Sarcoidosis Patients Research Articles

Characteristics and Outcomes of Hospitalized Patients With Heart Failure and Sarcoidosis: A Propensity-Matched Analysis of the Nationwide Readmissions Database 2010-2019

BackgroundSarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. MethodsThe US Nationwide Readmission Database was queried from 2010 to 2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, 9th and 10th Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. ResultsWe identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs 1.4%, P < .0001), ventricular tachycardia (6.5% vs 1.3%, P < .0001), ventricular fibrillation (0.4% vs 0.1%, P < .0001) and atrial fibrillation (22.1% vs 7.5%, P < .0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, P < .0001), had higher length of hospital stay (5 vs 4 days, P < .0001), adjusted healthcare-associated costs ($9,667.0 vs $9,087.1, P < .0001) and mortality rates on readmission (5.1% vs 3.8%, P < .0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI, and liver disease. ConclusionSwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study

BackgroundClinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AimTo determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. MethodsTwo large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. ResultsBetween 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. ConclusionsHigh–risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

БИОЛОГИЧЕСКИЕ МАРКЕРЫ ФИБРОЗООБРАЗОВАНИЯ У БОЛЬНЫХ САРКОИДОЗОМ ЛЕГКИХ

Introduction. Sarcoidosis-associated pulmonary fibrosis still lacks biomarkers to predict progression. Whole-genome association studies and other genetic research over the past few years have identified several single nucleotide polymorphisms that are associated with an increased risk of developing pulmonary fi brosis. In sarcoidosis, relatively reliable predictors of the disease activity include serum angiotensin-converting enzyme, soluble interleukin-2 receptor (sIL-2R) and chitotriosidase. Levels of inetrleukin-5 and, possibly, interleukin-7 were found to be elevated in patients with a fibrotic phenotype. Aim. In the present study, we sought to find the relationship between serum non- coding RNA- microRNA expression in patients with pulmonary sarcoidosis and the likelihood of pulmonary fibrosis developing in these patients. Materials and Methods. A total of 52 research subjects (sarcoidosis patients with/without fibrosis and healthy subjects) were included in the study. RNA samples from two groups of sarcoidosis patients (with and without fibrosis) and the control group were analyzed using the PCR Array. TaqMan QRT-PCR Assay was used for data verification. Results and Discussion. A significant decrease in the lung diffusion capacity was detected in 12 of 15 patients with chest-CT fibrosis signs. Lung diffusion capacity was normal in 17 patients without any fibrosis signs. There was a significant negative correlation among miR-15a, miR-150, and the level of lung diffusion capacity. Сonclusions. A set of non-coding RNA- microRNAs, i. e., miR-15a, miR-22, miR-106b, miR-107, and miR-150, was identified that can be further used as diagnostic markers for sarcoidosis fibrosis.

Comparison of organ involvement clusters in Black and White American sarcoidosis patients from a prospectively collected patient registry

BackgroundDue to the heterogeneity of sarcoidosis, there is a need to define clinical phenotypes to allow for tailoring of clinical care and identification of more homogenous populations to facilitate research. MethodsWe utilized data from a prospectively collected registry of sarcoidosis patients seen at a single quaternary referral center between January 2019 and February 2021. We used multiple correspondence analysis (MCA) and k-means clustering to investigate if the clusters previously identified in the GenPhenReSa study were reproducible in a US population. We also investigated if these clusters were stable when the population was stratified by race. ResultsWe replicated 3 of the 5 clusters seen in the GenPhenReSa study in our cohort. We likewise identified similar clusters between White and Black patients with sarcoidosis. Differences in organ manifestations associations between White and Black patients were seen primarily in relation to cardiac, neurologic, and ocular involvement. ConclusionsThe organ clusters of liver-spleen, isolated pulmonary, and musculoskeletal-skin were reproducible in a US cohort, and in both Black and White patients.

Diagnostic yield of the Kveim test in sarcoidosis patients.

