Pannus Formation Research Articles

Subaortic Pannus Causing Complete Outlet Obstruction After Bioprosthetic Aortic Valve Replacement in a Patient with Left Ventricular Assist Device: A Case Report

Abstract Background Subaortic pannus formation complicates bioprosthetic aortic valve(AV) replacement. We report an extreme case in a continuous-flow left-ventricular-assist-device(LVAD) patient. Case Summary A 49-year-old Caucasian female with dilated cardiomyopathy was bridged-to-transplant with a HeartWare ventricular-assist-device(HVAD). Duration of support was prolonged, 6-years and 7-months, due to allosensitisation requiring desensitisation. Pump thrombosis occurred 2-years and 4-months post-LVAD requiring alteplase thrombolysis. The patient underwent bioprosthetic AV replacement 3-years and 10-months post-LVAD for symptomatic aortic incompetence. Transthoracic echocardiography(TTE) performed 1-year and 2-years post-bioprosthetic AV replacement repeatedly demonstrated an AV closed during all cardiac cycles without incompetence and nil flow through the left-ventricular-outflow-tract(LVOT). Following transplant, analysis of explanted heart revealed a fused AV. A pannus adherent to the underside of the AV had formed across the entire AV outlet, with complete obliteration of LVOT. This subaortic pannus was not visualised on previous TTE. Histologically, the pannus consisted of hypocellular fibrous tissue with chronic inflammatory cells, spindle histiocytes and myofibroblasts scattered throughout the loose fibromyxoid stroma, the latter highlighted on CD68 immunohistochemical stain(IHC). Partial endothelialisation on the pannus surface was highlighted on ERG & CD31 IHC. Neither calcification, nor signs of acute inflammation were noted. In contrast to previous cases, there was no evidence of associated thrombus macroscopically or microscopically. Discussion Prolonged LVAD support may facilitate subaortic pannus following bioprosthetic AV replacement due to AV closure and altered transvalvular flow. Due to the parallel LVAD circulation, subaortic pannus may develop asymptomatically, without haemodynamic compromise, allowing progression to total LVOT obstruction. This requires consideration prior to LVAD explantation in bridge-to-recovery patients.

A Large Calf Mass in a Patient with Rheumatoid Arthritis: Giant Pannus Filling Baker’s Cyst

Abstract Rheumatoid arthritis (RA) presents a significant challenge among autoimmune diseases, affecting millions globally with diverse clinical manifestations, primarily targeting joints and inducing inflammation, pain, and deformities. In some cases, it leads to the formation of Bakers cysts, fluid-filled bursae in the popliteal region, resulting from chronic inflammation of the synovial membrane and subsequent pannus growth. Our case, a young female patient with RA, presenting with calf mass, highlights this complex interplay. She presented with large swelling and pain in her left calf region which on high-frequency ultrasound revealed a large, well-defined heteroechoic mass lesion distending bursa between the medial head of the gastrocnemius and semimembranosus muscle, measuring 25 cm craniocaudally, without any color Doppler abnormality. Ultrasound-guided biopsy was performed to rule out the possibility of sarcoma and it revealed inflammatory changes. Final diagnosis of excessive pannus formation within the Baker’s cyst forming large mass was made, with RA identified as the underlying cause. The differential diagnosis of masses in the popliteal fossa includes synovial/meniscal/ganglion cysts, lipomas, vascular pathologies, and neoplastic conditions. High-resolution ultrasound is an important diagnostic modality for evaluating popliteal fossa masses. Magnetic resonance imaging is typically performed to assess for neoplastic causes and internal derangement of the knee. Our case of a massive pannus filling a Baker’s cyst in the context of RA emphasizes the intricate nature of the disease and its diverse clinical expressions. It is important for the radiologist to be aware of this imaging appearance for timely diagnosis and management.

The degenerated glenohumeral joint.

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy.

Endothelial mesenchymal transition promotes pannus formation in ankylosing spondylitis byactivation of TGF-β/SMAD signalling pathway.

