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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 (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.

Purpose: To compare the role of ultrasonography and MRI in the diagnosis of synovitis involving wrist and hand joints in Rheumatoid arthritis patients. Materials and methods: Fifty patients with rheumatoid arthritis involving the wrist were subjected to hand and wrist ultrasonography Doppler and MRI and the results are compared and correlated during the period from December 2015 to January 2017. Results: Ultrasound detected synovial hypertrophy (pannus) in 42 wrist joints while MRI detected it in 46. Power Doppler detected increased vascularity within 30 wrist joints (60%), MRI detected synovial enhancement within 38 (76%). Power Doppler detected synovial activity (vascularity) in MCP joints of 13 patients and MRI detected synovial activity (enhancement) in MCP joints of 9 patients. Ultrasound detected erosions in 35 wrist and 27 MCP joints and MRI detected erosions in 37 wrist and 25 MCP joints. Ultrasound detected tendinitis in 9 extensor tendons and MRI detected tendinitis in 8 tendons. Conclusion: We found a significant correlation between power Doppler ultrasonography and MRI in the detection of signs of inflammation and bone destruction in the wrist and hand joints in rheumatoid arthritis, which raise the potential importance of power Doppler study in the assessment and monitoring of disease activity as a reliable non-invasive method. Keywords: Rheumatoid artheritis, MRI, Ultrasonography

Background the sparsity of established tools for the grading of limbal stem cell deficiency hinder objective assessments of the clinical outcome of cultivated limbal epithelial cell transplantation. To advance towards the development of standards for the comparison of the outcomes of these bio-surgical protocols we have now applied a battery of recognized objective and patient-declared subjective outcome criteria to the autologous modality of cultivated limbal epithelial cell transplantation. Methods the prospective study involved ten patients (M/F = 9/1; mean age = 42.1 years) displaying overt unilateral limbal stem cell deficiency complying with the inclusion criteria described in Methods. Limbal biopsies were obtained from the contralateral eye and their outgrowths after 2-week cultures were transplanted on the affected eye after pannus resection. Outcomes were followed up for 12 months. the objective tests were scores for best-corrected visual acuity (BCVA); using the LogMAR scale, a multiparametric ocular surface score (OSS), and the Schirmer's test. Subjective scores were based on patient answers to a) perception of visual improvement/pain; b) the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25); and c) the 12-item Ocular Surface Disease Index Questionnaire (OSDI). All procedures were performed under good manufacture practices using solely xeno-free reagents. in all cases, a single biopsy was divided into two pieces and they were expanded in order to prevent outgrowth failure. in 5 patients, both biopsies generated healthy culture sheet. in those cases the lesser outgrowth were used for immune-histological characterization. Results the experimental parallel outgrowth samples showed a similar percent of p63 alpha(+)cells. PreOp and 12-month PostOp BCVAs and OSSs were, respectively, 1.15 +/- 0.70; 0.21 +/- 0.13 and 7.40 +/- 2.01; 2,30 +/- 1.30, (p < 0.05). Patient's responses to all three question sets except ocular pain were consistent with significant improvement (p < 0.05). Conclusion Objective clinical metrics demonstrate that in patients with limbal stem cell deficiency, cultivated limbal epithelial cell transplantation improves vision and ocular surface health and subjective visual perceptions., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [115S423]; USPHSUnited States Public Health Service [RO1-EY 029279, RO1-EY014878], OBS: the Scientific and Technological Research Council of Turkey (TUBITAK)(Project number:115S423); JMW: USPHS RO1-EY 029279 and RO1-EY014878.

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation, which forms pannus with bone destruction. Bony ankylosis is also observed following inflammation; however, the mechanism behind this aberrant bone formation in RA had remained unclear. Based on our recent findings obtained using a novel arthritis model called D1BC mouse, we found that synovial fibroblasts in pannus consist of at least three different populations with the osteochondrogenic lineage being predominant. We also found endochondral ossification like that in embryonic bone development adjacent to invasive synovial fibroblasts. Such ectopic endochondral ossification leads to the failure of bone repair and results in ankylosis. In this review, we describe the character of synovial fibroblasts toward the osteochondrogenic lineage and ectopic endochondral ossification in an inflammatory arthritis mouse model.

Background Mechanical aortic valve dysfunction is a rare but potentially fatal complication. It is usually caused by thrombosis, vegetation, and pannus overgrowth. However, it very rarely occurs immediately after the cardiopulmonary bypass weaning period. Case presentation We describe a case of stuck leaflet after the implantation of a mechanical aortic valve because of residual suture materials interfering with mechanical aortic valve leaflet closure, which is a very rare cause and has not been reported until now. Conclusion The residual suture materials for mechanical aortic valve replacement could cause mechanical valve dysfuction indicated as stuck leafet.

Although pannus is an important cause of prosthetic valve dysfunction, the minimum pannus size that can induce hemodynamic dysfunction has not yet been determined. This study investigated the correlation between the limitation of motion (LOM) of the prosthetic valve and pannus extent and determined the pannus extent that could induce severe aortic stenosis.This study included 49 patients who underwent mechanical aortic valve replacement (AVR) and showed pannus on cardiac computed tomography (CT). Pannus width, ratio of pannus width to valve diameter, pannus area, effective orifice area, encroachment ratio by pannus, pannus involvement angle and percent LOM of mechanical valves were evaluated on CT. Transvalvular peak velocity (TPV) and transvalvular pressure gradient (TPG) were measured by transesophageal echocardiography to determine the degree of aortic stenosis. The relationship between percent LOM of the prosthetic valve and pannus extent and the cut-off of pannus extent required to induce severe aortic stenosis were evaluated.The mean interval between AVR and pannus formation was 11 years and was longer in patients with than without severe aortic stenosis (14.0 vs. 7.3 years). On CT, the percent LOM of the prosthetic valve was significantly associated with the extent of pannus only in patients with pannus involvement angle 180° (r = 0.55-0.68, P 0.01). Pannus width, effective orifice area, and encroachment ratio were significantly associated with increased TPV and TPG (r = 0.51-0.62, P 0.01). Pannus width 3.5 mm, pannus width/valve inner diameter 0.15, and encroachment ratio 0.14 were significantly associated with severe aortic stenosis (TPV 4 m/s; mean TPG ≥ 35 mmHg), with c-indices of 0.74-079 (P 0.005).CT-derived pannus extent parameters are good indicators of significant hemodynamic changes with increased TPV and mean TPG.

