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A 39-year-old man presented with both eyes limbal stem cell deficiency status post chemical injury. He was managed initially with topical medications to subside the ocular surface inflammation. Over the course of subsequent visits, the fibrovascular pannus over the cornea gradually progressed, leading to further diminution of vision in left eye more than right eye. Since, the ocular surface was wet, the patient committed for lifelong immunosuppression and his brother consented to donate healthy limbal tissue; he underwent living-related allogeneic simple limbal epithelial transplantation in the left eye.

BACKGROUND In patients with prosthetic heart valves (PHV), there are distinct treatment implications based on prosthetic valve dysfunction (PVD) etiology. We investigated whether evaluation for PVD etiology on computed tomography (CT) has prognostic value for adverse clinical outcomes. METHODS Consecutive patients with suspected PVD that had a clinically indicated contrast chest CT and echocardiogram done within 1 year of each other were identified retrospectively from the Prosthetic Heart Valve CT Registry at the University of Minnesota. CTs and echocardiograms were assessed for potential PVD etiologies of pannus, structural valve degeneration (SVD) and thrombus, as per standard guidelines. Kaplan-Meier and Cox regression analyses were performed to assess association with a composite outcome of reoperation and all-cause mortality. RESULTS 132 patients (51.5% male, mean age 62.1 ​± ​19.3 years) with suspected PVD were included. There were 97 tissue valves, 31 mechanical valves and 4 transcatheter valves. The location of the valve was as follows: 72 aortic, 45 mitral, 8 tricuspid, and 7 pulmonic. A PVD etiology was diagnosed on CT in 80 (60.6%) patients, and on echocardiography in 45 (34.1%) patients, largely driven by a diagnosis of SVD on both modalities. Significant univariate predictors of the composite outcome included CT diagnosis of SVD (P ​

Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus, which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund’s Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1βand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.

OBJECTIVEThe endoscopic endonasal approach (EEA) to the lower clivus and craniovertebral junction (CVJ) has been traditionally performed via resection of the nasopharyngeal soft tissues. Alternatively, an inferiorly based rhinopharyngeal (RP) flap (RPF) can be dissected to help reconstruct the postoperative defect and separate it from the oropharynx. To date, there is no evidence regarding the viability and potential clinical impact of the RPF. The aim of this study was to assess RPF viability and its impact on clinical outcome.METHODSA retrospective cohort of 60 patients who underwent EEA to the lower clivus and CVJ was studied. The RPF was used in 30 patients (RPF group), and the nasopharyngeal soft tissues were resected in 30 patients (control group).RESULTSChordoma was the most common surgical indication in both groups (47% in the RPF group vs 63% in the control group, p = 0.313), followed by odontoid pannus (20% in the RPF group vs 10%, p = 0.313). The two groups did not significantly differ in terms of extent of tumor (p = 0.271), intraoperative CSF leak (p = 0.438), and skull base reconstruction techniques other than the RPF (nasoseptal flap, p = 0.301; fascia lata, p = 0.791; inlay graft, p = 0.793; and prophylactic lumbar drain, p = 0.781). Postoperative soft-tissue enhancement covering the lower clivus and CVJ observed on MRI was significantly higher in the RPF group (100% vs 26%, p < 0.001). The RPF group had a significantly lower rate of nasoseptal flap necrosis (3% vs 20%, p = 0.044) and surgical site infection (3% vs 27%, p = 0.026) while having similar rates of postoperative CSF leakage (17% in the RPF group vs 20%, p = 0.739) and meningitis (7% in the RPF group vs 17%, p = 0.424). Oropharyngeal bacterial flora dominated the infections in the control group but not those in the RPF group, suggesting that the RPF acted as a barrier between the nasopharynx and oropharynx.CONCLUSIONSThe RPF provides viable vascularized tissue coverage to the lower clivus and CVJ. Its use was associated with decreased rates of nasoseptal flap necrosis and local infection, likely due to separation from the oropharynx.

Background Connective tissue growth factor (CTGF)-induced angiogenesis is a crucial factor in rheumatoid arthritis (RA), but CTGF-interacting protein and related molecular mechanism of their interaction have not been fully elucidated. Methods CTGF-interacting proteins were identified through the LC-MS/MS analysis of the Co-IP products from fibroblast-like synoviocyte (FLS) lysates, and the interaction between CTGF and annexin A2 (ANXA2) was further confirmed through Co-IP and BiFC assay. The binding domain, mutant, mechanism, and angiogenesis function were assessed by homology modeling, molecular docking, MTT, cell scratch, tube formation, and chick chorioallantoic membrane (CAM) assays. Additionally, severe combined immunodeficiency (SCID) mouse co-implantation model was constructed to confirm the effect of ANXA2/CTGF-TSP1 in the process of RA in vivo. Results ANXA2 was identified and verified as an interaction partner of CTGF for the first time by Co-IP and LC-MS/MS analysis. Co-localization of CTGF and ANXA2 was observed in RA-FLS, and direct interaction of the TSP-1 domain of CTGF and ANXA2 was determined in HEK293T cells. The spatial conformation and stable combination of the ANXA2/CTGF-TSP1 complex were assessed by homology modeling in the biomimetic environment. The function of the ANXA2/CTGF-TSP1 complex was proved on promoting FLS proliferation, migration, and angiogenesis in vitro and deteriorating FLS invasion and joint damage in SCID mice. Conclusions TSP-1 is the essential domain in CTGF/ANXA2 interaction and contributes to FLS migration and pannus formation, inducing the process of RA.

Osteoclasts have a unique capacity to destroy bone, playing key roles in physiological bone remodeling and arthritic bone erosion. It is not known whether the osteoclast populations in different tissue settings arise from similar monocytoid precursors. The rapid progress in the next-generation sequencing technologies has provided many valuable insights into the field of osteoimmunology, and single-cell RNA sequencing (scRNA-Seq) can elucidate cellular heterogeneity within the synovial microenvironment. The application of scRNA-Seq to the defined osteoclast precursor (OP)-containing population enabled the identification of individual cells differentiating into mature osteoclasts in the inflamed synovium, which were distinct from conventional OPs in the bone marrow. In addition, an intravital imaging system using multi-photon microscopy has been applied to the synovial tissues of arthritic mice to observe the real-time dynamics of osteoclasts and immune cells in the pannus. These technologies have contributed to elucidate the transcriptomics and dynamics of specific cells involved in pathological osteoclastogenesis, improving our understand of the pathophysiology of inflammatory osteolytic diseases. Here, we review how novel technologies such as scRNA-Seq and intravital imaging help to better understand the pathogenesis of bone erosion and we introduce recent studies that have identified and directly visualized pathological OPs in inflamed synovium.

Osteoarthritis occurs when protective cartilage of bones worn out. Similarlty, cartilage damage occurs mainly in the pannus cartilage in rheumatoid arthritis. It is a potentially debilitating condition, affecting women two to three times more often than men. The cause and prognosis of rheumatoid and osteoarthritis are still poorly known. However, advances in the study of disease pathogenesis have encouraged the creation of new therapeutics with improved outcomes. The purpose of this study is to investigate the differentially expressed genes potentially involved in dysregulated rheumatoid arthritis (RA) and their association to other types of arthritis, including osteoarthritis (OA). Complete RNAs were isolated for RNA expression profiling using next-generation sequencing from human primary cultured normal and RA chondrocytes. From RNA sequencing results 250 differentially expressed genes were identified using bioinformatics analysis, of which 32 were found to be significantly playing role in RA pathogenesis and its associated diseases. Molecular ontologies of the identified genes showed they are connected to Innate immune response, Protein phosphorylation, Transcription initiation from RNA polymerase II promoter, Immune response, Neoplasms of bones, as well as osteorthritis, and Rheumatoid arthritis. Among the identified genes, TRAF1, TRAF2, BAMP, STX11, MEOX2, AES, REL, FHL3, PNMA1, SGTA, LZTS2, SIAH2, PNMA1, and TFCP2 were found to be highly enriched in the protein-protein interaction network. The significant cross talks were found in Hypertrophic cardiomyopathy, Small cell lung cancer, Proteasome, p53 signaling pathway, Arrhythmogenic right ventricular cardiomyopathy, Small cell lung cancer, SNARE interactions in vesicular transport, RIG-I-like receptor signaling pathway, and Hypertrophic cardiomyopathy pathways. The results offer new opportunities for target gene control in RA and OA cartilage destruction.