Sarcoidosis is a granulomatous disorder of unknown etiology characterized by the existence of non-caseating granulomatous inflammation. Diagnosis can be challenging due to the presence of comprehensive clinical, laboratory, and radiologic manifestations. We have evaluated the diagnostic yield of the Kveim test and compared this test with the other conventional laboratory modalities. Our aim was to reach the highest level of diagnostic confidence acknowledging the absolute uncertainty in diagnosis with the current diagnostic enterprises. Medical records of 300 sarcoidosis patients were reviewed. Patients were classified into two categories as the conventional laboratory and the Kveim test group to compare the diagnostic yield. Sensitivity of the Kveim test was 76.4% while the conventional laboratory tests provided a 64% diagnostic yield. The conventional tests had a low diagnostic rate in the early disease stages. Kveim test revealed a high yield diagnosis for all stages of sarcoidosis. Integrated assessment of the two modalities reached a 96.8% sensitivity and a 94,6% specificity. Conventional laboratory modalities were useful for the assessment of disease activity and identification of organ involvement. Kveim test revealed a significant diagnostic yield for all stages of sarcoidosis. The lowest output was achieved in stage IV patients due to the waning of active granulomatous inflammation. The highest diagnostic sensitivity was obtained by an integrated analysis of the conventional laboratory and the Kveim test results for all aspects of sarcoidosis.

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

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. 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. 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. 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. 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.

Immunological Similarities and Differences between Post-COVID-19 Lung Sequelae and Idiopathic Pulmonary Fibrosis.

Pulmonary fibrosis is an irreversible condition that may be caused by known (including viral triggers such as SARS-CoV-2) and unknown insults. The latter group includes idiopathic pulmonary fibrosis (IPF), which is a chronic, progressive fibrosing interstitial pneumonia of unknown cause. The longer the insult acts on lung tissue, the lower the probability of a complete resolution of the damage. An emerging clinical entity post-COVID-19 is pulmonary fibrosis (PCPF), which shares many pathological, clinical, and immunological features with IPF. The fibrotic response in both diseases-IPF and PCPF-is orchestrated in part by the immune system. An important role regarding the inhibitory or stimulatory effects on immune responses is exerted by the immune checkpoints (ICs). The aim of the present study was to analyse the similarities and differences between CD4+, CD8+, and NK cells in the peripheral blood of patients affected by fibrotic disease, IPF, and PCPF compared with sarcoidosis patients and healthy controls. The second aim was to evaluate the expression and co-expression of PD-1 and TIGIT on CD4, CD8, and NK cells from our patient cohort. One hundred and fifteen patients affected by IPF, PCPF, and sarcoidosis at the rare pulmonary disease centre of the University of Siena were enrolled. Forty-eight patients had an IPF diagnosis, 55 had PCPF, and 12 had sarcoidosis. Further, ten healthy controls were enrolled. PCPF patients were included between 6 and 9 months following hospital discharge for COVID-19. The peripheral blood samples were collected, and through flow cytometric analysis, we analysed the expression of CD4, CD8, NK cells, PD-1, and TIGIT. The results show a greater depletion of CD4 and NK cells in IPF patients compared to other groups (p = 0.003), in contrast with CD8 cells (p < 001). Correlation analysis demonstrated an indirect correlation between CD4 and CD8 cells in IPF and sarcoidosis patients (p < 0.001 = -0.87 and p = 0.042; r = -0.6, respectively). Conversely, PCPF patients revealed a direct correlation between CD4 and CD8 cells (p < 0.001; r = 0.90) accentuating an immune response restoration. The expression of PD-1 and TIGIT was abundant on T and NK cell subsets of the two lung fibrotic groups, IPF and PCPF. Analogously, the co-expression of PD-1 and TIGIT on the surfaces of CD4 and CD8 were increased in such diseases. Conclusions: Our study shines a spotlight on the immune responses involved in the development of pulmonary fibrosis, idiopathic and secondary to SARS-CoV-2 infection. We observed a significant imbalance not only in CD4, CD8, and NK blood percentages in IPF and PCPF patients but also in their functional phenotypes evaluated through the expression of ICs.