Objective Cardiac masses comprise a category that includes benign, malignant, and nontumoral mass lesions. The present study aims to share the findings relating to cardiac masses observed at our tertiary cardiology hospital in Turkey. Methods The records of patients who presented with cardiac masses and underwent surgery at our institute between 2006 and 2015, and whose tissue samples were sent to a pathology laboratory, were retrospectively reviewed in a consecutive manner. Results The study included 228 patients with an average age of 52.5 ± 17.3 years. Of the study's subjects, 95 (41.7%) were male and 133 (58.3%) female. The most commonly observed mass was myxoma in 68 patients (29.8%), of whom 20 (29.4%) were male and 48 (70.6%) female. The second most frequently detected mass was pannus, with 38 cases (16.7%) - 10 (26.3%) in males and 28 (73.7%) in females. The third most common cardiac mass was thrombus (16.2%), with 18 cases of thrombi in men (48.6%) and 19 (51.4%) in women. Conclusion The most commonly observed cardiac mass was myxoma and most were localized in the left atrium. The second most frequently detected mass was pannus, which was mostly found on mitral mechanical prosthetic valves. Thrombi were the third most prevalent mass and were commonly localized in the right atrium.

The Chiari I malformation (CIM) is commonly encountered by neurosurgeons and can have different etiologies and clinical presentations. We report a CIM patient who presented with symptoms of ventral brain stem compression and was found to have a large peri-odontoid pannus. Posterior fossa decompression was performed with a planned second-stage odontoidectomy. However, at the 6-month follow-up, postoperative images demonstrated a mostly resolved pannus and improvement of the brain stem compression symptoms, and the patient progressed uneventfully without the need for odontoidectomy. This case illustrates the resolution of a significant and symptomatic peri-odontoid pannus in a patient with CIM without craniocervical fusion or odontoidectomy. Such a case indicates that not all peri-odontoid pannus formations in CIM patients are due to hypermobility at the craniocervical junction.

Background The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. Methods Fine needle aspiration biopsy of the sacroiliac joint (SIJ) was performed in 193 patients with axSpA. Clinical, laboratory, and imaging data were collected at baseline and during the follow up. Immunohistochemistry analysis was performed to detect CD34+ microvessels, CD68+ osteoclasts/macrophages, vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), and caspase-3. Autopsy subjects were used as controls. Results In early sacroiliitis (grade 0–1) all pathological features could be observed, with the most common being subchondral pannus formation. Among the 193 patients, 98 were followed up for 1–13 years (mean 3.6 years); 63.3% had radiological progression at the endpoint. Multiple regression analysis showed that cartilage pannus invasion (OR 2.99, P = 0.010) and endochondral ossification (OR 3.97, P = 0.049) at baseline were risk factors for radiological structural damage. Compared to SIJ controls, the subchondral microvessel density, number of CD68+ multinuclear osteoclasts, and the levels of VEGF, caspase-3, MMP-3, and TNF-α expressed at the interface of the bone and cartilage were significantly higher in patients with sacroiliitis. Conclusions Subchondral fibrovascular tissue formation is the most important pathological feature in early sacroiliitis. The existence of cartilage pannus invasion or endochondral ossification at baseline can predict radiological structural damage during the follow up. Electronic supplementary material The online version of this article (10.1186/s13075-018-1594-z) contains supplementary material, which is available to authorized users.

The clinical significance of pannus detected on computed tomography (CT) has not yet been investigated. The purposes of this study were to investigate the clinical significance of pannus detected on cardiac CT in patients who underwent aortic valve replacement (AVR) with mechanical valves, and to determine predictors for pannus severity. A total of 92 patients who underwent cardiac CT and TTE and who had undergone mechanical AVR were included. The geometric orifice area (GOA), the presence of limitation of motion (LOM) and pannus were evaluated on CT. The GOA, presence of LOM, and presence and severity of pannus were compared with echocardiographic parameters. Logistic regression analysis was performed to determine the predictors for pannus severity. The GOA on CT positively correlated with effective orifice area on TTE (r = 0.733, P

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune destructive arthropathy prevalent among people in the age group of 40–70 years. RA induces severe pain, swelling and stiffness of joints resulting in bone damage. RA leads to reduced life expectancy when left untreated. RA is characterized by synovial hyperplasia, infiltration of inflammatory cells resulting in formation of pannus. Synovial hyperplasia is mediated by proinflammatory cytokines, notably IL-1 and TNF-α. NF-κB is a predominant transcription factor in amplifying the inflammatory response. The translocation of activated NF-κB into the nucleus triggers the transcription of several genes that induce proinflammatory cytokine production. The inhibition of NF-κB translocation aids blocking the activation of proinflammatory cascades. The quest for more effective and side-effect free treatment for RA unveiled phytochemicals as efficacious and promising. Phytochemicals have been a source of therapeutic substances for many ailments from ancient times. Their therapeutic ability helps in developing potent and safe drugs targeting immune inflammatory diseases driven by NF-κB including RA. This review highlights the importance of NF-κB inflammatory cascade in RA so as to elucidate the crucial role of phytochemicals that inhibit the activity of NF-κB.

Background Haemodynamic performance of heart valve prosthesis can be defined as its ability to fully open and completely close during the cardiac cycle, neither overloading heart work nor damaging blood particles when passing through the valve. In this perspective, global and local flow parameters, valve dynamics and blood damage safety of the prosthesis, as well as their mutual interactions, have all to be accounted for when assessing the device functionality. Even though all these issues have been and continue to be widely investigated, they are not usually studied through an integrated approach yet, i.e. by analyzing them simultaneously and highlighting their connections. Results An in vitro test campaign of flow through a bileaflet mechanical heart valve (Sorin Slimline 25 mm) was performed in a suitably arranged pulsatile mock loop able to reproduce human systemic pressure and flow curves. The valve was placed in an elastic, transparent, and anatomically accurate model of healthy aorta, and tested under several pulsatile flow conditions. Global and local hydrodynamics measurements and leaflet dynamics were analysed focusing on correlations between flow characteristics and valve motion. The haemolysis index due to the valve was estimated according to a literature power law model and related to hydrodynamic conditions, and a correlation between the spatial distribution of experimental shear stress and pannus/thrombotic deposits on mechanical valves was suggested. As main and general result, this study validates the potential of the integrated strategy for performance assessment of any prosthetic valve thanks to its capability of highlighting the complex interaction between the different physical mechanisms that govern transvalvular haemodynamics. Conclusions We have defined an in vitro procedure for a comprehensive analysis of aortic valve prosthesis performance; the rationale for this study was the belief that a proper and overall characterization of the device should be based on the simultaneous measurement of all different quantities of interest for haemodynamic performance and the analysis of their mutual interactions. Electronic supplementary material The online version of this article (doi:10.1186/s12938-017-0314-2) contains supplementary material, which is available to authorized users.