Connective tissue growth factor (CTGF) has been recently acknowledged as an ideal biomarker in the early disease course, participating in the pathogenesis of pannus formation in rheumatoid arthritis (RA). However, existing approaches for the detection of or antagonist targeting CTGF are either lacking or unsatisfactory in the diagnosis and treatment of RA. To address this, we synthesized and screened high-affinity single-stranded DNA aptamers targeting CTGF through a protein-based SELEX procedure. The structurally optimized variant AptW2-1-39-PEG was characterized thoroughly for its high-affinity (KD 7.86 nM), sensitivity (minimum protein binding concentration, 2 ng), specificity (negative binding to other biomarkers of RA), and stability (viability-maintaining duration in human serum, 48 h) properties using various biochemical and biophysical assays. Importantly, we showed the antiproliferative and antiangiogenic activities of the aptamers obtained using functional experiments and further verified the therapeutic effect of the aptamers on joint injury and inflammatory response in collagen-induced arthritis (CIA) mice, thus advancing this study into actual therapeutic application. Furthermore, we revealed that the binding within AptW2-1-39-PEG/CTGF was mediated by the thrombospondin 1 (TSP1) domain of CTGF using robust bioinformatics tools together with immunofluorescence. In conclusion, our results revealed a novel aptamer that holds promise as an additive or alternative approach for CTGF-targeting diagnostics and therapeutics for RA.

Chronic superficial keratitis (CSK) is a progressive inflammatory condition of the eye (cornea) that can cause discomfort and blindness. Differential disease risk across dog breeds strongly suggests that CSK has a genetic basis. In addition to genetic risk, the occurrence of CSK is exacerbated by exposure to ultraviolet light. Genome-wide association analysis considered 109 greyhounds, 70 with CSK and the remainder with normal phenotype at an age over four years. Three co-located variants on CFA18 near the 5′ region of the Epidermal Growth Factor Receptor (EGFR) gene were associated with genome-wide significance after multiple-test correction (BICF2P579527, CFA18: 6,068,508, praw = 1.77 × 10−7, pgenome = 0.017; BICF2P1310662, CFA18: 6,077,388, praw = 4.09 × 10−7, pgenome = 0.040; BICF2P160719, CFA18: 6,087,347, praw = 4.09 × 10−7, pgenome = 0.040) (canFam4)). Of the top 10 associated markers, eight were co-located with the significantly associated markers on CFA18. The associated haplotype on CFA18 is protective for the CSK condition. EGFR is known to play a role in corneal healing, where it initiates differentiation and proliferation of epithelial cells that in turn signal the involvement of stromal keratocytes to commence apoptosis. Further validation of the putative functional variants is required prior to their use in genetic testing for breeding programs.

PURPOSE To describe the histopathological characteristics of limbal stem cell deficiency (LSCD) due to chronic vernal keratoconjunctivitis (VKC). METHODS This retrospective study included 14 eyes of 13 patients who underwent simple limbal epithelial transplantation for total LSCD from 2017 to 2018. The histological characteristics of the excised fibrovascular pannus were compared between 2 groups of 7 eyes, each with LSCD due to VKC and chemical burns (CB). Histological characteristics and type of inflammation were studied using special stains and immunohistochemistry. Fisher exact test was used to detect the statistical significance of the histological differences between both groups. RESULTS Epithelial hypertrophy, epithelial downgrowth, and eosinophilic infiltration were noted in all eyes in the VKC group (7/7, 100%). Epithelial hypertrophy was noted in 3 of the 7 (42.8%) eyes in the CB group, whereas epithelial downgrowth and eosinophilic infiltrates were absent. The average chronic inflammatory score of the pannus (5.28) was higher in VKC than in CB (3.85; P = 0.1080). The presence of goblet cells was higher in the CB group (5/7, 1.4%) than in the VKC group (3/4, 2.8%), although not statistically significant. Other histological differences between the groups were not statistically significant. CONCLUSIONS The histopathological features of LSCD in VKC reveal some distinctive characteristics. These include the presence of epithelial downgrowth, eosinophilic infiltration, and epithelial solid and cystic implants. Although this information may be used to establish the diagnostic criteria for VKC as the cause of LSCD, further studies are needed to elucidate the reasons behind these unique findings.

Agonists and antagonists of the canonical Wnt signaling pathway are modulators of pathological aspects of rheumatoid arthritis (RA). Their activity is primarily modifying bone loss and bone formation, as shown in animal models of RA. More recently, modulation of Wnt signaling by the antagonist Sclerostin has also been shown to influence soft-tissue-associated inflammatory aspects of the disease pointing towards a role of Wnt signaling in soft-tissue inflammation as well. Yet, nothing is known experimentally about the role of Wnt ligands in RA. Here we provide evidence that altering Wnt signaling at the level of a ligand affects all aspects of the rheumatoid arthritic disease. WNT9a levels are increased in the pannus tissue of RA patients, and stimulation of synovial fibroblasts (SFB) with tumor necrosis factor (TNF) leads to increased transcription of Wnt9a. Loss of Wnt9a in a chronic TNF-dependent RA mouse model results in an aggravation of disease progression with enhanced pannus formation and joint destruction. Yet, loss of its activity in the acute K/BxN serum-transfer induced arthritis (STIA) mouse model, which is independent of TNF signaling, has no effect on disease severity or progression. Thus, suggesting a specific role for WNT9a in TNF-triggered RA. In synovial fibroblasts, WNT9a can activate the canonical Wnt/β-catenin pathway, but it can also activate P38- and downregulate NFκB signaling. Based on in vitro data, we propose that loss of Wnt9a creates a slight proinflammatory and procatabolic environment that boosts the TNF-mediated inflammatory response.

The coexistence of pannus and thrombus is not uncommon. Accurate diagnosis of the etiology of prosthetic valve dysfunction (PVD) is of utmost importance in guiding adequate and rational therapy. We present a case of PVD in which computed tomography played a decisive role in guiding treatment. (Level of Difficulty: Intermediate.), Central Illustration

Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by the failure of spontaneous resolution of inflammation with lifetime perseverance, becoming one of the major causes of disability in millions of people. It is mainly characterized by progressive erosion of cartilage in response to the formation of pannus leading to chronic polyarthritis and joint distortion. Early diagnosis and advances in molecular biology undoubtedly revolutionized therapeutic interventions in the past decade for better disease management. Despite favorable prospects, many patients still fail to respond to the current therapies urging a burning need to develop newer and safer medications. Herbal plants have been utilized since the ancient era and provided the base for massive bioactive compounds with flaunting therapeutic potential, many being advanced to drugs that are consumed worldwide for treating countless ailments. Scientific studies showed the involvement of several cellular mechanisms like oxidative stress suppression, downregulated synthesis of proinflammatory cytokines namely interleukins (IL-1, IL-6), TNF-α, NF-κB, demoted metalloproteinases induced cartilage destruction and augmentation of free radical scavenging and antioxidant activity in the treatment of rheumatoid arthritis. A plethora of active phytoconstituents like flavonoids, saponins, terpenes, alkaloids, lactones, etc, have been isolated from herbal plants with proven curative actions. The present review enlists some of the herbal drugs that can be used to amend the effects of rheumatoid arthritis and impart symptomatic relief to patients.