To explore the role of endothelial-mesenchymal transition (EndMT) mediated by the TGF-β/SMAD signalling pathway in the pathogenesis of ankylosing spondylitis (AS). Serum levels of TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA) in 48 patients with AS and 15 healthy subjects. The expression levels of TGF-β1, SMAD7, CTGF, CD34 and EndMT-related markers (α-SMA, vimentin, FSP-1, VE-cadherin) in the sacroiliac joint (SIJ) of three AS patients were detected by immunohistochemistry, and three non-spondyloarthritis (SpA) autopsy samples were used as controls. Serum TGF-β1 level of AS patients was significantly higher than that of healthy controls (22971 ± 7667 pg/ml vs. 14837±4653 pg/ml, p<0.01). Compared with the non-SpA control group, the microvascular density (MVD) at the pannus formation site of SIJ in AS patients was significantly increased, accompanied by respectively increased expressions of TGF-β1, CTGF, α-SMA, vimentin, and FSP-1 (all p<0.05), whereas respectively decreased expressions of VE-cadherin and SMAD7 (p<0.01). The expression level of FSP-1 was positively correlated with levels of TGF-β1 and MVD, and negatively correlated with SMAD7. Our findings show that EndMT is involved in the promotion of pannus formation by TGF-β/SMAD signalling pathway activation in AS.

Tujia medicine Toddalia asiatica improves synovial pannus in rats with collagen-induced arthritis through the PI3K/Akt signaling pathway

To investigate the therapeutic mechanism of Tujia medicine Toddalia asiatica alcohol extract (TAAE) for synovial pannus formation in rats with college-induced arthritis (CIA). Sixty male SD rats were randomized into normal control group, CIA model group, TGT group, 3 TAAE treatment groups at low, medium and high doses (n=10). Except for those in the normal control group, all the rats were subjected to CIA modeling using a secondary immunization method and treatment with saline, TGT or TAAE by gavage once daily for 35 days. The severity of arthritis was assessed using arthritis index (AI) score, and knee joint synovium pathologies were examined with HE staining. Serum levels of TNF-α, IL-6, and IL-1β were detected with ELISA; the protein expressions of PI3K, Akt, p-PI3K, p-Akt, VEGF, endostatin, HIF-1α, MMP1, MMP3, and MMP9 in knee joint synovial tissues were determined using Western blotting, and the mRNA expressions of TNF‑α, IL-6, IL-1β, VEGF, HIF-1α, PI3K, and Akt were detected with RT-PCR. Treatment of CIA rat models with TAAE and TGT significantly alleviated paw swelling, lowered AI scores, and reduced knee joint pathology, neoangiogenesis, and serum levels of inflammatory factors. TAAE treatment obviously increased endostatin protein expression, downregulated p-PI3K, p-Akt, MMP1, MMP3, MMP9, VEGF, and HIF-1α proteins, and reduced TNF‑α, IL-6, IL-1β, PI3K, Akt, VEGF, and HIF-1α mRNA levels in the synovial tissues, and these changes were comparable between high-dose TAAE group and TGT group. TAAE can improve joint symptoms and inhibit synovial pannus formation in CIA rats by regulating the expressions of HIF-1α, VEGF, endostatin, MMP1, MMP3, and MMP9 via the PI3K/Akt signalling pathway.

Chronic osteoarthritis caused by Propionibacterium australiense infection in a captive sand gazelle.

