Clinical and structural damage outcomes in axial spondyloarthritis patients receiving NSAIDs or advanced therapies: a description of a real-life cohort.

Introduction: This study aims to describe the clinical characteristics, disease activity, and structural damage in patients with axial spondyloarthritis (axSpA) who receive chronic treatment with nonsteroideal anti-inflammatory drugs (NSAIDs) or advanced therapies in a clinical setting. Methods: Cross-sectional study on axSpA patients consecutively recruited from the outpatient clinic of a tertiary hospital. We collected data on clinical and demographic characteristics, as well as treatment patterns involving NSAIDs and advanced therapies. Structural damage was assessed using mSASSS. Results: Overall, data from 193 axSpA patients (83% ankylosing spondylitis) were gathered, with a mean disease duration of 21.4 years. Of these, 85 patients (44%) were exclusively taking NSAIDs, while 108 (56%) were receiving advanced therapies, with TNF inhibitors being the predominant choice (93 out of 108, 86.1%). Among patients using NSAIDs, 64.7% followed an on-demand dosing regimen, while only 17.6% used full doses. Disease activity was low, with a mean BASDAI of 3.1 and a mean ASDAS-CRP of 1.8. In comparison to patients under chronic NSAID treatment, those taking advanced therapies were primarily male (69.4% versus 51.8%, p = 0.025) and significantly younger (mean age of 49 versus 53.9 years, p = 0.033). Additionally, patients on advanced therapies exhibited lower ASDAS-CRP (p = 0.046), although CRP serum levels and BASDAI scores did not differ between the two groups. In the multivariable analysis, therapy (NSAID versus biological treatment) was not independently associated with ASDAS-CRP, BASDAI or mSASSS. Conclusion: This cross-sectional analysis of a real-world cohort of axSpA patients shows positive clinical and radiological outcomes for both NSAIDs and advanced therapies.

Clinical characteristics and outcomes of community-acquired pneumonia in solid organ transplant recipients.

BACKGROUND: Pneumonia is a frequent complication of solid organ transplantation that adversely impacts both graft and recipient survival. There is a paucity of data on community-acquired pneumonia (CAP) in transplant recipients, particularly the long term outcomes. We conducted a study to compare the clinical characteristics and outcomes of pneumonia in solid organ transplant (SOT) recipients to those in non-transplant (NT) recipients. MATERIAL AND METHODS: Clinical characteristics were abstracted from electronic medical records. Outcomes included time to hospital discharge, short and long-term mortality. Inverse-propensity score weights were assigned to account for between-group differences. Adjusted analysis included a weighted logistic regression. Results were reported as odds ratios with a corresponding 95 % confidence interval (CI). RESULTS: A total of 7449 patients were admitted with CAP. Patients were divided into two groups: SOT recipients 42 (0.56 %) and NT recipients 7396 (99.2 %). SOT recipients were younger, more commonly males, with higher prevalence of comorbidities. After accounting for inverse-propensity score weighting, the odds of mortality were higher in SOT recipients in hospital, at 30 days and at 1 year. The magnitude of increase in mortality for SOT recipients was greatest at 1 year with 1.41 (95 % CI: 1.38-1.44) times higher odds. CONCLUSION: In patients with CAP, SOT recipients are younger, more commonly male and have more co-morbidities compared with NT recipients. They also have higher 1 year mortality after adjustment. Clinicians must be vigilant toward the pronounced long-term mortality risk among these patients and ensure continued follow-up care for them.

Different clinical characteristics and outcomes of adult hospitalized SARS-CoV-2 pneumonia patients complicated by cardiovascular events during the first, delta and omicron waves of COVID-19.