To compare the role of fresh and dry preserved amniotic membrane transplantation (AMT) in partial limbal stem cell deficiency (LSCD). 30 Patients of partial LSCD involving

It is unclear when the synovial-based inflammatory process of gout begins. The aim of this study was to determine the percentage of patients with inter-critical gout who have chronic synovial-based inflammation as evidenced by synovial pannus on a contrast-enhanced magnetic resonance imaging (MRI) of their most involved joint and determine if the presence and/or severity correlates with their serum urate levels. All patients received a 3 T MRI of their index joint, serum urate level, CRP, and creatinine. The primary endpoint was to determine the prevalence of synovial pannus and the correlation of serum urate levels with the presence and/or severity of the synovial pannus on that same joint. MRI erosions, tophi, swelling, effusion, and osteitis were also documented. Seventy-two of 74 subjects (90 % men) completed the protocol. Fifty-three of 72 (74 %) index joints were the first metatarsophalangeal joint. Thirty-nine (54.2 %) of the patients were on urate-lowering therapy; 15 (20.8 %) and 7 (9.7 %) were taking colchicine or a NSAID daily, respectively. Of the 72 subjects, 63 (87.5 %) had synovial pannus on their MRI with good inter-reader agreement between the two radiologists. The mean serum urate level was 7.93 mg/dL. There was no correlation with the presence (p = 0.33) or severity (p = 0.34) of synovial pannus and serum urate levels. There was also no correlation with the presence or severity of synovial pannus and the secondary endpoints. The majority of patients with inter-critical gout have evidence of chronic synovial-based inflammation. However, the presence and severity of this inflammation do not appear to correlate with serum urate levels.

We evaluated the diagnostic usefulness of electrocardiographically gated multidetector-row computed tomography (MDCT) for prosthetic valve dysfunction (PVD) of an ATS valve. Twenty-four patients underwent MDCT following echocardiography and cineradiography. Echocardiography and cineradiography showed normal valve function in 17 patients and PVD in 7. PVD included aortic prosthetic valve obstruction in 4 patients, an aortic annular aneurysm with paraprosthetic regurgitation in one, and a blocked leaflet in the mitral position in 2. Among the 7 patients, 5 received reoperation after MDCT. MDCT revealed a subprosthetic mass in all 5 patients with PVD and in 4 patients with normal valve function in the aortic position. In addition to a subprosthetic mass, an annular aneurysm was found in one. Valvular masses were detected in 2 patients with mitral PVD. At reoperation, subprosthetic pannus in the aortic position was detected in 2 patients, subprosthetic pannus and annular aneurysm with paraprosthetic leaks in one, and mitral valve thrombosis in 2. These findings confirmed at reoperation matched to the findings observed on MDCT. The mean CT attenuation of the subprosthetic mass in 6 patients was 152 ± 12 HU and that of the subprosthetic pannus in 3 patients was 163 ± 17 HU. CT attenuation of the thrombus in the mitral valve in the 2 patients was 60 and 99 HU. Our study demonstrates that MDCT is a valuable and reliable diagnostic technique for PVD in an ATS valve and that MDCT may identify an abnormality causing PVD.

Synovial angiogenesis is a component of rheumatoid pannus and considered to be an important early step in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to evaluate the serum levels of angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), as well as the significance of the Ang2/Ang1 ratio in RA in relation to the joints’ blood flow signals and RA activity parameters. In addition, we studied their relevance in predicting the state of angiogenesis. This study was carried out on 65 consecutive very early RA patients. Power Doppler ultrasonography was performed in a total of 10 joints. The blood flow signals of each joint were scored on a three-grade scaling system. The total of the scores of the 10 joints was defined as the total signal score (TSS). On the same day, serum variables including vascular endothelial growth factor (VEGF), Ang1 and Ang2 levels, and clinical disease activity were evaluated. All the parameters measured were reassessed after 1 month. Serum VEGF, Ang2 levels, and Ang2/Ang1 ratio were significantly correlated with C-reactive protein, DAS28-CRP, and TSS at baseline and after 1 month. Moreover, significant correlations were observed between serum VEGF and Ang2 levels and Ang2/Ang1 ratio both at baseline and 1 month later. Interestingly, baseline serum VEGF level and Ang2/Ang1 ratio were significantly correlated with TSS after 1 month. Serum concentrations of VEGF and Ang2 as well as Ang2/Ang1 ratio were correlated with parameters of inflammation in early RA. Elevated serum VEGF and Ang2/Ang1 ratio (in favor of Ang2) could reflect a phase of vigorous angiogenesis.

Salvage panniculectomy is sometimes the only solution to remove a massive pannus or abdominal apron, which is the source of many physical, social, and emotional problems for the patient. Often, the panniculus morbidus prevents weight loss, as the patient cannot exercise and can lead to hygiene and chronic pain issues, including intertrigo, chronic infections, ulcerations, and low-back pains. The heavier the panniculus, the more marked the symptoms. Here, we present a case of a severely obese patient, with a large panniculus extending below the knees, accompanied by a large abdominal incisional hernia containing intestines. Recently, the patient’s lower abdomen became ischemic and infected, making the patient’s diabetes mellitus difficult to control. After a long ineffective period of local care and antibiotic therapy, the surgical removal was attempted. Surgery consisted resection of a 16-kg panniculus and incisional hernia repair with a resorbable mesh. Postoperative recovery was relatively simple. Patient’s quality of life showed a dramatic improvement, as well as the hygiene, toilet habits, and mobility. In this kind of patients, surgery can be technically difficult and carries significant postoperative risks, but it remains the only viable option for long-term survival.

A reliable assessment of the vascular perfusion of flaps in the postoperative period can be challenging. Clinical assessment of capillary refill is an integral component of this evaluation. Ten consecutive patients undergoing abdominoplasty were studied. The resected pannus was brought to the back table and assessed for capillary refill every 5 min. The time elapsed from complete resection until the last refill was observed and recorded. Our findings somewhat surprisingly show that capillary refill continues for an average of 75 min in an abdominoplasty specimen after its complete separation from its blood supply. We believe that capillary refill is testing the patency of the capillary microcirculation rather than the actual perfusion of the flap. This limits the value of capillary refill in the clinical evaluation of flaps. Level of Evidence: Level III, diagnostic study.