Osteoarthritis is a common cause of morbidity and mortality in geriatric gazelles. Propionibacterium australiense has been reported as a cause of systemic granulomas in cattle, but there are no descriptions of this bacteria infecting other species nor causing osteoarthritis, to our knowledge. An 8-y-old, castrated male, sand gazelle (Gazella leptoceros leptoceros) was managed for chronic, intermittent, progressive osteoarthritis of the right tarsus. Serial biopsies revealed pyogranulomatous dermatitis with intralesional bacteria. Serial diagnostic imaging identified osseous and soft tissue proliferation with draining tracts. Treatments over 1 y included broad-spectrum antibiotics, anti-inflammatories, joint debridement, and infusion with platelet-rich plasma and stem cells. Despite therapy, lameness persisted, azotemia developed, and subsequently, the animal was euthanized. On postmortem examination, the periarticular tissue of the right tarsus was markedly expanded by pyogranulomas and fibrosis. Histologically, the synovium, joint capsule, and overlying soft tissues were markedly expanded by pyogranulomas and numerous gram-positive and acid-fast-negative filamentous bacteria surrounded by Splendore-Hoeppli material. Within the joint, there was regionally extensive cartilage ulceration, osteonecrosis, osteolysis, and pannus formation. PCR assay of affected formalin-fixed, paraffin-embedded tissue amplified segments of 16S rRNA and β subunit of bacterial RNA polymerase (rpoB) genes with 99.7% and 95.6% identity to P. australiense. This bacterium should be considered a differential for chronic pyogranulomatous osteoarthritis in gazelles.

Targeting next-generation PDE4 inhibitors in search of potential management of rheumatoid arthritis and psoriasis

Immune-mediated inflammatory diseases (IMIDs) comprise a broad spectrum of conditions characterized by systemic inflammation affecting various organs and tissues, for which there is no known cure. The isoform-specific inhibition of phosphodiesterase-4B (PDE4B) over PDE4D constitutes an effective therapeutic strategy for the treatment of IMIDs that minimizes the adverse effects associated with non-selective PDE4 inhibitors. Thus, we report a new class of isoquinolone derivatives as next-generation PDE4 inhibitors for effective management of rheumatoid arthritis (RA) and psoriasis. Among the series, 8 compounds i.e. 1e, 1l, 1m, 1n, 1o, 2m, 2o and 3o showed promising PDE4B inhibition (>80 %) in vitro with IC50 ∼ 1.4–6.2 µM. The compound 1l was identified as an initial hit and was pursued for further studies. According to structure–activity relationship (SAR), an allyl group at C-4 position improved PDE4B inhibition. The correlation between in vitro activity data and binding affinities obtained via molecular docking suggested that the high-affinity binding to PDE4B is a prerequisite for the effective inhibition of PDE4B. Notably, the hit 1l showed selectivity towards PDE4B over PDE4D in vitro. Furthermore, 1l treatment (30 mg/kg) in the adjuvant-induced arthritis (AIA) rat model induced by complete Freund’s adjuvant (CFA) demonstrated anti-arthritic potential via ameliorating paw swelling and body weight, narrowing joint space, reducing excessive immune cells infiltration and pannus formation in addition to reducing mRNA expression of pro-inflammatory cytokines such as TNF-α and IL-6 in synovial tissues of experimental rats. Additionally, 1l reduced the hyper-proliferative state and colony forming potential of IMQ-induced psoriatic keratinocytes. The treatment of these cells with 1l markedly reduced the protein levels of Ki67 and mRNA levels of pro-inflammatory cytokines e.g. IL-17A and TNF-α suggesting its potent anti-psoriatic potential. Furthermore, 1l did not show any significant adverse effects when evaluated in a systematic toxicity (e.g. teratogenicity, hepatotoxicity and cardiotoxicity) studies in zebrafish at the tested concentrations (1–100 µM) and the NOAEL (no-observed-adverse-effect level) was found to be 100 µM. Thus, with promising anti-inflammatory effects both in vitro and in vivo along with PDE4B selectivity with an acceptable safety margin, 1l emerged as a new and promising inhibitor for further studies.