According to the World Health Organization, corneal blindness is the fourth most common cause of blindness and visual impairment worldwide. In Russia, up to 18% of blindness is caused by corneal damage. Limbal stem cell deficiency (LSCD) is one of the causes of corneal blindness and visual impairment due to anterior epithelial replacement with fibrovascular pannus. Bilateral LSCD may develop in patients with aniridia, Steven-Jones syndrome, and severe corneal burns of both eyes, leading to severe decrease in visual acuity in both eyes and, as a consequence, physical disability associated with blindness. In such cases, cell therapy, based on autologous oral epithelial culture as an alternative to allogeneic limbus transplants, is proposed for reconstruction of the anterior corneal epithelium. This new treatment method promotes corneal reepithelization, better visual acuity, reduced nonspecific ocular complaints and improved quality of life of patients. The effectiveness and significant increase in the frequency of transparent engraftment of donor corneas after cell therapy drives huge interest in this topic all over the world. This review presents literature data on the features of histotopography and methods for obtaining a cultured autologous oral mucosal epithelium, on cell markers that are used to identify epithelial cells, and on methods for creating cell grafts for subsequent transplantation to the corneal surface in LSCD patients.

A variety of conditions can lead to left ventricle outflow tract obstruction, but cases of subaortic stenosis decades following a mitral valve replacement are exceedingly rare. Any abnormal positioning of a prosthetic valve can result in continuous turbulence leading to permanent deposition of fibrous tissue. We present a case of a 56-year-old female that underwent mechanical mitral valve replacement, due to severe rheumatic mitral valve disease, with recurrent admissions for dyspnea. Ultimately, she underwent a left heart catheterization and during pullback from the left ventricle to the aorta a 100-mmHg pressure gradient was noted below the level of the aortic valve suggestive of subaortic stenosis. The subaortic stenosis was found to be secondary to pannus formation from her mitral valve prosthesis placed over twenty years ago.

Background Synovial sepsis is a frequent cause of morbidity and mortality in horses. Despite advances in diagnostics and treatments, persistent infection or chronic lameness can occur. Objectives To perform a scoping review to identify and evaluate the current evidence on factors implicated in the success of treatment for synovial sepsis. Study design Joanna Briggs Institute scoping review. Methods A protocol was registered and a systematic literature search was performed on CAB abstracts, Medline, Scopus and Embase. Inclusion and exclusion criteria were developed and studies systematically reviewed against this. Studies relating to factors affecting treatment success following synovial sepsis were retained and data was extracted on study method, population characteristics and factors significantly associated with treatment outcome. Results In total, 2338 studies were identified, and 61 were included to full paper analysis. Eight papers reported significant factors, identifying 15 risk factors associated with two measurements of outcome, either survival and/or return to athletic function. The 15 factors were identified and categorised into pre-, intra- and post-operative factors. Risk factors that were identified included the number or type of synovial structures involved, the presence of pannus, tendon and bone pathology, and the use of systemic antimicrobials. There were many discrepancies in inclusion criteria of cases of synovial sepsis as well as measurement and description of outcome variables. Main limitations Non-English language studies or conference proceedings were not included. Only small numbers of papers had similar findings. Conclusions Standardisation of inclusion criteria is essential to enable comparisons and analysis between studies on synovial sepsis. Future studies should use methodologies to reduce bias including multicentre and multinational studies, prospective study design, and robust statistical modelling.

The aim of this analysis was to re-examine the classical concept of distal interphalangeal joint (DIP) psoriatic arthritis (PsA) as an entheseal-driven disease. Two cadaveric fingers with severe psoriatic arthritis were analyzed. Our results demonstrate that inflammation of DIP PsA is multifocal without interconnection between entheses and articular cartilage of the DIP. We found a clear association between synovitis and focal loss of articular cartilage at the head of the intermediate phalanx. By contrast, the articular cartilage adjacent to the zone of severe enthesitis did not show notable damage. Fibrocartilaginous destructions of enthesis were characterized by either a multifocal lymphocytic inflammation, accompanied by osteoclastic resorption, beginning on the interface between the uncalcified and calcified fibrocartilage and then extending into the bone or a subchondral bone inflammation which insidiously destroyed first the bone and then the fibrocartilage. Some sections well showed an inflammation either mild or prominent starting at the level of vascular foramina of flexor enthesis, with secondary invading into the interface between bone and enthesis. The different anatomic sites examined showed a slight predominance of CD8+ T cells over CD4+ T cells: 52% up to 63% for CD8+ T cells vs. to 36% up to 48% for CD4+ T cells. Sparse interspersed CD1a+cells and PS100+cells were also seen with a predominance of PS100+ cells on CD1a+ cells. CD20+ B cells, plasmocytes, neutrophils, and mastocytes were absent or rare. CD123 positive cells were not observed. In DIP PsA, 3 findings predominate: (1) cartilage invasion by the thin pannus offers a more rational explanation for the focal joint destruction than does inflammation of the enthesis which is independent from articular cartilage, (2) the thick ventral plate and to a lesser extend the thin dorsal plate constitute a barrier between the inflamed entheses and the articular cartilage, and (3) an unusual form of minute vascular foramen contributes to the early stage of enthesitis. This small study suggests that DIP PsA is a complex disease. It affects anatomical micro sites which, although close, are in fact relatively independent of each other. Further studies are needed to test this hypothesis.

Although mechanical valve obstruction is rare. It is a rather fatal complication. Pannus and thrombus are common in etiopathogenesis.

Neuropsychiatric manifestations are commonly seen in lupus and limb paresis is commonly due to noncompressive spinal etiology. Here, we report a case of a 50-year-old female with Jaccoud's arthropathy who had presented with quadriparesis for 3 months. She was diagnosed with lupus during her hospital stay. Her magnetic resonance imaging of the spine showed the presence of a soft-tissue mass in the cervical spine with atlantoaxial dislocation causing severe cord compression. This case highlights the importance of suspecting compressive myelopathy secondary either to infection or inflammation due to disease process in the cervical spine of patients with lupus, especially with Jaccoud's arthritis, presenting with weakness of limbs.

The abnormal growth of tissue, called pannus, is frequently found in patients who have an implanted prosthetic heart valve. Its growth is related to the valve dysfunction and disturbed blood flow in the aorta. We performed in vitro experiments to demonstrate the effects of pannus formation on hemodynamics and valvular function. The results showed that the opening angle of the heart valve changes depending on the size and shape of the pannus. The circular pannus decreased the maximum opening angle of the heart valve. Although the opening motion of the valve was not affected by the semi-circular pannus, one of the valve leaflets obstructed by the semi-circular pannus had a closing dysfunction during the cardiac cycle, implying aortic insufficiency and regurgitation in the patients with this type of pannus formation. The experimentally measured pressure gradient and velocity-based transvalvular pressure gradient estimation increased with the growth of the pannus, although a discrepancy between the two estimations was observed.