Characteristics and clinical outcomes of patients with Sarcoidosis admitted for ST-elevation myocardial infarction in the United States: A propensity matched analysis from the National Inpatient Sample

IntroductionSarcoidosis is a systemic inflammatory disorder characterised by non-caseating granulomas. Cardiac sarcoidosis (CS) normally causes conduction abnormalities, ventricular arrhythmias, and heart failure. Little is known about the characteristics and impact of sarcoidosis in patients admitted with ST-elevation myocardial infarction (STEMI). This study aims to fill this void.Material and methodsUtilising the National Inpatient Sample (NIS) database (2016–2020), individuals with STEMI were identified and categorised based on sarcoidosis presence whilst adjusting for confounders via logistic regression models.ResultsAmong 851,290 STEMI patients, 1215 had sarcoidosis. Before propensity matching, sarcoidosis patients were notably different in demographics and comorbidities compared to non-sarcoidosis patients. After propensity score matching (PSM), sarcoidosis patients were found to have a higher incidence of supraventricular tachycardia (SVT) (2.5% vs. 1.3%, p = 0.024) and acute kidney injury (AKI) (23.3% vs. 20.8%, aOR = 1.269, 95% CI: 1.02–1.58, p = 0.033) but a lower incidence of undergoing coronary artery bypass graft (CABG) (5.5% vs. 8.5%, aOR = 0.663; 95% CI: 0.472–0.931, p = 0.018), while no significant disparities were noted in PCI, cardiogenic shock, mortality, or mean length of stay (LOS).ConclusionsUsing propensity-matched large real-world data of STEMI patients, sarcoidosis was associated with fewer cases of CABG and a greater incidence of AKI and SVT compared to non-sarcoidosis patients.

Peri-Operative Outcomes Associated With the Placement of Implantable Cardioverter-Defibrillators in Patients With Sarcoidosis: A Nationwide Database Analysis.

Rationale Sarcoidosis with cardiac involvement can be associated with serious life-threatening arrhythmias and an increased risk of sudden cardiac death. Implantable cardiac defibrillators (ICDs) have been used for primary and secondary prevention of sudden death in patients with cardiac sarcoidosis (CS).Post-ICD placement complications have been shown to be higher in patients with CS. However, data comparing postoperative ICD complications among sarcoidosis patients with the general population is limited. Here, we evaluated the association of postoperative complications with implantable cardioverter-defibrillators in sarcoidosis. Methods Using the NIS database, we identified cases of adults aged ≥ 18 years undergoing surgical placement of implantable cardioverter-defibrillators between 2010 and 2019. Using ICD-9 and ICD-10 codes, we identified patients with sarcoidosis. In all statistical analyses, we applied weights provided by HCUP to produce results representative of national estimates. We compared categorical and continuous covariates in the baseline characteristics using the chi-square test and analysis of variance, respectively. We employed multivariable logistic and linear regression to compare binomial and continuous outcomes to assess differences in mortality rates. Results We analyzed 114073 patients during the study period. Of these, 1012 (0.9%) had sarcoidosis and were found to be significantly younger and female compared to patients without sarcoidosis (56.4 ±11.5 years vs. 65.6 ± 13.9 years, p <0.001) and (39.4% vs. 28.3%, p<0.001) respectively. Further, patients with sarcoidosis were more likely to be African American (45% vs. 16.3%), have private insurance (45.4% vs. 23.8%), and less likely to have Medicare (34.9% vs. 60.9%). Overall, post-ICD placement complications such as lead complications (4.2% vs. 6.9%, p = 0.03), post-procedure hemorrhage (4.1% vs. 5.5%, p=0.048), and requirement for transfusion (2.3% vs. 4.4%) were less likely in patients with sarcoidosis. Regarding post-ICD placement inpatient mortality, sarcoidosis was not associated with any difference(OR: 0.71, 95% CI 0.18-2.88 p=0.634). Conclusions Placement of implantable cardioverter-defibrillators in patients with sarcoidosis is a safe procedure and is associated with significantly lower rates of lead complications, post-procedure hemorrhage, and requirement for transfusion. This is of great importance as it is known that patients with underlying sarcoidosis are predisposed to developing more cardiac complications.

Quadriceps femoris muscle ultrasound in sarcoidosis: an observational case-control study.