Background: The effects of SARS-CoV-2 have varied between significant waves of hospitalization. Research question: Are cardiovascular complications different among the first, delta and omicron waves of hospitalized COVID-19 pneumonia patients? Study design and methods: This was a multi-centre retrospective study of patients hospitalized with SARS-CoV-2 pneumonia: 632 were hospitalized during the first wave (March-July 2020), 1013 during the delta wave (September 2020-March 2021), and 323 during the omicron wave (January 2022-July 2022). Patients were stratified by wave and occurrence of cardiovascular events. Results: Among all hospitalized patients with cardiovascular events, patients in the omicron wave were younger (62.4 ± 14 years) than patients in the first wave (67.4 ± 7.8 years) and the delta wave (66.9 ± 12.6 years) and had a higher proportion of non-Hispanic White people than in the first wave (78.6% vs. 61.7%). For COVID-19 patients who suffered from cardiovascular events, the omicron wave patients had significantly higher neutrophil/lymphocyte ratio, white blood cell and platelet counts when compared to the first wave. Omicron wave patients had significantly lower albumin and B-type natriuretic peptide levels (only 5.8% of the first wave and 14.6% of the delta wave) when compared to either the first wave or delta wave patients. In COVID-19 patients who suffered cardiovascular events during hospitalization, mortality rate in the omicron wave (26.8%) was significantly lower than the first wave (48.3%), time to mortality for non-survivors of COVID-19 patients who suffered cardiovascular events was significantly longer in the omicron wave (median 16 days) than in the first wave (median 10 days). Conclusions: Younger and white patients were affected with cardiovascular complications more often by the omicron variant. Despite higher neutrophil/lymphocyte ratio and WBC counts, the omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves.

Challenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.

Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.

Neutrophilic Activity Biomarkers (Plasma Neutrophil Extracellular Traps and Calprotectin) in Established Patients with Rheumatoid Arthritis Receiving Biological or JAK Inhibitors: A Clinical and Ultrasonographic Study.

INTRODUCTION: This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity. METHODS: Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3 months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves. RESULTS: One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P < 0.001, Clinical Disease Activity Index [CDAI] rho = 0.30; P < 0.001) and ultrasound parameters (rho > 0.50; P < 0.001). Notably, this correlation was stronger than that observed with acute phase reactants. CONCLUSION: While NET formation induced by neutrophils may play a role in RA pathogenesis, our study raises questions about the utility of NET remnants in peripheral circulation as a biomarker for inflammatory activity. In contrast, this study strongly supports the usefulness of calprotectin as a biomarker of inflammatory activity in patients with RA.

Synovial 5-Lipoxygenase-Derived Oxylipins Define a Lympho-Myeloid-Enriched Synovium.

OBJECTIVE: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histologic patterns. METHODS: Patients with established rheumatoid or psoriatic arthritis with active disease despite treatment were recruited, and paired synovial tissue (ST) and plasma were collected. Oxylipins were determined by liquid chromatography with tandem mass spectrometry and were classified into groups according to their PUFA precursor and enzyme. The expression of CD20, CD68, CD3, and CD138 was obtained to describe synovial histology. Cell-specific expression of oxylipin-related genes was identified by examining available synovial single-cell RNA sequencing data. RESULTS: We included a total of 32 ST and 26 paired-plasma samples. A total of 71 oxylipins were identified in ST, but only 24 were identified in plasma. Only levels of 9,10-dihydroxyoctadecenoic acid and tetranor-Prostaglandin FM had a significant positive correlation between plasma and ST. Several oxylipins and oxylipin-related genes were differentially expressed among synovial phenotypes. Specifically, several 5-lipoxygenase (LOX)-derived oxylipins were statistically elevated in the lympho-myeloid phenotype and associated with B cell expression in rheumatoid arthritis samples. CONCLUSION: The lack of correlation between ST and plasma oxylipins suggests that ST lipid profiling better characterizes active pathways in treated joints. Synovial 5-LOX-derived oxylipins were highly expressed in lympho-myeloid-enriched synovium. Combination therapy with 5-LOX inhibitors to improve refractory inflammation may be needed in patients with this histologic group.

Definition, Epidemiology, and Pathogenesis of Severe Community-Acquired Pneumonia.