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

A artrite reumatoide (AR) e uma doenca autoimune, associada a sinovite poliarticular infl amatoria, que acomete principalmente as articulacoes perifericas. Cerca de 1% da populacao mundial e afetada, sendo duas a tres vezes mais prevalente em mulheres. Apresenta patogenese complexa e multifatorial. A sinovia das articulacoes afetadas e infi ltrada por linfocitos T e B, macrofagos e granulocitos. A sinovia reumatoide adquire caracteristicas proliferativas, formando o pannus, e invade a cartilagem articular e o osso, levando a destruicao da arquitetura normal da articulacao e a perda de funcao. A diminuicao da expressao de proteinas reguladoras do complemento (PCR) parece desempenhar papel importante na atividade da AR, associada ao agravamento dos sintomas clinicos. A superativacao do sistema complemento (SC) e a causa da exacerbacao da doenca em varios modelos de doencas autoimunes. O presente artigo tem por objetivo revisar os principais aspectos relacionados a regulacao do SC na AR, a fi m de propiciar melhor compreensao do potencial papel desse sistema na fi siopatologia e na atividade da doenca. Rheumatoid arthritis (RA) is an autoimmune disease associated with polyarticular infl ammatory synovitis affecting mainly peripheral joints. It affects approximately 1% of the world population, being two to three times more prevalent in women. Rheumatoid arthritis has a complex and multifactorial pathogenesis. The synovium of the affected joints is infi ltrated by T and B lymphocytes, macrophages, and granulocytes. The rheumatoid synovium has proliferative characteristics, forming the pannus, which invades cartilage and bone, leading to normal architecture destruction and function loss. The decreased expression of complement regulatory proteins (CRP) seems to play an important role in RA activity, and is associated with worsening of the clinical symptoms. In several models of autoimmune diseases, the overactivation of the complement system (CS) is the cause of disease exacerbation. This article aimed at reviewing the main aspects related to CS regulation in RA in order to provide a better understanding of the potential role of this system in the pathophysiology and activity of the disease.

Synovial mesenchymal cells, matrix metalloproteinases (MMPs), and osteoclasts are the three major players directly responsible for the pathogenesis of rheumatoid joint destruction. First, synovial mesenchymal cells, internally driven by a transcription factor c-Fos/AP-1, not only directly invade cartilage and bone as a granulation tissue called "pannus" but also release inflammatory cytokine interleukin (IL)-1β. IL-1β induces MMPs and activates osteoclasts. Synovial cells can also present antigen to T cells to drive antigen-specific immune responses. Second, cartilaginous joint matrix can only be degraded after the first attack of collagen fibrils by MMPs, and importantly, most of the MMPs are under the control of c-Fos/AP-1 and IL-1β as well. Third, differentiation of osteoclast is driven internally by NFATc1, where NFATc1 is under the control of TRAF6, c-Fos/AP-1 and osteoclastogenic signaling complex. IL-1β has been shown to induce osteoclastogenesis directly and also indirectly via signaling through RANKL. Therefore, IL-1β and c-Fos/AP-1 influence each other's gene expression and activity, resulting in an orchestrated cross-talk that is crucial to arthritic joint destruction, and thus, blockade of IL-1β and/or c-Fos/AP-1 can be most promising as a therapeutic target, and in fact, a selective inhibition of c-Fos/AP-1 does resolve arthritic joint destruction.

A 37-year-old female, who had undergone mitral valve replacement with a monoleaflet mechanical prosthesis for mitral stenosis in 1997, was admitted to outpatient clinic with exertional dyspnea and chest discomfort over preceding 3 months. Her physical examination revealed mildly muffled prosthetic valve sounds, pansystolic murmur on lower left sternal border, and bilateral fine rales at the bases of the lungs. Her electrocardiography showed atrial fibrillation. Transthoracic echocardiography revealed severe left ventricular outflow tract (LVOT) obstruction with mean gradient of 42 mmHg (Fig. 1a, c; Video 1) and severe tricuspid regurgitation. Two-dimensional transesophageal echocardiography (2D-TEE) showed stenosis of mechanical mitral valve (MMV) with pressure half-time (PHT) of 157 ms (PHT was 98 ms in the previous echocardiography) and mean gradient of 13 mmHg. Aortic valve function and leaflet motion of MMV were normal, but there was a hyperechogenic appearance at the ventricular side of the MMV. With the transducer array at 120 , 2D-TEE revealed that the hyperechogenic mass on the ventricular side of the MMV caused narrowing of the LVOT (Fig. 2a; Video 2). Real-time three-dimensional transesophageal echocardiography (RT-3D-TEE) clearly delineated an eccentric semicircular pannus overgrowth which was located anteriorly on the ventricular side of the MMV (Fig. 2b; Video 3), resulting in LVOT obstruction (Fig. 2c; Video 4). Redo mitral valve replacement with a bileaflet mechanical prosthesis (no. 29, St. Jude Medical) and concomitant repair of the tricuspid valve were performed, and anteriorly eccentric semicircular pannus tissue was removed from the left ventricular side of the mitral prosthesis (Fig. 2d). Postoperative transthoracic echocardiography (TTE) revealed normal functioning mitral prosthetic valve with normal LVOT gradients (Fig. 1b, d; Video 5). Prosthetic heart valve obstruction caused by pannus formation is an uncommon but serious complication. Determination of the precise etiology of valvular obstruction is essential, as this can have an impact on the course of surgical versus thrombolytic therapy [1]. Although 2DTEE is the first method of choice in the diagnostic algorithm, exact visualization of pannus is almost impossible [2]. However, RT-3D-TEE is a very useful imaging technique and permits differentiation of pannus overgrowth from other MMV pathologies [3, 4]. Herein, we present an anteriorly localized eccentric pannus overgrowth on the left ventricular side of MMV, which is an uncommon cause of LVOT obstruction.

Objective: To observe the effects of moxibustion therapy at Shenshu (BL 23) and Zusanli (ST 36) of rats with induced rheumatoid arthritis (RA) on the serumal intercellular cell adhesion molecule-1 (ICMA-1) and the pathological tissue, to discuss the mechanism of the warming and activating effect of moxibustion. Methods: After establishing the RA rats model, the induced rats were treated with moxibustion therapy on the acupoint Shenshu (BL 23) and Zusanli (ST 36), followed by analyzing the pathological section of the ankle of the hind limb and testing the ICAM-1 content with ELISA. Results: The plantar circumferences of the induced rat increased significantly compared with the rats in the control group (P

To clarify the relationship between clinical symptoms and histological status in patients with ocular cicatricial pemphigoid (OCP) and Stevens-Johnson syndrome (SJS). Clinical symptoms of four OCP and eight SJS patients in the chronic phase were scored with our recently proposed grading system. The histological status of the pannus tissue removed from the corneal surface during surgery was investigated using immunohistological techniques. All participants showed total loss of the palisades of Vogt and conjunctivalization of the entire corneal surface. All pannus tissues expressed the conjunctival epithelium marker CK4/13. The pannus tissue in clinically keratinized SJS expressed skin epidermal major cytokeratins, but the tissues of nonkeratinized SJS did not. Clinical observation and the use of our recently proposed grading system agreed with the immunohistological status with respect to keratinization, cell proliferation, and corneal/conjunctival cell typing. These findings facilitate our understanding of the pathogenesis of OCP and SJS, and will hopefully contribute to the development of future treatment strategies and improve predictions of the postoperative prognosis of ocular surface reconstruction in patients with OCP and SJS.