Although loss of muscle mass may be associated with general weakness, intolerance to physical activity and fatigue, it is underestimated and poorly understood in patients with sarcoidosis. To compare the quadriceps femoris muscle (QFM) thickness measured by ultrasonography (US) between the female patients with sarcoidosis and controls, secondly to assess the correlation between the muscle strength, fatigue and QFM thickness. Observational, case-control study. Physical Medicine and Rehabilitation Department of a University Hospital. Thirty-one women with sarcoidosis and 27 healthy volunteers were included in the study. The participants were evaluated for the following outcomes: 1) handgrip strength; 2) QFM thickness measured using US; and 3) sonographic thigh adjustment ratio (STAR). The sarcoidosis group was also evaluated with the 30-second chair stand test (30s-CST) and Fatigue Severity Scale (FSS). The QFM thickness and STAR values of the patients with sarcoidosis were significantly lower than those of the controls (P=0.0001). However, no statistically significant difference was observed between the handgrip strengths of the groups (P=0.581). There was no statistically significant correlation between the STAR values and handgrip strength in the sarcoidosis group; however, there was a significant positive correlation between the STAR values and 30s-CST (r=0.467, P=0.008). Loss of muscle mass is one of the musculoskeletal conditions in patients with sarcoidosis that may be associated with nonspecific symptoms, such as general debility, intolerance to physical activity, and fatigue. In the present study, no difference was observed in hand grip strength between the groups, while we found that QFM thickness was affected in patients with sarcoidosis when compared to the controls. The ultrasonographic QFM evaluation seems to be an innovative tool which may be used at all stages of sarcoidosis patient follow-up. The grip strength is a commonly used test to detect muscle weakness, but onset of a decrease in muscle mass in the lower extremities may occur earlier. Considering the increased burden of musculoskeletal problems in this population, performing 30s-CST and sonographic QFM thickness is practical methods to identify risky patients.

Kidney manifestations of sarcoidosis

Renal involvement is a clinically relevant organ manifestation of sarcoidosis, leading to increased morbidity and complications. Although the exact incidence remains unknown, renal disease is likely to occur in up to one third of all sarcoidosis patients. Every patient with newly diagnosed sarcoidosis should receive a renal work-up and screening for disrupted calcium metabolism.Amid various forms of glomerulonephritis, granulomatous interstitial nephritis is the most common one, but it rarely leads to renal impairment. Histologically, granulomas can be absent. Nephrocalcinosis and nephrolithiasis are frequent forms when hypercalcaemia or hypercalciuria occur. Drugs used for treatment of systemic sarcoidosis can also cause renal damage.Due to its high heterogeneity, renal sarcoidosis can be difficult to treat. Glucocorticoids and various immunosuppressive treatments have been proven to be effective based on case series, but clinical trials are lacking. A treatment guideline for renal sarcoidosis is urgently needed.In this review article, we present an overview of the different forms of renal sarcoidosis and the diagnostic steps to confirm renal involvement; in addition, we provide insights on the management and available treatments. A better understanding regarding the pathogenesis of sarcoidosis is the key for the development of more specific, targeted therapies.

The usefulness of speckle tracking echocardiography for the prediction of cardiac involvement in patients with biopsy-proven sarcoidosis.

Cardiac sarcoidosis (CS) is commonly diagnosed based on clinical criteria and abnormalities in noninvasive imaging reported in patients with biopsy-proven extracardiac sarcoidosis. Electrocardiogram and two-dimensional echocardiography have a low sensitivity for CS detection. Cardiovascular magnetic resonance imaging (CMR) and positron emission tomography (PET) have limitations in terms of cost and availability. This study aimed to assess the usefulness of left ventricular longitudinal strain, measured using two-dimensional speckle tracking echocardiography (STE), for the prediction of late gadolinium enhancement (LGE) presence in CMR in patients with biopsy-proven sarcoidosis. A total of 119 patients with biopsy-proven extracardiac sarcoidosis were divided, according to the clinical criteria proposed by the 2014 Heart Rhythm Society expert consensus statement (HRS 2014), into two groups: 43 individuals with "probable cardiac sarcoidosis", CS(+) and 76 individuals without cardiac sarcoidosis, CS (-). Data from echocardiography, CMR, 12-lead ECG and 24h Holter monitoring were analyzed. Left ventricular global longitudinal strain (LV-GLS) was slightly reduced in the entire sarcoidosis group (-18.61±2.96), no difference between the CS (+) and CS (-) subgroups was found (-18.0%±3.2% and -18.9%±2.8%, respectively; p=.223). No cut-off value for LV-GLS was identified that could predict the presence of LGE. Segmental longitudinal strain impairment partially correlated with the presence of LGE on CMR. In our cohort of sarcoidosis patients, segmental longitudinal strain proved more helpful in the diagnostic process than LV-GLS. The ultimate role of STE in the diagnosis of CS remains to be established.