The clinical presentation of community-acquired pneumonia (CAP) can vary widely among patients. While many individuals with mild symptoms can be managed as outpatients with excellent outcomes, there is a distinct subgroup of patients who present with severe CAP. In these cases, the mortality rate can reach approximately 25% within 30 days and even up to 50% within a year. It is crucial to focus attention on these patients who are at higher risk. Among the various definitions of severe CAP found in the literature, one commonly used criterion is the requirement for admission to intensive care unit. Notable epidemiological characteristics of these patients include the impact of acute cardiovascular diseases on clinical outcomes and the enduring, independent effect of pneumonia on long-term outcomes. Factors such as pathogen virulence, the presence of comorbidities, and the host response are important contributors to the pathogenesis of severe CAP. In these patients, the host response may be dysregulated and compartmentalized. Gaining a better understanding of the epidemiology and pathogenesis of severe CAP will provide a foundation for the development of new therapies for this condition. This manuscript aims to review the definition, epidemiology, and pathogenesis of severe CAP, shedding light on important aspects that can aid in the improvement of patient care and outcomes.

Influenza and Viral Pneumonia.

Influenza and other respiratory viruses are commonly identified in patients with community-acquired pneumonia, hospital-acquired pneumonia, and in immunocompromised patients with pneumonia. Clinically, it is difficult to differentiate viral from bacterial pneumonia. Similarly, the radiological findings of viral infection are in general nonspecific. The advent of polymerase chain reaction testing has enormously facilitated the identification of respiratory viruses, which has important implications for infection control measures and treatment. Currently, treatment options for patients with viral infection are limited but there is ongoing research on the development and clinical testing of new treatment regimens and strategies.

Synovial tissue features associated with poor prognosis in inflammatory arthritis.

BACKGROUND: Inflammatory arthritis encompasses a group of immune-mediated diseases characterized by chronic joint inflammation. Despite having pathogenic mechanisms in common, the prognosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and undifferentiated arthritis (UA) could be different regarding progression to chronic, to erosive, or to self-limited disease. Our aim was to evaluate the potential association of synovial tissue (ST) inflammatory cell infiltrate, the presence of ectopic lymphoid neogenesis (LN +) structures, and poor prognosis factors (PPF) in patients with RA, PsA, and UA. METHODS: We conducted a retrospective study including patients with active arthritis (RA, PsA, UA) who had ST obtained by rheumatological arthroscopy or ultrasound-guided biopsy. Clinical, demographic, and immunohistochemical data of the synovium was evaluated. Patients with biological therapy at the time of synovial biopsy were excluded. PPF in patients with RA and UA were defined by the presence of anti-cyclic citrullinated peptide antibodies and/or rheumatoid factor, development of bone erosions, or requirement of biological therapy during the follow-up. PPF in patients with PsA were defined as the presence of high levels of acute-phase reactants (ESR/CRP), dactylitis or nail involvement at the time of biopsy, development of bone erosion, or requirement of biological therapy during the follow-up. RESULTS: A total of 88 patients were included: 26 RA, 33 PsA, and 29 UA. All patients were followed up for 5 years after the biopsy. Fourteen (53.84%) RA patients had PPF, and 17 (65.38%) had LN + . LN + was associated with PPF (p 0.038) and biologic therapy initiation (p 0.018). A total of 14 (43.75%) PsA patients had PPF. CD15 infiltrate (410.68 [SD 477.63] cells/mm2) was associated with PPF (p 0.008) in PsA patients. Sixteen (55.17%) patients with UA had PPF, and 13 (44.82%) had LN + . In this group, synovial CD68 + macrophages cells density was negatively correlated with DAS28-CRP (r = - 0.346, p 0.042). CONCLUSIONS: The presence of LN + and higher CD15 + polymorphonuclear cells infiltrate was associated with PPF in RA and PsA, respectively. No associations were found for UA. These findings suggest a great heterogeneity of the ST features and its pathogenic implications in the subtypes of inflammatory arthritis.