To determine the timing for follow-up study of power Doppler ultrasonography (PDUS) by evaluating the response of finger joint synovitis in patients with rheumatoid arthritis (RA) to treatment including infliximab, an antitumor necrosis factor alpha agent. Bilateral second/third metacarpo-phalangeal (MCP) joints and second proximal inter-phalangeal (PIP) joints (total of six joints) in 21 patients (18 women and three men; median age 53 years) with chronic active RA were assessed by PDUS before and after 2 weeks, 6 weeks, 14 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks of infliximab infusion. Pulse Doppler settings were standardized for each patient and optimized for the detection of synovial blood flow by adjustment of color gain, pulse repetition, and flow optimization. Power Doppler signal was graded for each joint [joint grade for power Doppler (JGPD) signals], and the sum of the grades of six joints was defined as the PDUS index [joint index for power Doppler signals (JIPD)] at each visit. PDUS and clinical parameters [28-joint disease activity score (DAS28), health assessment questionnaire, and C-reactive protein (CRP) level] were independently assessed and compared with baseline values. The American College of Rheumatology (ACR) core set responders and non-responders at week 54 were compared for clinical parameters and PDUS index at each visit. Fourteen patients completed the planned treatment for 1 year, while six patients dropped out for various reasons and one died suddenly. PDUS was performed a total of 146 times on 467 joints. DAS28 was assessed 127 times. Both DAS28 and JIPD had decreased at the follow-up. Comparative analysis between DAS28 and PDUS was available 125 times. The transverse correlation between the PDUS index and DAS28 was not significant throughout the follow-up period. When responders and non-responders were discriminated at week 54, a logistic regression model for the binary endpoint of responder vs non-responder, with PDUS index as explanatory variable at time point 0, and follow-up revealed statistical significance from week 38 and on. PDUS reflected infliximab’s effect on pannus vascular signals; this effect was observed as early as 2 weeks after treatment had begun. Also, the responders to treatment at 54 weeks tended to have fewer JIPD than non-responders in the follow-up period. PDUS may be performed at week 38 or later to foresee the response to the treatment at week 54.

As critical regulators of numerous cell signaling pathways, tyrosine kinases are implicated in the pathogenesis of several diseases, including rheumatoid arthritis (RA). In the absence of disease, synoviocytes produce factors that provide nutrition and lubrication for the surrounding cartilage tissue; few cellular infiltrates are seen in the synovium. In RA, however, macrophages, neutrophils, T cells and B cells infiltrate the synovium and produce cytokines, chemokines and degradative enzymes that promote inflammation and joint destruction. In addition, the synovial lining expands owing to the proliferation of synoviocytes and infiltration of inflammatory cells to form a pannus, which invades the surrounding bone and cartilage. Many of these cell responses are regulated by tyrosine kinases that operate in specific signaling pathways, and inhibition of a number of these kinases might be expected to provide benefit in RA.

Limbal stem cell deficiency (LSCD) is clinically characterized by growth of fibrovascular pannus onto the corneal surface, chronic inflammation and impaired visual acuity. The aim of this study was to characterize the pannus tissue. Total RNA was isolated from six pannus samples and protein from three pannus samples from patients with LSCD caused by chemical burns. Normal human corneal tissue (n=6) and conjunctiva (n=6) were used as control tissues. The expression of the epithelial lineage markers keratin 3 (K3), K19 and MUC5AC, the inflammatory markers IL-1beta, ICAM-1 and VEGF was analyzed by Western Blotting and/or real-time PCR. Normal corneal tissue had a higher expression of K3 and a lower expression of K19 and MUC5AC in comparison to normal conjunctiva. A higher expression of inflammatory markers was seen in conjunctiva compared to corneal tissue. The pannus tissue showed a similar expression of lineage markers to conjunctiva but a higher expression of most inflammatory markers as compared to both control tissues. The analyzed samples of pannus in LSCD resembled conjunctiva and not cornea and showed a high expression of inflammatory markers indicating chronic inflammation.

Panniculectomy surgery is performed to remove a massive pannus, or abdominal apron, which frequently contributes to a number of health concerns. The resection of such a massive abdominal panniculus is technically difficult due to the weight of the tissue and the difficulty in handling it during surgery.We performed a retrospective review on 20 morbidly obese patients (14 male, six female) who underwent a panniculectomy with a resection weight of6 kg between November 2003 and November 2007 at our department.The patients' weight ranged from 90 to 240 kg, with a mean weight of 157.6 kg. The redundant pannus weighed from 6.8 to 60.0 kg. Uncomplicated healing occurred in 55% of cases. Further complications were not observed.The treatment of a massive panniculus requires a multitask management considering optimal conditions for the surgeon and patient. Based on our experience from 20 patients over 4 years, we are able to present our standardized and improved technique using a mechanical lift and a tumescent solution to facilitate this procedure.

We describe a case of foramen magnum syndrome secondary to atlanto-occipital assimilation with spinal-cord compression caused by retro-odontoid fibrous pannus. Association of atlanto-occipital assimilation with the occurrence of severe neurological symptoms resulting from upper spinal cord compression remains rare in the literature. The embryonic process leading to this malformation is discussed. The anatomy and pathogenesis of this syndrome are described.

To report histopathologic changes of the ocular surface pannus in patients with severe limbal stem cell deficiency (LSCD). Corneal and conjunctival pannus tissues from 29 patients undergoing ocular reconstruction with cultured limbal cell transplantation were included. The medical records of these patients were reviewed for demographics, aetiologic diagnosis, type of injury, interval between the initial insult and excision of pannus, and medical history involving human amniotic membrane (HAM) or limbal transplantation. The paraffin-embedded tissues were reviewed for epithelial changes, type–degree of fibrosis, degenerative changes, vascular changes, conjunctivalization of corneal surface, and evidence of residual HAM. We attempted a clinicopathologic correlation to understand the pathogenesis of pannus formation in LSCD. The 29 tissues were from 29 eyes of patients with primary aetiology of chemical burn in 89.6% (undetermined in 10.4%) of cases. The pannus showed epithelial hyperplasia in 62%, active fibrosis in 66%, severe inflammation in 21%, giant cell reaction in 28%, and stromal calcification in 14% cases. Goblet cells were seen over the cornea in 64% cases; their absence was associated with squamous metaplasia of the conjunctiva and with long duration of insult. Evidence of residual HAM was noted in 42% cases. The commonest cause of severe LSCD is alkali-induced injury. Goblet cells over the cornea were seen in 60% of cases. HAM used for ocular surface reconstruction could persist for long periods within the corneal pannus, thus raising the need for further studies with long-term follow-up.