Rheumatoid arthritis is known as a highly prevalent disease worldwide, often resulting in stable loss of capacity for work or complete disability over short period from the onset. Detected changes in the joint morphology may depend on the basic treatment received as well as depend on the level of control over the disease progression. The aim of this work is to study the diagnostic potential of Doppler ultrasound technique and Dopplerography in assessing the severity of changes in the knee joints depending on the received basic treatment and the level of control over disease in patients with rheumatoid arthritis. Correlation analysis carried out to compare the severity of bone erosions' indicators and the level of C-reactive protein has revealed no significant correlations. At the same time, there has been found a strong correlation between the level of C-reactive protein values and the blood circulation rate in the arteries of the pannus in all studied groups at the beginning of treatment and in 6 months of the therapy (r≥0.65, p≤0.03). The obtained results clearly demonstrate the effectiveness of the ultrasound diagnostics, especially Doppler indicators, in assessing the effectiveness of the basic treatment for patients with rheumatoid arthritis.

Although mechanical valve obstruction is rare. It is a rather fatal complication. Pannus and thrombus are common in etiopathogenesis.

Background. Charcot arthropathy is a serious medical and social problem. Histological studies of foot joints components in Charcot arthropathy complicated by osteomyelitis are few. The purpose of this study was to assess structural changes in the articular cartilage and subchondral bone of the foot joints in Charcot arthropathy complicated by osteomyelitis. Materials and Methods. The bone-cartilage fragments of the ankle, subtalar and metatarsophalangeal joints with the surrounding soft tissues of 20 patients with Charcot arthropathy complicated by chronic osteomyelitis were examined. Part of the material was fixed in neutral formalin. All samples were subjected to standard histological processing. Paraffin sections were stained by Masson’s tricolor method, hematoxylin and eosin. Part of the material was embedded in epoxy resins. Then semi-thin sections were stained with methylene blue and basic fuchsin. Histological preparations were studied by digitizing images under the AxioScope A1 microscope (Carl Zeiss MicroImaging GmbH, Germany).The phase of chronic osteomyelitis inflammation was assessed semi-quantitatively using the histopathological scale by A. Tiemann et al. (2014). Results. In 80% of the patients, the inflammatory phase of chronic osteomyelitis was characterized as active and subacute. In all cases, the areas with full-layer of articular cartilage unweaving, up to the subchondral zone, with cartilaginous tissue fragments rejection into the joint cavity were revealed. Cytoarchitectonics was disrupted. The main part of chondrocytes was in a state of destruction. The articular surface was covered with pannus. There were no basophilic line and the zone of calcified cartilage. The hyaline cartilage was replaced by granulation and/or fibrous tissue. An inflammatory infiltrates was noted in the superficial and deep areas of the cartilage. The impairment of the structure and/or complete absence of the subchondral bone due to the high activity of osteoclasts in the subchondral zone were revealed. An excessive amount of osteoclasts at the border with the articular cartilage was noted, while the signs of reparative bone formation were poorly expressed. Edema and thickening of the vascular walls of the microvasculature were recorded. Conclusion. The microscopic examination of the foot joints in Charcot arthropathy complicated by osteomyelitis revealed structural impairment and/or complete absence of the subchondral bone due to the high activity of osteoclasts in the subchondral zone. Structural changes in the subchondral bone and synovial pannus led to irreversible destruction of articular cartilage and the penetration of infection. These should be taken into account in surgical planning.

Rheumatoid arthritis (RA) is a progressive autoimmune inflammatory disease affecting 1% of the population with three times as many women as men. As many as 86% of patients suffering from RA have cervical spine involvement. Synovial inflammation in the cervical spine causes instability and injuries including atlantoaxial subluxation, retroodontoid pannus formation, cranial settling, and subaxial subluxation. While many patients with cervical spine involvement are asymptomatic, symptomatic patients often present with nonspecific symptoms resulting from inflammation and additional secondary symptoms that are due to compression of the brainstem, cranial nerves, vertebral artery, and spinal cord. Radiographs are the imaging modality used most often, while MRI and CT are used for assessment of neural element involvement and surgical planning. Multiple classification systems exist. Early diagnosis and treatment of cervical spine involvement is critical. Surgical management is indicated when patients experience symptoms from cervical involvement that result in biomechanical instability and, or a neurological deficit. Atlantoaxial instability managed with atlantoaxial fusion, retroodontoid pannus with neural element compression is managed with posterior decompression and atlantoaxial fusion or occipitocervical fusion. Cranial settling is managed can be managed with anterior decompression and posterior fusion or with dorsal only approaches. Subaxial subluxation is managed with circumferential fusion or posterior only decompression and fusion. Patients with atlantoaxial instability have better functional and neurologic outcomes. RA patients have higher complication rates and more frequent need for revision surgery than the general population of spine surgery patients.

Background:This study aimed to evaluate the clinical and surgical characteristics of patients who required reoperation after mechanical mitral valve replacement (MVR).Methods:We retrospectively identified 204 consecutive patients who underwent reoperation after mechanical MVR between 2009 and 2018. Patients were categorized according the reason for reoperation (perivalvular leakage, thrombus formation, or pannus formation). The patients' medical and surgical records were studied carefully and the rates of in-hospital complications were calculated.Results:The mean age was 51±12 years and 44% of the patients were male. The reasons for reoperation were perivalvular leakage (117 patients), thrombus formation (35 patients), and pannus formation (52 patients). The most common positions for perivalvular leakage were at the 6–10 o'clock positions (proportions of ≥25% for each hour position). Most patients had an interval of >10 years between the original MVR and reoperation. The most common reoperation procedure was re-do MVR (157 patients), and 155 of these patients underwent concomitant cardiac procedures. There were 10 in-hospital deaths and 32 patients experienced complications. The 10-year survival rate was 82.2 ± 3.9% in general, and the group of lowest rate was patients with PVL (77.5 ± 5.2%). The independent risk factors were “male” (4.62, 95% CI 1.57–13.58, P = 0.005) and “Hb P = 0.029).Conclusion:Perivalvular leakage was the most common reason for reoperation after mechanical MVR, with a low survival rate in long term follow-up relatively.

BACKGROUND Patients with prosthetic heart valves (PHV) are at an increased risk of endocarditis and dysfunction. Knowledge about the etiology of dysfunction and extent of endocarditis can have distinct treatment implications. Echocardiography has limitations due to PHV-related artifacts. We hypothesized that computed tomography (CT) will have incremental value over echocardiography for evaluation of PHV abnormalities with surgical findings as the reference standard. METHODS Consecutive patients with PHV that had a reoperation for valve replacement, had a contrast chest CT and echocardiogram within 1 year of the reoperation, between 2010 and 2018 at a single academic center formed the study cohort. CTs and echocardiograms were assessed for potential etiologies of dysfunction (valve degeneration, pannus and thrombus); and for extent of endocarditis (vegetation, abscess, and pseudoaneurysm). RESULTS Seventy-three patients (65.8% male, mean age 62.1 ± 16.5 years) formed the study cohort. The indication for reoperation was PHV dysfunction in 51 and PHV endocarditis in 22. Compared to echocardiography, CT diagnosed the etiology of PHV dysfunction in 17 (33.3%) more patients (9 valve degeneration, 8 pannus). In the PHV endocarditis cohort, CT failed to detect one vegetation and one abscess, whereas echocardiography failed to detect 1 abscess. In combination, CT and echocardiography demonstrated all the vegetations and abscesses. CONCLUSION CT may provide superior characterization in comparison to echocardiography for the identification of the cause of prosthetic valve dysfunction, and complementary information to echocardiography for the evaluation of prosthetic valve endocarditis.