Melatonin hyalurosomes in collagen thermosensitive gel as a potential repurposing approach for rheumatoid arthritis management via the intra-articular route

Despite the fact that several rheumatoid arthritis treatments have been utilized, none of them achieved complete joint healing and has been accompanied by several side effects that compromise patient compliance. This study aims to provide an effective safe RA treatment with minimum side effects through the encapsulation of melatonin (MEL) in hyalurosomes and loading these hyalurosomes in collagen thermos-sensitive poloxamer 407 (PCO) hydrogels, followed by their intra-articular administration in AIA model rats. In vitro characterization of MEL-hyalurosomes and PCO hydrogel along with in vivo evaluation of the selected formulation were conducted. Particle size, PDI and EE % of the selected formulation were 71.5 nm, 0.09 and 90 %. TEM micrographs demonstrated that the particles had spherical shape with no aggregation signs. Loading PCO hydrogels with MEL-hyalurosomes did not cause significant changes in pH although it increased its viscosity and injection time. FTIR analysis showed that no interactions were noted among the delivery system components. In vivo results revealed the superior effect of MEL-hyalurosomes PCO hydrogel over MEL-PCO hydrogel and blank PCO hydrogels in improving joint healing, cartilage repair, pannus formation and cell infiltrations. Also, MEL-hyalurosomes PCO hydrogel group showed comparable levels of TNF-α, IL1, MDA, NRF2 and HO-1 with the negative control group. These findings highlight the MEL encapsulation role in augmenting its pharmacological effects along with the synergistic effect of hyaluronic acid in hyalurosomes and collagen in PCO hydrogel in promoting joint healing.

A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys joints and cartilage, resulting in synovitis and pannus formation. Timely detection and effective management of RA are pivotal for mitigating inflammatory arthritis consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents a promising avenue for RA diagnosis and response to treatment assessment. Radiopharmaceutical such as technetium-99m (99mTc), combined with single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), introduces a more refined diagnostic approach, enhancing accuracy through precise anatomical localization, representing a notable advancement in hybrid molecular imaging for RA evaluation. This comprehensive review discusses existing research, encompassing in vitro, in vivo, and clinical studies to explore the application of 99mTc radiolabeled targeting vectors with SPECT imaging for RA diagnosis. The purpose of this review is to highlight the potential of this strategy to enhance patient outcomes by improving the early detection and management of RA.

Unveiling Novel Drug Targets and Emerging Therapies for Rheumatoid Arthritis: A Comprehensive Review.

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a "treat-to-target" approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs.

Free Fatty Acid 4 Receptor Activation Attenuates Collagen-Induced Arthritis by Rebalancing Th1/Th17 and Treg Cells.

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) has been found to be beneficial in rodent rheumatoid arthritis models and human trials. However, the molecular targets of n-3 PUFAs and their beneficial effects on rheumatoid arthritis are under-researched. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor for n-3 PUFA. We aim to investigate whether FFA4 activation reduces collagen-induced rheumatoid arthritis (CIA) by using an FFA4 agonist, compound A (CpdA), in combination with DBA-1J Ffa4 gene wild-type (WT) and Ffa4 gene knock-out (KO) mice. CIA induced an increase in the arthritis score, foot edema, synovial hyperplasia, pannus formation, proteoglycan loss, cartilage damage, and bone erosion, whereas the administration of CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA increased mRNA expression levels of pro-inflammatory Th1/Th17 cytokines, whereas CpdA significantly suppressed those increases in Ffa4 WT mice but not Ffa4 gene KO mice. CIA induced an imbalance between Th1/Th17 and Treg cells, whereas CpdA rebalanced them in spleens from Ffa4 WT mice but not Ffa4 gene KO mice. In SW982 synovial cells, CpdA reduced the LPS-induced increase in pro-inflammatory cytokine levels. In summary, the present results suggest that the activation of FFA4 in immune and synovial cells could suppress the characteristics of rheumatoid arthritis and be an adjuvant therapy.