Corrigendum: The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2023.1191782.].

Improved spatial speckle contrast model for tissue blood flow imaging: effects of spatial correlation among neighboring camera pixels.

Significance: Speckle contrast analysis is the basis of laser speckle imaging (LSI), a simple, inexpensive, noninvasive technique used in various fields of medicine and engineering. A common application of LSI is the measurement of tissue blood flow. Accurate measurement of speckle contrast is essential to correctly measure blood flow. Variables, such as speckle grain size and camera pixel size, affect the speckle pattern and thus the speckle contrast. Aim: We studied the effects of spatial correlation among adjacent camera pixels on the resulting speckle contrast values. Approach: We derived a model that accounts for the potential correlation of intensity values in the common experimental situation where the speckle grain size is larger than the camera pixel size. In vitro phantom experiments were performed to test the model. Results: Our spatial correlation model predicts that speckle contrast first increases, then decreases as the speckle grain size increases relative to the pixel size. This decreasing trend opposes what is observed with a standard speckle contrast model that does not consider spatial correlation. Experimental data are in good agreement with the predictions of our spatial correlation model. Conclusions: We present a spatial correlation model that provides a more accurate measurement of speckle contrast, which should lead to improved accuracy in tissue blood flow measurements. The associated correlation factors only need to be calculated once, and open-source software is provided to assist with the calculation.

Dual targeted therapy in patients with psoriatic arthritis and spondyloarthritis: a real-world multicenter experience from Spain.

Dual targeted therapy (DTT) has emerged as a promising approach in patients with refractory spondyloarthritis (SpA) or psoriatic arthritis (PsA) and extra-musculoskeletal manifestations of both diseases, but its effectiveness/safety ratio still remains unclear. This is a retrospective, real-world multicenter study in refractory SpA and PsA patients with simultaneous use of two biological or synthetic targeted agents. Effectiveness was assessed using Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) and Disease Activity in Psoriatic Arthritis (DAPSA) Score. We identified 39 different DTT combinations in 36 patients (22 SpA; 14 PsA), 25 of them with concomitant inflammatory bowel disease. The most commonly used combinations were TNF inhibitor plus antagonist of the IL12/23 pathway, followed by TNF inhibitor plus IL-17 antagonist. During a median exposure of 14.86 months (IQR 8-20.2), DTT retention rate was 69.4% (n=25/36; 19 SpA, 6 PsA). Major clinical improvement (change in ASDAS-CRP > 2 or improvement > 85% in DAPSA) was achieved in 69.4% of patients (n=25/36 therapeutical combinations; 17/21 SpA, 8/15 PsA), with a 58.3% (n=21/36 combinations; 15/20 SpA, 6/13 PsA) low-activity/remission rate. Of the patients who were receiving glucocorticoids, 55% managed to withdraw them during follow-up. Interestingly, only four serious adverse events in three patients were observed, leading to DTT discontinuation.

Epidemiology of Pneumococcal Pneumonia in Louisville, Kentucky, and Its Estimated Burden of Disease in the United States.

Streptococcus pneumoniae remains a primary pathogen in hospitalized patients with community-acquired pneumonia (CAP). The objective of this study was to define the epidemiology of pneumococcal pneumonia in Louisville, Kentucky, and to estimate the burden of pneumococcal pneumonia in the United States (US). This study was nested in a prospective population-based cohort study of all adult residents in Louisville, Kentucky, who were hospitalized with CAP from 1 June 2014 to 31 May 2016. In hospitalized patients with CAP, urinary antigen detection of 24 S. pneumoniae serotypes (UAD-24) was performed. The annual population-based pneumococcal pneumonia incidence was calculated. The distribution of S. pneumoniae serotypes was characterized. Ecological associations between pneumococcal pneumonia and income level, race, and age were defined. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Among the 5402 CAP patients with a UAD-24 test performed, 708 (13%) patients had pneumococcal pneumonia. The annual cumulative incidence was 93 pneumococcal pneumonia hospitalizations per 100,000 adults (95% CI = 91-95), corresponding to an estimated 226,696 annual pneumococcal pneumonia hospitalizations in the US. The most frequent serotypes were 19A (12%), 3 (11%), and 22F (11%). Clusters of cases were found in areas with low incomes and a higher proportion of Black or African American population. Pneumococcal pneumonia mortality was 3.7% during hospitalization, 8.2% at 30 days, 17.6% at 6 months, and 25.4% at 1 year after hospitalization. The burden of pneumococcal pneumonia in the US remains significant, with an estimate of more than 225,000 adults hospitalized annually, and approximately 1 out of 4 hospitalized adult patients dies within 1 year after hospitalization.