Increased permeability and growth (angiogenesis) of blood vessels play a key role in joint swelling and pannus formation in inflammatory arthritis, a family of diseases influenced by reproductive hormones. The hormone prolactin (PRL) protects against joint inflammation, pannus formation, and bone destruction in adjuvant-induced arthritis and these effects may involve its proteolytic conversion to vasoinhibin, a PRL fragment that inhibits angiogenesis and vasopermeability. Here, we show that the intra-articular injection of an adeno-associated virus type-2 (AAV2) vector encoding vasoinhibin reduced joint inflammation, the hyperplasia, vascular density, and vasopermeability of the pannus, and the loss of bone in mice subjected to antigen-induced arthritis. In agreement, the AAV2 vasoinhibin vector reduced the expression of proinflammatory cytokines (interleukin-1β, interleukin-6), an endothelial cell marker (platelet endothelial cell-adhesion molecule 1), and proangiogenic molecules [vascular endothelial growth factor (VEGF), VEGF receptor 2, and hypoxia-inducible factor 1α] in the arthritic joint. Also, vasoinhibin reduced the synovial vasopermeability induced by the intra-articular injection of VEGF in healthy mice. Finally, vasoinhibin signals by blocking the phosphorylation/activation of endothelial nitric oxide synthase (eNOS) at Ser1179 and the AAV2 vasoinhibin vector inhibited the enhanced phosphorylation of eNOS Ser1179 in the arthritic joint. We conclude that vasoinhibin reduces joint inflammation and bone loss in arthritis by inhibiting pannus angiogenesis and vasopermeability via the blockage of VEGF-induced eNOS activation. These findings suggest the potential therapeutic benefit of AAV2-mediated vasoinhibin gene delivery in arthritis.

BACKGROUND: Bariatric surgery results in significant and durable weight loss and improved health in severely obese adolescents. An important adverse consequence of the massive weight loss after bariatric surgery is excess skin and soft tissue. The prevalence and clinical characteristics of excess-skin related symptoms have been described in adults undergoing bariatric surgery but not in adolescents. While the higher skin elasticity of adolescents may result in fewer excess skin problems compared to adults, this hypothesis remains untested. The purpose of the present study was to describe the natural history of excess skin and its associated complications among severely obese adolescents undergoing bariatric surgery. METHODS: We evaluated data from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, a prospective, multi-institutional study of adolescents (13-19 years) undergoing bariatric surgery. Abdominal pannus severity (graded 0-5) and excess skin symptoms were evaluated pre-operatively and for the first five years after bariatric surgery. RESULTS: Among the 217 study participants, 198 (90%) had an abdominal pannus and 16 (7%) reported pannus related symptoms at the time of bariatric surgery. Preoperative symptoms included intertriginous infections (n=12, 75%), recurrent cellulitis (n=5, 31%), and superficial cutaneous ulcerations (n=1, 6%). Participants with a higher pannus grade pre-operatively experienced both a greater reduction in pannus severity (p

Prosthetic valve thrombosis (PVT) is a life-threatening valve dysfunction. In asymptomatic cases, as well as certain symptomatic patients with PVT, the results of the first-line imaging tool, transthoracic echocardiography, may be inconclusive in terms of illustrating the thrombus, which is necessary in order to select the proper treatment option. Hence, a differential diagnosis based on clinical presentation may be challenging, and multimodality imaging, including echocardiography, cine fluoroscopy, and cardiac computed tomography, is usually required to distinguish between PVT and other prosthesis-related pathologies, such as pannus, vegetation, and prosthesis-patient mismatch.

Rheumatoid arthritis (RA) is a persistent autoimmune disease. Fibroblast-like synoviocytes (FLS) are a key component of invasive pannus and a pathogenetic mechanism in RA. Expression of bone morphogenetic protein 3 (BMP3) mRNA is reportedly decreased in the arthritic synovium. We previously showed that BMP3 expression is significantly downregulated in the synovial tissues of RA patients and models of adjuvant-induced arthritis (AIA). In the present study, we explored the association between BMP3 and FLS migration and secretion of proinflammatory factors in RA. We found that inhibition of BMP3 expression using BMP3 siRNA increased the proinflammatory chemokines and migration of FLS stimulated with TNF-α. Inhibition of BMP3 expression also increased expression of IL-6, IL-1β, IL-17A, CCL-2, CCL-3, VCAM-1, MMP-3, and MMP-9, but not TIMP-1, in AIA and RA FLS. Correspondingly, induction of BMP3 overexpression through intra-articular injection of ad-BMP3 diminished arthritis severity in AIA rats. We also found that BMP3 may inhibit activation of TGF-β1/Smad signaling. These data indicate that BMP3 may suppress the proliferation and migration of FLS via the TGF-β1/Smad signaling pathway.

Purpose Recently, intraoperative optical coherence tomography (iOCT) has evolved in the field of ophthalmic surgery. So far, the use of iOCT was mainly focused to lamellar keratoplasty, especially deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK). The aim of this study was to report our experiences with iOCT to introduce new possibilities of this application. Methods We used iOCT in 18 patients who underwent the following surgeries: DALK, DMEK, penetrating keratoplasty, autologous limbal transplantation, transscleral suture fixation of a posterior chamber lens, pannus removal on corneal surface and newborn investigation in Peters’ anomaly. We obtained qualitative video data for all procedures. Results With the iOCT, the cannula placement during DALK preparation of the recipient cornea and bubble formation could be visualized to improve the success rate of the big bubble injection. In DMEK, the iOCT enables the visualization of Descemet’s membrane removal in the recipient and graft orientation as well as better control of graft attachment. The iOCT enables intraoperative visualization of the graft–host interface during penetrating keratoplasty. During autologous limbal transplantation, transscleral suture fixation of a posterior chamber lens and removal of corneal surface pannus the iOCT is capable of showing the thickness of lamellar preparations to avoid penetrations and to save healthy recipient’s tissue. Conclusion The iOCT is a helpful device for intraoperative anterior segment imaging not only for DALK and DMEK. It is also beneficial in penetrating keratoplasty and every other form of lamellar preparation during corneoscleral surgery.

Objective To assess the value of real-time three-dimensional transoesophageal echocardiography (RT-3DTEE) in the diagnosis of pannus of prosthetic aortic valve. Methods A total of 89 patients with valve obstruction after receiving aortic valve replacement in our hospital were recruited between September, 2017 and September, 2019. All the patients underwent a second valve replacement, and the data of transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) and RT-3DTEE of these patients were analyzed. Results Of the 89 patients with valve obstruction, 51 were diagnosed to have pannus with a mean thickness of 6.5±1.1 mm in the prosthetic aortic valve as confirmed by pathological examination of the surgical specimen. The thickness of the pannus measured by RT-3DTEE, TTE and TEE were 6.2±1.2 mm, 5.1±1.2 mm, and 5.5±1.3 mm, respectively. The measurement by RT-3DTEE was well correlated with that on the surgical specimens (P < 0.01), and the correlation was significantly better that of TTE and TEE (P < 0.05). The thickness of the pannus measured by RT-3DTEE also differed significantly from that by TTE and TEE (P < 0.05). For the diagnosis of pannus, the sensitivity, specificity, positive predictive value and negative predictive value of RT-3DTEE were 84.3% 92.1%, 93.5% and 81.4%, respectively, significantly higher than those of TTE (41.1%, 89.5%, 84.0% and 53.1%, respectively) and TEE (64.1%, 89.5%, 89.2% and 64.4%, respectively; P < 0.05). The pannus detected by RT-3DTEE occurred most commonly in the right anterior quadrant, with a circumference of 18.4±5.2 mm, an area of 0.79±0.28 cm2, and a mean transaortic pressure gradient of 38±12 mmHg. The pannus area measured by RT-3DTEE was well correlated with the mean transaortic pressure gradient of the prosthetic valve; the degree of valve occlusion could be assessed based on the measured pannus area and the mean transaortic pressure gradient of the prosthetic aortic valve. Conclusion RT-3DTEE can improve the sensitivity and specificity of ultrasonic diagnosis of pannus in the prosthetic aortic valve and allows accurate evaluation of the degree of valve obstruction caused by the pannus, thus providing reliable evidence to facilitate the diagnosis and treatment of the condition.