Introduction: Pannus formation and resulting cartilage destruction during rheumatoid arthritis (RA) depends on the migration of synoviocytes to cartilage tissue. Here, we focused on the role of hypoxia-inducible factor (HIF)-2 alpha-induced chemokines by chondrocytes in the regulation of fibroblast-like synoviocyte (FLS) migration into the cartilage-pannus interface and cartilage erosion. Methods: Collagen-induced arthritis (CIA), K/BxN serum transfer, and tumor necrosis factor-alpha transgenic mice were used as experimental RA models. Expression patterns of HIF-2 alpha and chemokines were determined via immunostaining, Western blotting and RT-PCR. FLS motility was evaluated using transwell migration and invasion assays. The specific role of HIF-2 alpha was determined via local deletion of HIF-2 alpha in joint tissues or using conditional knockout (KO) mice. Cartilage destruction, synovitis and pannus formation were assessed via histological analysis. Results: HIF-2 alpha and various chemokines were markedly upregulated in degenerating cartilage and pannus of RA joints. HIF-2 alpha induced chemokine expression by chondrocytes in both primary culture and cartilage tissue. HIF-2 alpha-induced chemokines by chondrocytes regulated the migration and invasion of FLS. Local deletion of HIF-2 alpha in joint tissues inhibited pannus formation adjacent to cartilage tissue and cartilage destruction caused by K/BxN serum transfer. Furthermore, conditional knockout of HIF-2 alpha in cartilage blocked pannus formation in adjacent cartilage but not bone tissue, along with inhibition of cartilage erosion caused by K/BxN serum transfer. Conclusion: Our findings suggest that chemokines induced by IL-1 beta or HIF-2 alpha in chondrocytes regulate pannus expansion by stimulating FLS migration and invasion, leading to cartilage erosion during RA pathogenesis.

Excessive pannus formation after implantation of a prosthetic valve is an infrequent but serious complication. A 69-year-old woman who had received a 19-mm CarboMedics aortic valve 11 years ago was readmitted to our hospital with dyspnea and chest oppression. Cineradiography did not show the restriction of valve movement. The aortic peak pressure gradient was calculated by Doppler echocardiography to be 104 mmHg. Based on the diagnosis of stenosis of the left ventricular outflow tract, the patient underwent reoperation. At reoperation, the pannus had formed circumferentially without disturbing the movement of the leaflet. A 19-mm St. Jude Medical Regent valve was implanted after enlargement of the aortic annulus. The patient's postoperative course was uneventful. We report this characteristic finding of pannus formation after the implantation of a CarboMedics valve in the aortic position.

High-frequency sonography enables excellent detection of early erosions and synovial proliferations. Power Doppler sonography (PDUS) allows for an improved characterization of articular and peritendinous augmented volume, because detection of hypervascularity correlates with inflammatory activity and further is helpful in differentiation from effusion and inactive pannus. The use of contrast media improves the sensitivity of vascularity detection, because they allow for a delineation of vessels at the microvascular level. This is of increased interest, as the development of new therapeutic options targeting the microvascular level calls for earlier diagnosis and optimal assessment of disease activity. Because of good availability, cost effectiveness, and patient acceptance, sonography facilitates early diagnosis of synovial proliferations and erosions as well as therapy follow-up.

Massive weight loss after bariatric surgery is associated with significant skin excess, laxity, and ptosis over the abdomen. Good results have been achieved with abdominoplasty and circumferential lipectomy. However, blood transfusions are sometimes needed, and patients may require long hospital stays. Furthermore, morbidity rates are high. Total abdominal liposuction performed with abdominoplasty allows for the preservation of lymphatic vessels below Scarpa’s fascia and eliminates the need for upper flap undermining. This study aimed to evaluate this technique in patients with anterior abdominal redundancy attributable to massive weight loss after bariatric surgery. The charts of 60 patients treated between December 2001 and October 2004 were retrospectively reviewed. All the patients had undergone previous bariatric surgery as well as subsequent total abdominal liposuction and abdominoplasty. The average amount of wetting solution used was 3.1 l, and the average total aspirate was 2.5 l. The mean pannus weight was 3,649 g, and the average dimension was 48 × 25 × 6 cm. No patient required a blood transfusion. The median in-hospital stay was 1 day, with 42% of the patients treated as outpatients. The median follow-up period was 3 months. Morbidity was 22%. Factors associated with the development of complications were weight of the pannus, transverse dimension of the pannus, and body mass index. All the patients were satisfied with the results. Total abdominal liposuction followed by abdominoplasty is adequate treatment for anterior abdominal redundancy for patients with massive weight loss.

A 64-year-old woman underwent aortic valve replacement with a 21-mm Advancing The Standard (ATS) open-pivot mechanical heart valve for bicuspid aortic valve stenosis. In addition to the appearance of a new cardiac murmur, echocardiography performed 3 years after surgery showed a high pressure gradient across the ATS valve and a reduction in the valve orifice area. Cineradiography of the valve revealed restricted leaflet opening. Subsequent multidetector-row computed tomography clearly demonstrated pannus overgrowth on the inflow aspect of the ATS valve. During a repeat operation, subvalvular overgrown pannus was confirmed and the ATS valve was replaced with a bioprosthetic valve. This is the first reported case of prosthetic valve dysfunction resulting from pannus formation in a patient with an ATS valve in the aortic position.

The aim of this study was to assess rheumatoid arthritis (RA) synovitis with positron emission tomography (PET) and( 18)F-fluorodeoxyglucose ((18)F-FDG) in comparison with dynamic magnetic resonance imaging (MRI) and ultrasonography (US).Sixteen knees in 16 patients with active RA were assessed with PET, MRI and US at baseline and 4 weeks after initiation of anti-TNF-alpha treatment. All studies were performed within 4 days. Visual and semi-quantitative (standardised uptake value, SUV) analyses of the synovial uptake of FDG were performed. The dynamic enhancement rate and the static enhancement were measured after i.v. gadolinium injection and the synovial thickness was measured in the medial, lateral patellar and suprapatellar recesses by US. Serum levels of C-reactive protein (CRP) and metalloproteinase-3 (MMP-3) were also measured.PET was positive in 69% of knees while MRI and US were positive in 69% and 75%. Positivity on one imaging technique was strongly associated with positivity on the other two. PET-positive knees exhibited significantly higher SUVs, higher MRI parameters and greater synovial thickness compared with PET-negative knees, whereas serum CRP and MMP-3 levels were not significantly different. SUVs were significantly correlated with all MRI parameters, with synovial thickness and with serum CRP and MMP-3 levels at baseline. Changes in SUVs after 4 weeks were also correlated with changes in MRI parameters and in serum CRP and MMP-3 levels, but not with changes in synovial thickness.(18)F-FDG PET is a unique imaging technique for assessing the metabolic activity of synovitis. The PET findings are correlated with MRI and US assessments of the pannus in RA, as well as with the classical serum parameter of inflammation, CRP, and the synovium-derived parameter, serum MMP-3. Further studies are warranted to establish the place of metabolic imaging of synovitis in RA.

