery to resolve their GERD symptoms but had important concerns. CONCLUSION: Despite the frequent use of PPIs in patients with SSc, there is significant heterogeneity in prescription, and combination therapy (PPIs plus other medication for acid reflux) is not uncommon (approximately 40%). Patients have significant concerns about PPIs side effects. Education about PPIs is often neglected, and patients very frequently use online sources to obtain information on drug treatment. A surgical approach is infrequently discussed, and patients fear this potential therapeutic approach.

Biomarkers in Systemic Sclerosis: An Overview.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor ß (TGF-ß) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

Pulmonary Sarcoidosis and Immune Dysregulation: A Pilot Study on Possible Correlation.

BACKGROUND: Sarcoidosis is a systemic inflammatory disease characterized by an altered inflammatory response. OBJECTIVE: The aim of this study was to evaluate whether immune system alterations detected by lymphocyte typing in peripheral blood correlate with the severity of sarcoidosis, calculated according to two separate severity scores proposed by Wasfi in 2006 and Hamzeh in 2010. MATERIALS AND METHODS: Eighty-one patients were recruited, and clinical data and laboratory tests at the time of diagnosis were obtained in order to assess the severity index score and investigate any statistically significant correlation with the cytofluorimetry data. RESULTS: Our data demonstrated that none of the two scores show an association with the level of total lymphocytes or lymphocyte subclasses. LIMITATIONS: First of all, the sample taken into consideration is small. The assessment was performed only at disease onset and not during the disease. Furthermore, the severity scores do not take into account disease activity (measured by PET/CT or gallium scintigraphy). CONCLUSIONS: Lymphocyte subpopulation values at the time of diagnosis do not appear to correlate with disease severity at onset.

A Review: The Potential Involvement of Growth Arrest-Specific 6 and Its Receptors in the Pathogenesis of Lung Damage and in Coronavirus Disease 2019.

The tyrosine kinase receptors of the TAM family-Tyro3, Axl and Mer-and their main ligand Gas6 (growth arrest-specific 6) have been implicated in several human diseases, having a particularly important role in the regulation of innate immunity and inflammatory response. The Gas6/TAM system is involved in the recognition of apoptotic debris by immune cells and this mechanism has been exploited by viruses for cell entry and infection. Coronavirus disease 2019 (COVID-19) is a multi-systemic disease, but the lungs are particularly affected during the acute phase and some patients may suffer persistent lung damage. Among the manifestations of the disease, fibrotic abnormalities have been observed among the survivors of COVID-19. The mechanisms of COVID-related fibrosis remain elusive, even though some parallels may be drawn with other fibrotic diseases, such as idiopathic pulmonary fibrosis. Due to the still limited number of scientific studies addressing this question, in this review we aimed to integrate the current knowledge of the Gas6/TAM axis with the pathophysiological mechanisms underlying COVID-19, with emphasis on the development of a fibrotic phenotype.

Theory and Practice of Glucocorticoids in COVID-19: Getting to the Heart of the Matter-A Critical Review and Viewpoints.

Prolonged, low-dose glucocorticoids (GCs) have shown the highest efficacy among pharmacological and non-pharmacological treatments for COVID-19. Despite the World Health Organization's recommendation against their use at the beginning of the pandemic, GCs at a dose equivalent to dexamethasone 6 mg/day for 10 days are now indicated in all COVID-19 cases who require respiratory support. However, the efficacy of the intervention depends on the timing of initiation, the dose, and other individual factors. Indeed, patients treated with similar GC protocols often experience different outcomes, which do not always correlate with the presence of comorbidities or with the severity of respiratory involvement at baseline. This prompted us to critically review the literature on the rationale, pharmacological principles, and clinical evidence that should guide GC treatment. Based on these data, the best treatment protocol probably involves an initial bolus dose to saturate the glucocorticoid receptors, followed by a continuous infusion to maintain constant plasma levels, and eventually a slow tapering to interruption. Methylprednisolone has shown the highest efficacy among different GC molecules, most likely thanks to its higher ability to penetrate the lung. Decreased tissue sensitivity to glucocorticoids is thought to be the main mechanism accounting for the lower response to the treatment in some individuals. We do not have a readily available test to identify GC resistance; therefore, to address inter-individual variability, future research should aim at investigating clinical, physiological, and laboratory markers to guide a personalized GC treatment approach.

Microvascular Alteration in COVID-19 Documented by Nailfold Capillaroscopy.

COVID-19 is a multisystemic disease that mainly affects and causes dysregulation of the endothelium, causing systemic manifestations. A nailfold video capillaroscopy is a safe, easy, and noninvasive method to evaluate microcirculation alteration. In this review, we analyzed the literature available to date regarding the object of nailfold video capillaroscopy (NVC) use in patients with a SARS-CoV-2 infection, both in the acute phase and after discharge. The scientific evidence pointed out the main alterations in capillary circulation shown by NVC, so reviewing the findings of each article allowed us to define and analyze the future prospects and needs for possibly including NVC within the management of patients with COVID-19, both during and after the acute phase.

Nintedanib in Idiopathic Pulmonary Fibrosis: Tolerability and Safety in a Real Life Experience in a Single Centre in Patients also Treated with Oral Anticoagulant Therapy.

Idiopathic pulmonary fibrosis (IPF) is a rare and severe disease with a median survival of ~3 years. Nintedanib (NTD) has been shown to be useful in controlling interstitial lung disease (ILD) in IPF. Here we describe the experience of NTD use in IPF in a real-life setting. Objective. Our objective was to examine the safety profile and efficacy of nintedanib even in subjects treated with anticoagulants. Clinical data of patients with IPF treated with NTD at our center were retrospectively evaluated at baseline and at 6 and 12 months after the introduction of NTD. The following parameters were recorded: IPF clinical features, NTD tolerability, and pulmonary function tests (PFT) (i.e., Forced Vital Capacity (FVC) and carbon monoxide diffusing capacity (DLCO)). In total, 56 IPF patients (34% female and 66% male, mean onset age: 71 ± 11 years, mean age at baseline: 74 ± 9 years) treated with NTD were identified. At enrollment, HRCT showed an UIP pattern in 45 (80%) and a NSIP in 11 (20%) patients. For FVC and FEV1 we found no significant change between baseline and 6 months, but for DLCO we observed a decrease (p = 0.012). We identified a significant variation between baseline and 12 months for FEV1 (p = 0.039) and for DLCO (p = 0.018). No significant variation was observed for FVC. In the cohort, 18 (32%) individuals suspended NTD and 10 (18%) reduced the dosage. Among individuals that suspended the dosage, 14 (78%) had gastrointestinal (GI) collateral effects (i.e., diarrhea being the most common complaint (67%), followed by nausea/vomiting (17%) and weight loss (6%). Bleeding episodes have also not been reported in patients taking anticoagulant therapy. (61%). One patient died within the first 6 months and two subjects died within the first 12 months. In a real-life clinical scenario, NTD may stabilize the FVC values in IPF patients. However, GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in IPF patients. This study confirms the safety of NTD, even in patients treated with anticoagulant drugs.

Special Issue "Rheumatic Diseases: Pathophysiology, Targeted Therapy, Focus on Vascular and Pulmonary Manifestations 2022".

This Special Issue, titled "Rheumatic Diseases: Pathophysiology, Targeted Therapy, Focus on Vascular and Pulmonary Manifestations", aims to demonstrate recent and new advances and future trends in the field of rheumatic diseases [...].