Rheumatoid arthritis is the most prevalent systemic autoimmune disease in the world. It usually manifests as a symmetrical chronic polyarticular inflammation that affects the small and medium size, with the metacarpophalangeal joint, proximal interphalangeal, and the carpus being the most affected. There is atlanto-axoid joint involvement late in the course of the disease. The case is presented of an 80 year-old patient that debuted with cervical compression myelopathy due to the presence of pannus in the atlanto-axoid joint.

Introduction: Prosthetic heart valve thrombosis is a life-threatening complication after valve replacement surgery. Although subtherapeutic anticoagulation is the main cause, there are many other conventional and esoteric predisposing factors.Areas covered: The etiopathogenesis, diagnosis, and management of prosthetic heart valve thrombosis with particular focus on conventional and esoteric predisposing factors, diagnosis with multimodality imaging and current therapeutic approaches were covered.Expert opinion: Subtherapeutic anticoagulation remains the key driving force for the development of prosthetic valve thrombosis. However, cardiologists should be cognizant of other frequent or rare conventional and esoteric causes. The diagnosis is now more straightforward with the use of multimodality imaging. Transthoracic and transesophageal echocardiography with or without real-time three-dimensional imaging are the current gold standard modalities. Multidetector computed tomography is now a major complementary tool. The favorable clinical outcomes with recently introduced slow or ultra-slow infusions of alteplase, as compared to relatively poor surgical results, have rendered thrombolytic therapy the first-line treatment option in most eligible patients with prosthetic valve thrombosis. Surgical treatment could be reserved in whom thrombolytic therapy is contraindicated or has already failed. The efficacy and safety of thrombolytic therapy as compared to surgery should be confirmed with large observational cohorts, and ideally randomized trials.

Background: Rheumatoid spondylitis is a feature of long-lasting Rheumatoid Arthritis (RA), it presented by neck pain, headache and sleep disturbance. Atlantoaxial Joint (AAJ) is the commonest joint which affected among the cervical spine in patients with RA. When it is involved, it can be associated with dangerous complications. Aim of Study: This study aimed to evaluate the efficacy of intra-articular steroid injection of inflamed AAJ in RA patients, on neck pain, headache and sleep quality as well as the pre and post injection MRI assessment. Patients and Methods: Sixty rheumatoid arthritis patients with inflamed AAJ were recruited to the study. Group 1 (AAJ injected group, n=30), received intraarticular atlantoaxial steroid injection, guided by fluoroscopy and Group 2 (control group, n=30), received systemic steroids. Both groups were assessed with: Visual Analogue Scale (VAS) for nocturnal neck pain, Headache and Pittsburgh Sleep Quality Index (PSQI) for sleep disturbances. Contrast enhanced MRI before and after intervention were done for all patients. Results: The injected AAJ group had significant improve-ment of nocturnal neck pain, headache and sleep disturbance during the three months’ interval follow-up, in comparison to the control group. The injected AAJ group had a statistically significant improvement in the MRI synovial enhancement, inflammatory pannus, fibrosis and bone marrow edema in comparison to control group. Conclusion: Intra-articular steroid injection of atlantoaxial joint is considered as an efficient therapeutic option in acute inflamed atlantoaxial joint of RA patients regarding clinical and radiological findings.

Abnormal accumulation of neutrophils in a subarticular bone usually raises the concern for osteomyelitis or septic arthritis, a disabling and potentially life-threatening medical condition. At the pathology department of a specialized orthopedic institute, we observed a distinct pattern of subarticular inflammation mimicking infection characterized by collections of neutrophils, macrophages, and fibrin in pseudocystic spaces of variable size and extent in the superficial subarticular bone not accompanied by granulation tissue or necrosis. We coined the term "inflammatory pseudoabscess" to describe these accumulations. From 1997-2015, we reported inflammatory pseudoabscesses in 157 primary arthroplasty/osteotomy specimens from 143 patients without penetrating trauma or hardware in the affected joint. The predominant gross and histologic features were those of destructive/inflammatory joint disease, including lymphoplasmacytic synovitis (95.3%), subchondral osseous chronic inflammation (80.3%), exudative synovitis (58.0%), synovial pannus (52.0%), and marginal erosions of articular cartilage and/or subarticular bone (43.3%). Clinical information was available in 137 (95.8%) patients, 107 (overall: 74.8%) of whom had preoperatively or postoperatively diagnosed inflammatory arthropathy, most commonly rheumatoid arthritis. The remaining 30 (overall: 21.0%) patients had no documented inflammatory disorders, but some had bilateral or multijoint arthropathy, hands/feet involvement, lymphoplasmacytic synovitis, ulcerative colitis, or family history of inflammatory arthropathy. There was no documented infection-associated implant failure. We believe that inflammatory pseudoabscess represents an intraosseous manifestation of noninfectious inflammatory disorders of joints. This feature should be recognized by pathologists and used to suggest further clinical evaluation for undiagnosed inflammatory joint diseases.

Purpose To characterize the clinical presentation of limbal stem cell deficiency (LSCD) associated with glaucoma surgeries. Methods This is a retrospective cross-sectional study of patients with LSCD and glaucoma who presented to the Stein Eye Institute at the University of California, Los Angeles, between 2009 and 2018. Patients who underwent trabeculectomy and/or aqueous shunt surgery were included. The severity of LSCD was staged using global consensus guidelines and a clinical scoring system, and basal epithelial cell density was measured by in vivo confocal microscopy. Anatomic locations of glaucoma and non-glaucoma surgeries, locations of LSCD, and severity of LSCD were compared. Results Fifty-one eyes of 41 patients with LSCD associated with glaucoma surgery were included in this study. LSCD in these patients uniquely featured sectoral replacement of corneal epithelium by conjunctival epithelium, without corneal neovascularization or pannus. The sites of glaucoma surgery strongly correlated with the locations of LSCD (P = 0.002). There was a trend toward increased severity of LSCD in eyes with 2 or more glaucoma surgeries as compared to eyes with 1 glaucoma surgery, although the difference did not reach statistical significance (P = 0.3). Use of topical glaucoma medications correlated with LSCD severity, while the impact of antimetabolites did not reach statistical significance. The location of glaucoma drainage surgery is correlated with the location of LSCD. Conclusions LSCD associated with glaucoma surgery has clinical features distinct from LSCD resulting from other etiologies. Further study is required to delineate the full impact of glaucoma surgery on limbal stem cell function and survival.