A 32 year-old male patient was effectively immobilized secondary to morbid obesity. He underwent a gastric bypass which reduced his weight from 647 lbs to 376 lbs over 12 months. A massive abdominal panniculus persisted limiting his ability to pursue an effective exercise program and maintain appropriate hygiene. The patient was operated upon with the aid of Steinman pins to pierce the dependant portion of the pannus and an orthopaedic suspension device to facilitate its elevation. Operative excision of the 19.93 kg pannus proceeded in a rapid fashion with minimal difficulties in pannus manipulation. The technique of excision, its benefits and the case history are reviewed.

A 14-year-old boy presented with a 10-year history of the "sicca" form of seronegative juvenile idiopathic polyarthritis. Severely limited range of motion, pain, and capsular swelling in both small and large weight-bearing joints left him wheelchair-bound. Erythrocyte sedimentation rate and C-reactive protein were normal. Two-phase bone scan revealed tracer uptake of almost every joint at both early and late time points, indicating pathologic exudation and enhanced bone metabolism consistent with severe arthritis. However, radiographic studies revealed no erosive arthropathy but severe osteopenia, dysplastic bone changes, mega os trigonum, and platyspondylia. A magnetic resonance imaging (MRI) scan of the hips showed no signs of synovitis, pannus, or effusion but cartilage irregularities and subchondral cysts. These findings strongly suggested the diagnosis of progressive pseudorheumatoid dysplasia of childhood, an autosomal-recessive disorder of cartilage homeostasis. The patient carries a novel homozygous two-nucleotide deletion in exon 4 of the WISP3 gene. This genetic disorder is an important differential diagnosis of sicca polyarthritis.

We present three patients who underwent repeat aortic valve replacement for prosthetic valve dysfunction caused by tissue ingrowth in the late postoperative period. These patients (three women aged 48-51 years, mean 49.3 +/- 1.53 years) underwent operations for restriction of prosthetic valve leaflet movement by pannus in the left ventricular outflow tract. The interval from the previous operation ranged from 8.0 to 9.6 years (mean 9.6 +/- 2.0 years). The symptoms of the patients were New York Heart Association functional class I, II, and IV in one patient each. Diagnosis was made by cinefluoroscopy in two patients and aortography in one patient. The operative procedures consisted of aortic valve replacement ( n = 1) and aortic valve replacement with mitral valve replacement ( n = 2). Pannus was found at the left ventricular aspect of the prosthetic valve in all patients. In two patients, the pannus directly restricted movement of the leaflet and also severely narrowed the inflow orifice of the prosthetic valve. In the other patient, the pannus had grown at a distance of 7 mm from the valve and narrowed the left ventricular outflow tract circularly. The postoperative course was uneventful and all three patients were discharged in a good condition. One patient died of pneumonia 8 months after surgery and the other two patients have remained well and have been followed up for one and a half years. In conclusion, there may be a discrepancy between the clinical symptoms and the grade of subvalvular stenosis caused by pannus. Therefore, it is essential for satisfactory operative results that early diagnosis be made by various means.

The involvement of the cervical spine in patients with rheumatoid arthritis (RA) is common,and has recently received growing attention. In the early stage of the disease, there is an isolated atlantoaxial subluxation (AAS). With further progression, osseous destruction of the joints can lead to vertical instability. While the involvement of the middle and lower cervical spine can cause a subaxial instability, neurological deficits can occur at any time. The onset of cervical myelopathy in patients with RA is often missed because of additional problems related to the hands and feet. If patients show clear symptoms of cervical myelopathy, the progression of the disease cannot be stopped by conservative treatment. Other indications for operative treatment are severe pain and radiological evidence of progressive instability. In the case of an isolated AAS, fusion can be restricted to the C1/C2 segment. If there is evidence for vertical or subaxial instability, an occipitocervical fusion has to be performed. To avoid instability adjacent to the fusion, the surgeon must check for signs of potential subaxial instability. If this is the case, fusion should include the entire cervical spine. Additional transoral decompression may be necessary when there is persistent retrodental pannus or osseous compression by an irreducible transverse dislocation or cranial migration of the dens. Non-ambulatory myelopathic patients are more likely to present severe surgical complications with limited prospects of functional recovery. Therefore, it is important to avoid the development of severe cervical myelopathy by early surgical intervention.

Die Keratitis superficialis chronica des Hundes ist eine unbehandelt fast immer progredient verlaufende Hornhautentzundung, die zur Erblindung fuhren kann. Eine Standardbehandlung gibt es bisher nicht. Systematische Untersuchungen zur Bestrahlung mit Strontium-(Sr-)90 liegen praktisch nicht vor, die Anwendung wird jedoch immer wieder propagiert. Ziel der Untersuchung war es, Wirksamkeit und Nebenwirkungen dieser Therapie zu dokumentieren.

Rheumatoid arthritis (RA) is a systemic disorder characterized by synovial inflammation and subsequent destruction and deformity of synovial joints. The articular lesions start with synovitis, focal erosion of unmineralized cartilage, and then culminate in the destruction of subarticular bone by pannus tissue. Periarticular osteopenia and systemic osteoporosis follow as late complications of RA. Osteoclasts, specialized cells that resorb bone, play a central role in developing these osteolytic lesions. To elucidate the mechanism of osteoclastogenesis and bone destruction in autoimmune arthritis, we investigated the expression of RANK ligand (RANKL), RANK, and osteoprotegerin (OPG) mRNA in a mouse type II collagen-induced arthritis (CIA) model by in situ hybridization. The results indicated that most of the TRAP-positive mono- and multinucleated cells in the inflamed and proliferating synovium and in the pannus were RANK-positive authentic osteoclasts and their precursors. In the inflamed synovium and pannus of the mouse CIA model, synovial fibroblastic cells around these RANK-positive cells were strongly positive for RANKL. Moreover, RANKL-positive osteoblasts on the endosteal bone surface, at a distance from the affected synovial joints, increased significantly in the mouse CIA model prior to periarticular osteopenia and systemic osteoporosis. These data indicated that the RANKL-RANK system plays an important role for osteoclastogenesis in both local and systemic osteolytic lesions in autoimmune arthritis, and can therefore be a good target for therapeutic intervention.