Community-Acquired Pneumonia in the Immunocompromised Host: Epidemiology and Outcomes.

Background: The epidemiology and outcomes of community-acquired pneumonia (CAP) in immunocompromised hosts (ICHs) are not well defined. The objective of this study was to define the epidemiology and outcomes of CAP in ICHs as compared with non-ICHs. Methods: This ancillary study included a prospective cohort of hospitalized adult Louisville residents with CAP from 1 June 2014 to 31 May 2016. An ICH was defined per the criteria of the Centers for Disease Control and Prevention. Geospatial epidemiology explored associations between ICHs hospitalized with CAP and income level, race, and age. Mortality for ICHs and non-ICHs was evaluated during hospitalization and 30 days, 6 months, and 1 year after hospitalization. Results: A total of 761 (10%) ICHs were identified among 7449 patients hospitalized with CAP. The most common immunocompromising medical conditions or treatments were advanced-stage cancer (53%), cancer chemotherapy (23%), and corticosteroid use (20%). Clusters of ICHs hospitalized with CAP were found in areas associated with low-income and Black or African American populations. Mortality by time point for ICHs vs non-ICHs was as follows: hospitalization, 9% vs 5%; 30 days, 24% vs 11%; 6 months, 44% vs 21%; and 1 year, 53% vs 27%, respectively. Conclusions: Approximately 1 in 10 hospitalized patients with CAP is immunocompromised, with advanced-stage cancer being the most frequent immunocompromising condition, as seen in half of all patients who are immunocompromised. Risk for hospitalization may be influenced by socioeconomic disparities and/or race. ICHs have a 2-fold increase in mortality as compared with non-ICHs.

The paradigm of IL-23-independent production of IL-17F and IL-17A and their role in chronic inflammatory diseases.

Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.

Calprotectin in Patients with Rheumatic Immunomediated Adverse Effects Induced by Checkpoints Inhibitors.

BACKGROUND: this is an exploratory study to evaluate calprotectin serum levels in patients with rheumatic immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) treatment. METHODS: this is a retrospective observational study including patients with irAEs rheumatic syndromes. We compared the calprotectin levels to those in a control group of patients with RA and with a control group of healthy individuals. Additionally, we included a control group of patients treated with ICI but without irAEs to check calprotectin levels. We also analysed the performance of calprotectin for the identification of active rheumatic disease using receiver operating characteristic curves (ROC). RESULTS: 18 patients with rheumatic irAEs were compared to a control group of 128 RA patients and another group of 29 healthy donors. The mean calprotectin level in the irAE group was 5.15 µg/mL, which was higher than the levels in both the RA group (3.19 µg/mL) and the healthy group (3.81 µg/mL) (cut-off 2 µg/mL). Additionally, 8 oncology patients without irAEs were included. In this group, calprotectin levels were similar to those of the healthy controls. In patients with active inflammation, the calprotectin levels in the irAE group were significantly higher (8.43 µg/mL) compared to the RA group (3.94 µg/mL). ROC curve analysis showed that calprotectin had a very good discriminatory capacity to identify inflammatory activity in patients with rheumatic irAEs (AUC of 0.864). CONCLUSIONS: the results suggest that calprotectin may serve as a marker of inflammatory activity in patients with rheumatic irAEs induced by treatment with ICIs.