Circumferential Pannus at C1-C2 Causing Spinal Cord Compression

Periodontoid pannus formation is a pathologic condition caused by a multitude of different etiologies, however, it is most commonly due to rheumatoid arthritis. In these cases, the pannus is typically located in the retro-odontoid space ventral to the spinal cord, leading to progressive neural compression. We describe in this report, a patient who presented with progressive high cervical myelopathy, who on imaging revealed both a retro-odontoid pannus and a posterior C1-C2 mass causing severe circumferential compression of the spinal cord. The patient was successfully treated with a C1-C2 laminectomy and occipitocervical fusion. Periodontoid pannus is a common entity; however, the presence of a C1-C2 posterior pannus is a unique finding. To our knowledge, circumferential pannus at C1-C2 causing neural compression is a clinical entity that has not been previously reported.

The Role of Mesenchymal Stromal Cells in the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies.

Inhibition of LSD1 via SP2509 attenuated the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Lysine-specific demethylase 1 (LSD1), an enzyme involved in transcriptional regulation, has an unclear role in synovial inflammation, fibroblast-like synoviocytes migration, and invasion during RA pathogenesis. In this study, we observed increased LSD1 expression in RA synovial tissues and in TNF-α-stimulated MH7A cells. SP2509, an LSD1 antagonist, directly reduced LSD1 expression and reversed the elevated levels of proteins associated with inflammation, apoptosis, proliferation, and autophagy induced by TNF-α. Furthermore, SP2509 inhibited the migratory capacity of MH7A cells, which was enhanced by TNF-α. In CIA models, SP2509 treatment ameliorated RA development, reducing the expression of pro-inflammatory cytokines and alleviating joint pathological symptoms. These findings underscore the significance of LSD1 in RA and propose the therapeutic potential of SP2509.

Launaea fragilis extract attenuated arthritis in rats through modulation of IL-1β, TNF-α, IL-6, NF-κB, COX-2, IL-4, and IL-10.

Launaea fragilis (Asso) Pau is a Cholistan desert medicinal plant. Launaea species are used as traditional remedies against various inflammatory conditions. The current research was designed to evaluate the anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of L. fragilis (Et-LF). The plant extract was prepared by triple maceration. GC-MS screening explored the presence of various bioactive phytoconstituents including n-tetracosanol-1, 1-heptacosanol, and n-hexadecanoic acid. DPPH assay demonstrated the antioxidant potential of Et-LF. Safety profile data indicated that Et-LF was safe up to the oral dose of 5000mg/kg in female rats. Anti-nociceptive activity of Et-LF was assessed in hot plate method and acetic acid-induced writhing model and the results suggested that Et-LF had significant analgesic effects in both animal models. Carrageenan, histamine, and serotonin-induced edema models were used to estimate the anti-inflammatory effects of Et-LF and were found to prevent paw edema development dose dependently. The anti-arthritic effect of Et-LF was estimated in CFA-induced arthritic rat model. Treatment with Et-LF 125, 250, 500 and flurbiprofen (FP) 10mg/kg/day significantly attenuated the paw edema, reversed the reduced body weight, and restored the altered hematological parameters in arthritic rats. Gene expression studies revealed the significant downregulation of IL-1β, TNF-α, IL-6, NF‑κB, and COX-2, and upregulation of IL-4 and IL-10 in arthritic rats treated with various doses of plant extract. Histological evaluation of ankle joints showed that Et-LF mitigated pannus formation, infiltration of inflammatory cells, and fibrous connective tissue formation in the diseased rats. Thereof, it may be concluded that the recent study demonstrated the anti-nociceptive, anti-inflammatory, and anti-arthritic effects ascribed to the signifying presence of phytoconstituents in L. fragilis.