Clinical Pharmacology in Sarcoidosis: How to Use and Monitor Sarcoidosis Medications.

When sarcoidosis needs treatment, pharmacotherapy is usually required. Although glucocorticoids work reliably and relatively quickly for sarcoidosis, these drugs are associated with numerous significant side effects. Such side effects are common in sarcoidosis patients, as the disease frequently has a chronic course and glucocorticoid treatment courses are often prolonged. For these reasons, corticosteroid-sparing and corticosteroid-replacing therapies are often required for sarcoidosis. Unfortunately, many healthcare providers who care for sarcoidosis patients are not familiar with the use of these agents. In this manuscript, we provide a review of the pharmacotherapy of sarcoidosis. We discuss the mechanism of action, dosing, side-effect profile, approach to monitoring and patient counselling concerning glucocorticoids, and the common alternative drugs recommended for use in the recent European Respiratory Society (Lausanne, Switzerland) Sarcoidosis Treatment Guidelines. We also discuss the use of these agents in special situations including hepatic insufficiency, renal insufficiency, pregnancy, breastfeeding, vaccination, and drug-drug interactions. It is hoped that this manuscript will provide valuable practical guidance to clinicians who care for sarcoidosis patients.

Activin A levels are raised during human tuberculosis and blockade of the activin signaling axis influences murine responses to M. tuberculosis infection.

Tuberculosis remains the leading cause of death by a bacterial pathogen. The etiologic agent of tuberculosis, Mycobacterium tuberculosis, can remain dormant in the infected host for years before causing disease. Significant effort has been made to identify biomarkers that can discriminate between latently infected and actively diseased individuals. We found that serum levels of the cytokine activin A were associated with increased lung pathology and could discriminate between active tuberculosis and tuberculin skin-test-positive healthy controls. Activin A signals through the ActRIIB receptor, which can be blocked by administration of the ligand trap ActRIIB-Fc, a soluble activin type IIB receptor fused to human IgG1 Fc. In a murine model of tuberculosis, we found that ActRIIB-Fc treatment reduced mycobacterial loads. Strikingly, ActRIIB-Fc treatment significantly increased the number of tissue-resident memory T cells. These results suggest a role for ActRIIB signaling pathways in host responses to Mycobacterium tuberculosis and activin A as a biomarker of ongoing disease.

Ocular sarcoidosis, to screen or not to screen?

Ocular sarcoidosis most commonly presents with symptoms and is first diagnosed before systemic sarcoidosis in at least half of the patients with sarcoidosis. Prevalence of ocular involvement in sarcoidosis varies between 2-80% depending on the study setting, included ocular diseases, and studied population. In many studies, ocular involvement in sarcoidosis has been overestimated mainly because study populations have been collected from eye clinics and because the study criteria have included ocular findings or symptoms that do not require treatment or monitoring. In a screening setting, asymptomatic ocular sarcoidosis has been detected in only 2-5%. 0-1% of the screened sarcoidosis patients have required treatment. For these reasons, ocular screening in sarcoidosis seems generally of little value. Patients with sarcoidosis who present with ocular symptoms should be screened for ocular sarcoidosis in a timely manner because they are at high risk of ocular disease.

Aberrant Lipid Metabolism in Macrophages Is Associated with Granuloma Formation in Sarcoidosis.