Neovascularization of the inflamed synovium and pannus is one of the hallmarks of chronic rheumatoid arthritis. It contributes to disease progression by supplying blood to the inflamed tissues and by recruiting immune competent and inflammatory cells. Angiogenesis is tightly regulated at several levels, but of significant importance is transcription. The Ets 1 transcription factor has been intimately linked to the regulation of angiogenesis under both physiological and pathological conditions and is induced in endothelial cells by vascular endothelial growth factor, the most important angiogenic factor in rheumatoid arthritis. We investigated Ets 1 expression in synovial membranes of joints in patients with active rheumatoid arthritis and compared the results to those obtained in patients with degenerative joint disease, which is characterized by significantly less neoangiogenesis. Using quantitative densitometric and real-time RT-PCR approaches, we found a significant upregulation of Ets 1 transcripts in rheumatic, compared to osteoarthritic, synovial membranes. Moreover, we were able to attribute both Ets 1 mRNA and Ets 1 protein to capillary endothelial cells of newly formed blood vessels by in situ hybridization and immunohistochemistry. Finally, our data suggest important roles of the Ets 1 transcription factor in the regulation of inflammatory angiogenesis in rheumatoid arthritis.

Cloth-covered Starr-Edwards caged ball valves implanted in the aortic and mitral valve positions for 39 years were extracted. Both showed valve dysfunction resulting from pannus overgrowth. The metal cages of the Starr-Edwards valves were covered with worn cloth. This case indicates the extended durability of Starr-Edwards valves and the importance of the design and materials of prosthetic heart valves to avoid pannus overgrowth and prosthetic valve abrasion.

Diagnosis of corneal intraepithelial neoplasia was missed in a patient who presented with recurrent large epithelial defects with pannus. The patient was eventually diagnosed and successfully treated with topical mitomycin C. Mitomycin C may be preferable to surgery in lesions with extensive corneal involvement. Impression cytology should be used for early diagnosis in suspicious lesions.

The most common diseases of the joints and its tissues are osteoarthritis and rheumatoid arthritis, with osteoarthritis being anticipated to be the fourth leading cause of disability by the year 2020. To date, no truly causal therapies are available, and this has promoted tissue engineering attempts mainly involving mesenchymal stem cells. The goal of all tissue repairs would be to restore a fully functional tissue, here a hyaline articular cartilage. The hyaline cartilage is the most affected in osteoarthritis, where altered cell-matrix interactions gradually destroy tissue integrity. In rheumatoid arthritis, the inflammatory aspect is more important, and the cartilage tissue is destroyed by the invasion of tumor-like pannus tissue arising from the inflamed synovia. Furthermore, the fibrocartilage of the meniscus is clearly involved in the initiation of osteoarthritis, especially after trauma. Recent investigations have highlighted the role of migratory progenitor cells found in diseased tissues in situ. In osteoarthritis and rheumatoid arthritis, these chondrogenic progenitor cells are involved in regeneration efforts that are largely unsuccessful in diseased cartilage tissue. However, these progenitor cells are interesting targets for a cell-based regenerative therapy for joint diseases.

Background: Many patients who qualify for obesity surgery have a moderate to large panniculus (grade 1-5). They can benefit from panniculectomy done concurrently with gastric bypass (GBP) or subsequently after significant weight reduction, usually 18 months after the GBP. Method: Over the last 8 years, 2,231 bariatric operations were performed at the Center. 577 panniculectomies were done, with 428 (74.2%) concurrent with the GBP and 149 (25.8%) subsequent to the GBP. Results:The redundant pannus weighed from 5 to 54.5 kg. Wound problems occured in 15.1% of panniculectomies. Transfusion was necessary in 1.9%. Hospital stay was 4 to 5 days, and was no greater than in patients that underwent the GBP alone. Those with grades 3-5 suffer more back-pain and problems of hygiene resulting from panniculitis. Conclusion: A very redundant panniculus compounds the patient's physical, social and emotional problems. Where cardiopulmonary and other medical status are satisfactory,a panniculectomy may be offered to patients with a symptomatic panniculus at the time of bariatric surgery, as a physically beneficial and cost-effective adjuvant.

The aim of this study was to depict and characterize inflammatory soft tissue proliferations caused by rheumatoid arthritis (RA) in the craniocervical region by unenhanced and contrast-enhanced CT. Computed tomography of the craniocervical region was performed in 35 patients in the axial plane before and after the i. v. administration of contrast material. According to the densities and contrast enhancement of the inflammatory soft tissue proliferations, four groups were classified. Ancillary findings, such as a compression of the dural sac or spinal cord, erosions of the bony structures, and atlantoaxial subluxation, were also evaluated. Inflammatory soft tissue proliferations were depicted in 28 of 35 patients and could be differentiated by unenhanced and contrast-enhanced CT according to the above defined criteria: effusion in 6 patients (17 %); hypervascular pannus in 8 (23 %); hypovascular pannus in 5 (14 %); and fibrous tissue in 9 patients (26 %). A compression of the dural sac was seen in 11 (31 %) patients; 3 of these had neurological symptoms. Erosions of the odontoid process were found in 20 (57 %) patients; 16 (80 %) of these also showed erosions of the atlas. Atlantoaxial subluxation was seen in 11 (31 %) patients. Inflammatory soft tissue proliferations in the craniocervical region caused by RA can be reliably demonstrated and classified by unenhanced and contrast-enhanced CT, which can differentiate between joint effusion and various forms of pannus and depict ancillary findings. Computed tomography is an alternative method for patients unable to undergo an MRI examination.

No long-term survivals over 20 years after valve replacement with SAM (Sakakibara-Arai-Mera) valve prostheses have been described. We report a 57-year-old woman who survived for 31 years after mitral valve replacement with the SAM valve (Type M, 5M). Echocardiography revealed remarkable dilatation of the left atrium and moderate tricuspid regurgitation. Cineradiography, however, showed no restricted or asymmetric disc movement of the SAM valve. Cardiac catheterization revealed moderate pulmonary hypertension (64/30mmHg), with a mean pulmonary capillary wedge pressure of 25mmHg and a mean transprosthetic pressure gradient of 13mmHg. The mitral valve area was calculated to be 0.9 cm2. No findings of pannus overgrowth around the SAM valve were confirmed on echocardiograms or left ventriculograms. Although the diagnosis of prosthetic valve obstruction resulting from pannus formation was suspected, the patient strongly refused replacement of the SAM valve because of her poor prognosis with bilateral breast cancer with systemic metastases. We believe that this patient may be the last living patient with the SAM valve.