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory autoimmune condition characterized by synovitis, pannus formation (with adjacent bone erosion), and joint destruction. In the perpetuation of RA, fibroblast-like synoviocytes (FLSs), macrophages, B cells, and CD4+ T-cells-specifically Th1 and Th17 cells-play crucial roles. Additionally, dendritic cells, neutrophils, mast cells, and monocytes contribute to the disease progression. Monocytes, circulating cells primarily derived from the bone marrow, participate in RA pathogenesis. Notably, CCR2 interacts with CCL2, and CX3CR1 (expressed by monocytes) cooperates with CX3CL1 (produced by FLSs), facilitating the migration involved in RA. Canonical "classical" monocytes predominantly acquire the phenotype of an "intermediate" subset, which differentially expresses proinflammatory cytokines (IL-1β, IL-6, and TNF) and surface markers (CD14, CD16, HLA-DR, TLRs, and β1- and β2-integrins). However, classical monocytes have greater potential to differentiate into osteoclasts, which contribute to bone resorption in the inflammatory milieu; in RA, Th17 cells stimulate FLSs to produce RANKL, triggering osteoclastogenesis. This review aims to explore the monocyte heterogeneity, plasticity, antigenic expression, and their differentiation into macrophages and osteoclasts. Additionally, we investigate the monocyte migration into the synovium and the role of their cytokines in RA.

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, pannus formation and bone erosion. Various immune cells, including macrophages, are involved in RA pathogenesis. The heterogeneity and plasticity of macrophages render them pivotal regulators of both the induction and resolution of the inflammatory response. Predominantly, two different phenotypes of macrophages have been identified: classically activated M1 macrophages exacerbate inflammation via the production of cytokines, chemokines and other inflammatory mediators, while alternatively activated M2 macrophages inhibit inflammation and facilitate tissue repair. An imbalance in the M1/M2 macrophage ratio is critical during the initiation and progression of RA. Macrophage polarization is modulated by various transcription factors, epigenetic elements and metabolic reprogramming. Curcumin, an active component of turmeric, exhibits potent immunomodulatory effects and is administered in the treatment of multiple autoimmune diseases, including RA. The regulation of macrophage polarization and subsequent cytokine production as well as macrophage migration is involved in the mechanisms underlying the therapeutic effect of curcumin on RA. In this review, we summarize the underlying mechanisms by which curcumin modulates macrophage function and polarization in the context of RA to provide evidence for the clinical application of curcumin in RA treatment.

The visual impact of higher-order aberrations in patients with pediatric blepharokeratoconjunctivitis.

To analyze higher-order aberrations (HOAs) and their visual impact in a pediatric blepharokeratoconjunctivitis (PBKC) cohort compared with healthy controls. Prospective case-control study of pediatric patients (≤ 16 years old). Subjects underwent wavefront aberrometry analysis to compare HOAs and their impact on visual quality. A total of 150 eyes from 76 patients were included in the analysis. The PBKC group consisted of 50 eyes and the control group of 100 healthy eyes. Mean age was 10.39 ± 3.81 years for the PBKC group and 10.80 ± 3.61 years for the controls. Mean corrected-distance visual acuity (CDVA) was 0.24 ± 0.21 logMAR in the PBKC group and 0.07 ± 0.1 in the controls (P < 0.001). Mean astigmatism was 1.6 ± 1.98D in the PBKC group vs. 0.67 ± 0.76D in the control group (P = 0.01). Mean RMS of HOAs was 1.05 ± 1.7mm in the PBKC group and 0.41 ± 0.18mm in the controls (P < 0.001). The mean modulation transfer function (MTF) in the PBKC group was significantly lower (16.37 ± 16.32) than controls (30.3 ± 23.57) (P < 0.001). Corneal leukomas, stromal vascularization, peripheral nummular subepithelial scars, and pannus formation are associated with increased HOAs. There was a significant increase in total HOAs of eyes with PBKC compared to healthy controls. Corneal opacity, vascularization, and scarring are associated with increased HOAs. The PBKC eye aberration profile: coma, secondary astigmatism, quadrafoil, and pentafoil, were associated with decreased CDVA and visual quality (PSF and MTF).

A novel classification and management scheme for craniocervical junction disorders with ventral neural element compression.