Rationale: Chronic sarcoidosis is a complex granulomatous disease with limited treatment options that can progress over time. Understanding the molecular pathways contributing to disease would aid in new therapeutic development. Objectives: To understand whether macrophages from patients with nonresolving chronic sarcoidosis are predisposed to macrophage aggregation and granuloma formation and whether modulation of the underlying molecular pathways influence sarcoidosis granuloma formation. Methods: Macrophages were cultivated invitro from isolated peripheral blood CD14+ monocytes and evaluated for spontaneous aggregation. Transcriptomics analyses and phenotypic and drug inhibitory experiments were performed on these monocyte-derived macrophages. Human skin biopsies from patients with sarcoidosis and a myeloid Tsc2-specific sarcoidosis mouse model were analyzed for validatory experiments. Measurements and Main Results: Monocyte-derived macrophages from patients with chronic sarcoidosis spontaneously formed extensive granulomas invitro compared with healthy control participants. Transcriptomic analyses separated healthy and sarcoidosis macrophages and identified an enrichment in lipid metabolic processes. In vitro patient granulomas, sarcoidosis mouse model granulomas, and those directly analyzed from lesional patient skin expressed an aberrant lipid metabolism profile and contained increased neutral lipids. Conversely, a combination of statins and cholesterol-reducing agents reduced granuloma formation both invitro and invivo in a sarcoidosis mouse model. Conclusions: Together, our findings show that altered lipid metabolism in sarcoidosis macrophages is associated with its predisposition to granuloma formation and suggest cholesterol-reducing therapies as a treatment option in patients.

Immune mapping of human tuberculosis and sarcoidosis lung granulomas.

Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB and sarcoidosis patients using in situ sequencing (ISS) transcriptomic analysis and multiplexed immunolabeling of tissue sections. TB lesions consisted of large necrotic and cellular granulomas, whereas "multifocal" granulomas with macrophages or epitheloid cell core and a T-cell rim were observed in sarcoidosis samples. The necrotic core in TB lesions was surrounded by macrophages and encircled by a dense T-cell layer. Within the T-cell layer, compact B-cell aggregates were observed in most TB samples. These B-cell clusters were vascularized and could contain defined B-/T-cell and macrophage-rich areas. The ISS of 40-60 immune transcripts revealed the enriched expression of transcripts involved in homing or migration to lymph nodes, which formed networks at single-cell distances in lymphoid areas of the TB lesions. Instead, myeloid-annotated regions were enriched in CD68, CD14, ITGAM, ITGAX, and CD4 mRNA. CXCL8 and IL1B mRNA were observed in granulocytic areas in which M. tuberculosis was also detected. In line with ISS data indicating tertiary lymphoid structures, immune labeling of TB sections expressed markers of high endothelial venules, follicular dendritic cells, follicular helper T cells, and lymph-node homing receptors on T cells. Neither ISS nor immunolabeling showed evidence of tertiary lymphoid aggregates in sarcoidosis samples. Together, our finding suggests that despite their heterogeneity, the formation of tertiary immune structures is a common feature in granulomas from TB patients.

Prevalence of Tuberculosis Infection among Various Risk Groups in India: A Systematic Review and Meta-Analysis.

Treatment of tuberculosis (TB) infection (TBI) to prevent active TB disease is a key component of the National Strategic Plan to end TB in India, without which the strategies to end TB would be futile. There is a need to rapidly scale up access to effective shorter regimens for tuberculosis preventive treatment (TPT) to a wider set of risk groups. This applies for identifying high-risk groups for TPT expansion. Thus, our aim with this review is to determine the TBI prevalence in different risk groups in India. We searched databases like Embase, Medline, Scopus, and CINAHL for studies published between 2012 and 2023 to estimate TBI in different risk groups in India. The PRISMA guidelines were followed when reviewing the publications, and a predetermined search strategy was used to find relevant sources across various databases. Using MetaXL (MS excel) software, we pooled data based on a random-effects model, along with heterogeneity testing using Cochrane's Q and I2 statistic. A total of 68 studies were included from 10,521 records. TBI pooled prevalence was estimated using the IGRA data, while in the absence of IGRA data, TST data were utilized. The key findings revealed a total of 36% pooled TBI prevalence for all risk factors, 59% among smokers, 53% among diabetics and alcoholics, 48% among malnourished, 47% among contacts of TB patients, 44% among HIV, 36% among pregnant women, 35% among COVID-19 patients, 31% among healthcare workers, 18% among sarcoidosis patients, and 15% among rheumatoid arthritis patients in India. Our review depicted a high TBI burden among groups such as diabetes mellitus, smokers, malnourished, and alcoholics. WHO has yet to recommend for systematic screening and treatment for TBI among these groups for want of evidence which this study provides, highlighting the need to reprioritize the risk groups for tailored TPT strategies.