Background This study aimed to confirm the safety and feasibility of simple pannus removal in patients with mechanical aortic valve dysfunction for pannus overgrowth by evaluating its early clinical outcomes. Methods From March 2015 to April 2019, 24 consecutive patients with mechanical aortic valve dysfunction due to subaortic pannus underwent reoperation. In 12 patients the repeat aortic valve replacement (AVR) was performed, and 12 received the simple pannus removal to preserve the previously implanted prosthesis. Results There was only 1 in-hospital death in simple pannus removal group. Significant differences were obtained between procedures in cardiopulmonary bypass (CPB) and aortic cross-clamp time (128.7 vs 179.7 and 74.2 vs 132.7 mins, respectively, P P > 0.05) in echocardiography 1 week after operation. In addition, the aortic transvalvular peak velocity and TMPG in echocardiography 1 week after operation in pannus removal group between the repeat and initial surgery were not statistically significant (2.6 ± 0.4 vs. 2.5 ± 0.3 m/s, 13.2 ± 3.6 vs. 13.0 ± 3.5 mmHg, P > 0.05). Conclusions Simple pannus removal was a safe and effective procedure with satisfied early clinical outcomes for pannus overgrowth in mechanical aortic valve. However, further randomized and long-term follow-up studies were warranted to determine the clinical effects of the simple aortic pannus removal.

Three-dimensional (3D) co-culture models have closer physiological cell composition and behavior than traditional 2D culture. They exhibit pharmacological effects like in vivo responses, and therefore serve as a high-throughput drug screening model to evaluate drug efficacy and safety in vitro. In this study, we created a 3D co-culture environment to mimic pathological characteristics of rheumatoid arthritis (RA) pannus tissue. 3D scaffold was constructed by bioprinting technology with synovial fibroblasts (MH7A), vascular endothelial cells (EA.hy 926) and gelatin/alginate hydrogels. Cell viability was observed during 7-day culture and the proliferation rate of co-culture cells showed a stable increase stage. Cell-cell interactions were evaluated in the 3D printed scaffold and we found that spheroid size increased with time. TNF-α stimulated MH7A and EA.hy 926 in 3D pannus model showed higher vascular endothelial growth factor (VEGF) and angiopoietin (ANG) protein expression over time. For drug validation, methotrexate (MTX) was used to examine inhibition effects of angiogenesis in 3D pannus co-culture model. In conclusion, this 3D co-culture pannus model with biological characteristics may help the development of anti-RA drug research.

Background Juvenile Idiopathic Arthritis (JIA) is a chronic disease characterized by prolonged synovial inflammation that may cause structural joint damage. However, little is known about cervical spine involvement in JIA. The main objective of this study is to describe radiological findings of the cervical spine in patients with JIA. Methods We conduct a retrospective monocentric study. All JIA patients were included (ILAR criteria). Sociodemographic, JIA subtype, and clinical characteristics were collected. Disease activity at JIA diagnosis was evaluated by JADAS10 (Juvenile Arthritis Disease Activity Score) in poly and oligoarticular subtypes and by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) in arthritis-related enthesitis form. Cervical spine radiographs including anteroposterior and lateral with flexion views were analyzed. A p-value < 0.05 was considered significant. Results We included 25 patients (16 girls and 9 boys) diagnosed with JIA with a mean age at disease onset of 9.9 ± 3.9 [3–16]. The median disease duration was 36 months (IQR 25–75%; 30–84). The JIA subtypes were in decreasing order of frequency: Enthesitis-related Arthritis (n = 9), Oligoarticular (n = 6), Polyarticular RF- (n = 4), Polyarticular RF + (n = 2), Systemic (n = 2), Psoriatic Arthritis (n = 1), and Undifferentiated (n = 1). Median ESR and CRP were 17 mm/h [2–98] and 15.4 mg/l [0–56] respectively. The Median BASDAI score was 2.8 [1–6.3]. Median JADAS10 score was 5.3 [0–20]. Four patients (16%) were on long-term corticosteroid therapy. Five patients (20 %) have a cervical spine involvement with the following subtypes: Polyarticular (n = 2), enthesitisenthesitis-related arthritis (n = 2), and systemic (n = 1). Clinical manifestations were neck pain (n = 3) and limited range of motion (n = 4). Neurological examination noted brisk deep tendon reflexes (n = 6), positive Babinski reflex (n = 1) and positive Hoffmann reflex (n = 2). No patient had a neurological deficit. The conventional radiographs of the cervical spine showed: loss of cervical lordosis (n = 2), diastasis C1-C2 (n = 3), erosion of the odontoid process (n = 1), and anterior ankylosis (n = 3). Subsequent cervical spine MRI confirmed these findings and showed pannus at the craniocervical junction in one case and block vertebra of C6-C7 in another case. Atlanto-axial subluxation was anteroposterior in 3 patients and rotatory in one. Conclusion Cervical spine involvement is frequent and underestimated in JIA, and its radiological features are various. Hence, regular radiographic monitoring of the cervical spine is required to prevent the development of this complication.

To the Editor, We have recently read with great interest the article by Wei et al. entitled “Recurrent prosthetic valve dysfunction in a patient with idiopathic hypereosinophilic syndrome: A case report and literature review”1 We appreciate the authors for the management of therapy in a patient with recurrent prosthetic valve dysfunction. On the other hand, we believe that there are some major drawbacks that need to be addressed. 2-s2.0-85117320228

Synovial fibroblasts (SFs) are specialized cells of the synovium that provide nutrients and lubricants for the maintenance of proper function of diarthrodial joints. Chronic TNF signals are known to trigger activation of SFs and orchestration of arthritic pathology via proinflammatory effector functions, secretion of cartilage degrading proteases and promotion of osteolysis. We performed single-cell (sc) profiling of SF’s transcriptome by RNA-sequencing (scRNA-seq) and of chromatin accessibility by scATAC-seq in normal mouse SFs and SFs derived from early and advanced TNF-driven arthritic disease. We describe here distinct subsets of SFs in the homeostatic synovium, serving diverse functions such as chondro- and osteogenesis, tissue repair and immune regulation. Strikingly, development of spontaneous arthritis by transgenic TNF overexpression primes the emergence of distinct pathology-associated SF subtypes. We reveal 7 constitutive and 2 disease-specific SF subtypes. The latter emerge in the early stage, expand in late disease and are localized in areas at the interface between the invasive pannus and the articular bone. The associated transcription profiles are characterized by enhanced inflammatory responses, promigratory behaviour, neovascularization and collagen metabolic processes. Temporal reconstruction of transcriptomic events indicated which specific sublining cells may function as progenitors at the root of trajectories leading to intermediate subpopulations and culminating to a destructive lining inflammatory identity. Integrated analysis of chromatin accessibility and transcription changes revealed key transcription factors such as Bach and Runx1 to drive arthritogenesis. Parallel analysis of human arthritic SF data showed highly conserved core regulatory and transcriptional programs between the two species. Therefore, our study dissects the dynamic SF landscape in TNF-mediated arthritis and sets the stage for future investigations that might address the functions of specific SF subpopulations to understand joint pathophysiology and combat chronic inflammatory and destructive arthritic diseases.