Craniocervical junction (CCJ) pathologies with ventral neural element compression are poorly understood, and appropriate management requires accurate understanding, description, and a more uniform nomenclature. The aim of this study was to evaluate patients to identify anatomical clusters and better classify CCJ disorders with ventral compression and guide treatment. A retrospective review of adult and pediatric patients with ventral CCJ compression from 2008 to 2022 at a single center was performed. The incidence of anatomical abnormalities and compressive etiologies was assessed. Surgical approach, radiographic data, and outcomes were recorded. Association rules analysis (ARA) was used to assess variable clustering. Among 51 patients, the main causes of compression were either purely bony (retroflexed dens [n = 18]; basilar invagination [BI; n = 13]) or soft tissue (degenerative pannus [n = 16]; inflammatory pannus [n = 2]). The primary cluster in ARA was a retroflexed dens, platybasia, and Chiari malformation (CM), and the secondary cluster was BI, C1-2 subluxation, and reducibility. These, along with degenerative pannus, formed the three major classes. In assessing the optimal treatment strategy, reducibility was evaluated. Of the BI cases, 12 of the 13 patients had anterolisthesis of C1 that was potentially reducible, compared with 2 of the 18 patients with a retroflexed dens (both with concomitant BI), and no pannus cases. The mean C1-2 facet angle was significantly higher in BI at 32.4°, compared with -2.3° in retroflexed dens and 8.1° in degenerative pannus (p < 0.05). Endonasal decompression with posterior fixation was performed in 48 (94.0%) of the 51 patients, whereas posterior reduction/fixation alone was performed in 3 patients (6.0%). Of 16 reducible cases, open posterior reduction alone was successful in 3 (60.0%) of 5 cases, with all successes containing isolated BI. Reduction was not attempted if vertebral anatomy was unfavorable (n = 9) or the C1 lateral mass was absent (n = 5). The mean follow-up was 28 months. Symptoms improved in 88.9% of patients and were stable in the remaining 11.1%. Tracheostomy and percutaneous G-tube placement occurred in 7.8% and 11.8% of patients, respectively. Reoperation for an endonasal CSF leak repair or posterior cervical wound revision both occurred in 3.9% of patients. In classifying, one cluster caused decreased posterior fossa volume due to an anatomical triad of retroflexed dens, platybasia, and CM. The second cluster caused pannus formation due to degenerative hypertrophy. For both, endonasal decompression with posterior fixation was ideal. The third group contained C1 anterolisthesis characterized by a steep C1-2 facet angle causing reducible BI. Posterior reduction/fixation is the first-line treatment when anatomically feasible or endonasal decompression with in situ posterior fixation when anatomical constraints exist.

Tissue-engineered and autologous pericardium in congenital heart surgery: comparative histopathological study of human vascular explants.

The goal of this histological study was to assess the biocompatibility of vascular patches used in the repair of congenital heart defects. We examined tissue-engineered bovine (n = 7) and equine (n = 7) patches and autologous human pericardium (n = 7), all explanted due to functional issues or follow-up procedures. Techniques like Movat-Verhoeff, von Kossa and immunohistochemical staining were used to analyse tissue composition, detect calcifications and identify immune cells. A semi-quantitative scoring system was implemented to evaluate the biocompatibility aspects, thrombus formation, extent of pannus, inflammation of pannus, cellular response to patch material, patch degradation, calcification and neoadventitial inflammation. We observed distinct material degradation patterns among types of patches. Bovine patches showed collagen disintegration and exudate accumulation, whereas equine patches displayed edematous swelling and material dissolution. Biocompatibility scores were lower in terms of cellular response, degradation and overall score for human autologous pericardial patches compared to tissue-engineered types. The extent of pannus formation was not influenced by the type of patch. Bovine patches had notable calcifications causing tissue hardening, and foreign body giant cells were more frequently seen in equine patches. Plasma cells were frequently detected in the neointimal tissue of engineered patches. Our results confirm the superior biocompatibility of human autologous patches and highlight discernible variations in the changes of patch material and the cellular response to patch material between bovine and equine patches. Our approach implements the semi-quantitative scoring of various aspects of biocompatibility, facilitating a comparative quantitative analysis across all types of patches, despite their inherent differences.