Joint involvement in sarcoidosis: systematic review and meta-analysis of prevalence, clinical pattern and outcome.

To characterize joint involvement (JI) in sarcoidosis, a systematic search of MEDLINE, EMBASE and Cochrane Library was conducted from inception to July 2022 for publications reporting its prevalence, pattern, treatment and outcome. The pooled prevalence estimates (PPE) with 95% CI were calculated using binomial distribution and random effects. Meta-regression method was used to examine factors affecting heterogeneity between studies. Forty-nine articles were identified comprising a total of 8574 sarcoidosis patients, where 12% presented with JI (95% CI 10, 14; I2 = 0%). The PPE for sarcoid arthritis (SA) was 19% (95% CI 14, 24; I2 = 95%), and 32% (95% CI 13, 51; I2 = 99%) for arthralgia. Heterogeneity was due to higher JI prevalence reported in Western Asia and the Middle East, in rheumatology clinics and via surveys. Sample size of SA varied from 12 to 117 cases. Ankles were most frequently affected (PPE 80%) followed by knees and wrists. Monoarthritis was uncommon (PPE 1%; 95% CI 0, 2; I2 = 55%). Acute SA prevailed (PPE 79%; 95% CI 72, 88; I2 = 69%) with an equal proportion of oligo and polyarthritis and was frequently accompanied by erythema nodosum (PPE 62%; 95% CI 52, 71; I2 = 16%). Chronic SA was predominantly polyarticular with a higher frequency of the upper extremity joints affected. Most common non-articular manifestations with SA included fever (52%), erythema nodosum (41%), hilar adenopathy (86%) and interstitial lung disease (23%) of which one-third required corticosteroids and/or immunosuppressants. SA occurred early in the disease with a PPE of 19% and most frequent pattern of acute oligo- or polyarthritis predominantly affecting the lower extremity large joints.

DECODING MICROBIOME DYSBIOSIS THROUGH METAGENOMIC ALPHA DIVERSITY

Background: Sarcoidosis is a chronic inflammatory disease that can affect multiple organs. The aetiology of sarcoidosis is not fully understood, but there is increasing evidence that the microbiome may play a role. The blood microbiome is a collection of microorganisms that live in the bloodstream. It is a complex and dynamic community that is influenced by a variety of factors, including the host’s lifestyle and pathology. Recent studies have shown that people with sarcoidosis have alterations in their blood microbiome. These alterations include changes in the diversity, richness, and evenness of the microbial community. The abundance measures by which the blood microbiome diversity may detect instances of dysbiosis related to sarcoidosis aetiology. It should be clearly distinguished from microbiome changes related to unspecific inflammation or sepsis. However, the available evidence suggests that the microbiome may be a promising target for therapeutic interventions. Aim: The primary goal of this review was to assess and compare the existing metrics of microbiome composition and diversity as established by metagenomic analyses. Additionally, we aim to elucidate the potential causal relationship between these measures, the phenomenon of blood microbiome dysbiosis and the pathogenesis of sarcoidosis. Conclusion: In the present review, we investigated alpha diversity measures as characteristics of microbiome communities, examining their potential as indicators of dysbiosis, and the probablemechanisms of microbiome participation. A descriptive qualitative comparison was conducted between lung microbiome data of sarcoidosis patients and blood microbiome data of healthy adults. This comparison elucidates common taxa between the two microbiomes and identifies taxa potentially involved in sarcoidosis.