Prosthetic heart valve (PHV) dysfunction is an uncommon but potentially life-threatening condition. In routine practice, transthoracic echocardiography and cinefluoroscopy comprise first-line imaging for the diagnostic evaluation of PHV dysfunction. In cases in which the findings of echocardiography and cinefluoroscopy remain inconclusive or are contradictory, CT angiography can resolve these conflicts. CT angiography also provides incremental diagnostic information about patients with suspected PHV obstruction and endocarditis, in which case it can demonstrate the anatomic substrate and extent of involvement. Additionally, information regarding the coronary arteries, cardiac dimensions, and retrosternal space may be obtained in cases in which repeat surgery is planned. This imaging essay describes the imaging spectrum of valvular and paravalvular complications of PHV at CT angiography and how the knowledge regarding the spectrum of complications can be incorporated into multimodality imaging for guiding clinical management. Keywords: Prosthetic Heart Valve Dysfunction, Prosthetic Heart Valve Thrombosis, Pannus, Paravalvular Leak, CT Angiography, Cardiac, Valves Supplemental material is available for this article. © RSNA, 2021

Rheumatoid arthritis (RA) is a common, chronic, systemic autoimmune disease, and its clinical features are the proliferation of joint synovial tissue, the formation of pannus and the destruction of cartilage. The global incidence of RA is about 1%, and it is more common in women. The basic feature of RA is the body’s immune system disorders, in which autoreactive CD4+T cells, pathogenic B cells, M1 macrophages, inflammatory cytokines, chemokines and autoantibodies abnormally increase in the body of RA patients B cell depletion therapy has well proved the important role of B cells in the pathogenesis of RA, and the treatment of RA with B cells as a target has also been paid more and more attention. Although the inflammatory indicators in RA patients receiving B-cell depletion therapy have been significantly improved, the risk of infection and cancer has also increased, which suggests that we need to deplete pathogenic B cells instead of all B cells. However, at present we cannot distinguish between pathogenic B cells and protective B cells in RA patients. In this review, we explore fresh perspectives upon the roles of B cells in the occurrence, development and treatment of RA.

Background Porcine valves are used for mitral valve replacement, but the limited long-term durability has restricted the application in younger patients. Degenerated porcine mitral valves were explanted to analyze the failure modes and damage characteristics. Methods Twelve porcine valves were explanted via secondary mitral valve replacement surgery. Microcomputed tomography scanning, morphological and pathological examinations were performed to classify the cusp tears, calcification, and pannus formation. The causes of valve deterioration were subsequently analyzed. Results The mean age at first implantation was 45.42±19.58 years (range, 11-64 years). The mean duration of implantation was 9.39±4.14 years (range, 4.25-18.75 years). The indications for first surgery were rheumatic heart disease in 8 patients (66.67%), infective endocarditis in 2 patients (16.67%), degenerative valvular disease in one patient (8.33%), and congenital heart disease in one patient (8.33%). Type I cusp tears and commissural dehiscence that occurred near the stent post position were found in 6 (50%) and 5 (41.67%) valves, respectively. Calcification was detected in 6 (50%) cases, and pannus was found in most valves (91.67%). Conclusions Leaflet damage occurred near the stent posts area was the main failure mode of porcine mitral valves in this study. Patients who undergo the first surgery at younger age, the higher prevalence rate of rheumatic heart disease, the structure of bioprosthetic porcine valve, and left ventricular stresses could be considered as the main factors causing valve deterioration.

We report the case of a 72-year-old female patient admitted for worsening heart failure. The patient had undergone aortic valve replacement with a mechanical prosthesis 28 years before and since then she had several acute heart failure episodes, with a progressive increase in transprosthetic gradients, without identifying a specific cause.We describe the diagnostic tools used to reach a diagnosis, with particular emphasis on the use of cine-fluoroscopy that allowed to make the decisively diagnosis of prosthetic valve dysfunction, subsequently confirmed by cardiac computed tomography (CT). By cine-fluoroscopy, a widespread, easy, low-cost, and safe tool (no need for medium contrast and low radiation dose), it is possible to precisely define the function of the valve leaflets and measure their opening and closing angles, comparing them to the specific reference angles. To make the correct diagnosis we also performed a cardiac CT demonstrating a sub-aortic fibrous pannus. However, although cardiac CT is highly accurate for the identification of valve leaflet neoformations and abnormalities and for the discrimination between thrombotic formations and fibrous pannus, it is burdened by high costs, use of contrast medium, and limited available dedicated devices.

Spinal cord injury (SCI), particularly of the traumatic variety, is a relatively common condition that disproportionately affects the elderly. Cases of SCI with nontraumatic etiologies in the geriatric population have increased over the last 20 years, however. Pannus formation, resulting from chronic inflammation of the spine, is one such etiology that may progress to SCI and potentially result in rapid neurological degeneration. Here we describe a case of an elderly woman who presented with a sudden onset of quadriplegia without a history of trauma. Radiography revealed upper cervical instability and fracture due to the presence of a large erosive pannus formation. Unfortunately, in the context of severe SCI, the reversibility of neurological decline is not always guaranteed. Additionally, surgical intervention is not always appropriate, especially among the elderly population, where medical management and end-of-life care are more often delivered.

Background: Osteoarthritis (OA) is a common degenerative joint disease. Intra-articular injection of microcrystalline corticosteroid and platelet- rich plasma (PRP) are used for pain relief of knee OA.Aim of the Study: the goal of this study was to assess the possible therapeutic effects of corticosteroid compared to PRP in a rat model of induced OA.Material and Methods: Intra-articular injection of monosodium iodoacetate (MIA) was used for induction of OA in rats. Blood was collected from12 adult male rats for PRP preparation. 54 adult female albino rats were divided into control groups, OA model group and treated groups which received CS or PRP. All rats were euthanized after 28 days. Left knee joints were processed for histological examination by light microscope after staining by H& E, toluidine blue and masson’s trichrome stains. Right knee joints were grossly examined by stereomicroscope and scanning electron microscope (SEM). The obtained data were examined, further statistically analyzed and interpreted. Results: MIA caused gross anatomical and histological alterations in rat’s articular cartilage similar to human knee OA. Articular cartilage of corticosteroid and PRP treated knee joints showed thinning of the articular cartilage, fibrillation and presence of pannus- like tissue. These groups also showed significant increase in histopathological scores compared to the control group and OA model group in addition to gross macroscopic changes that were confirmed by SEM.Conclusion: This study showed that neither corticosteroid nor PRP could limit the structural changes in osteoarthritis and that different PRP preparation techniques have yielded varying results.

Background This study was conducted to evaluate the occurrence rate and risk factors of subaortic pannus (SAP) after bileaflet mechanical aortic valve (AV) replacement. Methods Between 1990 and 2014, 862 patients underwent primary AV replacement with bileaflet mechanical prosthesis. SAP was defined as (1) gradual increase in mean pressure gradient through mechanical AV without any evidence of motion limitation of the leaflets on echocardiography and (2) AV mean pressure gradient >40 mm Hg or AV peak velocity >4 m/s on echocardiography, and (3) any visible subaortic tissue ingrowth beneath the mechanical AV on echocardiography or computed tomography. Clinical and echocardiographic follow-up durations were 13.8 ± 8.0 and 10.7 ± 7.9 years, respectively. Results Mean age was 51.1 ± 12.1 years and concomitant surgeries were performed in 503 patients (58.4%). Overall survival at 10 and 20 years was 84.2 and 67.1%, respectively. SAP occurred in 33 patients, and in only 2 patients during the first 10 years after surgery. The cumulative incidence of SAP formation at 10, 20, and 25 years were 0.3, 5.0, and 9.9%, respectively. The Fine and Gray model demonstrated that small prosthetic valve size (hazard ratio [HR] [95% confidence interval, CI] = 0.738 [0.575–0.946]), young age (HR [95% CI] = 0.944 [0.909–0.981]), and concomitant mitral valve replacement (MVR) (HR [95% CI] = 3.863 [1.358–10.988]) were significant risk factors for the SAP formation. Conclusions SAP occurred gradually over time with 10- and 20-year cumulative incidence of 0.3 and 5.0%, respectively. Young age, small prosthetic valve size, and concomitant MVR were risk factors for SAP formation. Therefore, we recommend efforts to select large prostheses for young patients requiring concomitant MVR.