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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 ​

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.

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.

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.

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.

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.

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.

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.

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

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.

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 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

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.

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.

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.

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.

Background and importance: Synovial cysts of the cranio-cervical junction constitute an uncommon pathology in neurosurgical practice. Different surgical approaches have been described for treating those lesions including trans-oral microsurgical approaches, endoscopic endo-nasal approaches and sub-occipital trans-dural approaches. Objective: The purpose of this article is to describe a case of resection of a retro-odontoid synovial cyst through a modified far-lateral trans-atlas extradural approach. A detailed surgical plan with cadaveric dissection is presented as well as literature review of surgical approaches. Methods: The authors describe an 86-year-old man presenting with gradual deterioration of his gait as well as upper and lower extremities weakness. He was found to have an odontoid pannus accompanied by midline retro-odontoid cyst on MRI. An anatomical cadaveric dissection describing the modified far-lateral trans-atlas extradural approach is described and then used to completely resect the cystic lesion, decompress the brain stem and perform a fusion of the cranio-cervical junction. Result: This surgical technique allows for the decompression and fusion to be performed in the same operative time, avoids the contaminated surgical fields encountered during anterior approaches and prevents CSF leakage by avoiding dura opening. Conclusion: Modified Far-Lateral Transatlas Approach offers several advantages when compared with the other options and can provide an alternative to treat these patients. Keywords: Far-lateral approach, Odontoid pannus, Operative technique, Retro-odontoid cyst, Synovial cyst

Aim: to assess the contribution of primary tissue failure, calcification, bacterial contamination and pannus to bioprosthetic valve dysfunction. Materials and methods . To evaluate degenerative changes of the «UniLine» bioprosthesis explanted from the mitral position with macroscopic examination, light and scanning electron microscopy, and micro-computed tomography (micro-CT). Light microscopy was used to analyze cell composition, the presence of bacteria, the localization of calcific deposits and recipient cells. Scanning electron microscopy allowed confirming the presence of bacteria. Micro-CT was used to evaluate the deformation of the bioprosthetic elements, the distribution of calcific deposits and their volume in the valve tissue. Results. The presence of pannus, calcification, primary tissue failure and bacterial contamination were found among the causes leading to bioprosthetic dysfunction. Prosthetic leaflets showed pannus growth from the inflow tract. Excessive circumferential pannus extended into outflow tract. Calcific deposits were mostly localized in the commissural zone and the central portion of the leaflets. The total volume of calcification accounted for 1/3 of the bioprosthetic tissue component. The relationship between calcification and stress-strain properties of the bioprosthetic elements has been indicated. The asymmetric deformation of the bioprosthetic stent frame and leaflets with 1.5-fold thickening of the last has been found. The areas with loose and fragmented collagen and elastic fibers contained red blood cells and neutrophils. Endothelial cells and fibroblastic cells were present in the outer surface layers. There were no signs of calcification in the areas accumulating cells and bacteria. Conclusion. We can assume that primary tissue failure, calcification, bacterial contamination and pannus independently contribute to the onset of bioprosthetic heart valve dysfunction.

Background Dynamic contrast-enhanced magnetic resonance imaging has the potential to show disease activity of rheumatoid arthritis even in complex anatomic areas as the atlantodental region. Purpose To demonstrate the technical feasibility of measuring synovial volume and perfusion characteristics with dynamic contrast-enhanced magnetic resonance imaging of the atlantodental region in patients with rheumatoid arthritis. Material and Methods Ten patients with rheumatoid arthritis and cervical spine involvement underwent dynamic contrast-enhanced magnetic resonance imaging of the cervical spine at 1.5 T. For each patient, 80 3D datasets were acquired using the commercialized Time Resolved Imaging of Contrast KineticS (TRICKS) sequence. Volumes of synovia with active synovitis on anatomical and parametric images were segmented. Synovial tissue perfusion parameters, namely plasma flow (Fp), relative plasma volume (vp), and the permeability-surface area product (PS), were calculated using a two-compartment uptake model. Statistical analysis included calculation of intra- and inter-reader agreement and a correlation of perfusion parameters with Outcome Measures in Rheumatology Clinical Trials (OMERACT) criteria. Results Dynamic contrast-enhanced magnetic resonance imaging as well as quantification of volume and perfusion characteristics of synovia was successful in most patients (80%). Intra- and inter-reader agreement was excellent (0.89–0.99). There was a positive correlation between OMERACT score and the permeability-surface product. Conclusion Dynamic contrast-enhanced magnetic resonance imaging using a 4D angiography sequence for the atlantodental region in patients with rheumatoid arthritis for quantitative and qualitative assessment of synovial volume and perfusion characteristics is technically feasible.

Background: Prosthetic Mitral valve dysfunction is a serious complication associated with a high mortality rate particularly in obstructive cases. The number of cases undergoing redo mitral valve surgery is increasing. This study aims to identify the risk factors of mortality and morbidity in patients who underwent redo mitral valve surgery for prosthetic mitral valve dysfunction. Methods: This study was conducted on 80 patients who underwent re-operation for management of prosthetic mitral valve dysfunction from December 2014 to February 2018. Patients’ age ranged between 21 and 58 years with a mean of 36.8±9.60 years, and 53 patients (66.3%) were males. The causes of mitral valve malfunction were thrombus in 67 patients (83.7%) and pannus in 13 patients (16.3%). Results: 53 patients (66.25%) had urgent surgical intervention. Thrombectomy or pannus resection was done in 75 patients (93.75%) and valve replacement in 5 patients (6.25%). Re-exploration was required in 11 patients (13.75%) and was significantly associated with diabetes (p= 0.004), preoperative liver dysfunction (p= 0.04), elevated INR (p= 0.006), trial of thrombolysis (p

Objective.Pannus formation in the atlanto-axial joint is a well-recognized complication of rheumatoid arthritis (RA). Occasionally, atlanto-axial pannus is reported when patients without a history of RA undergo magnetic resonance imaging (MRI) of the cervical spine. We sought to further characterize these patients.Methods.The Partners HealthCare Research Patient Data Registry was free-text searched for “atlanto-axial” AND “pannus” in cervical spine MRI reports from 2001 to 2015. Cases with MRI reports describing pannus were reviewed. Clinical data were extracted by chart review in cases with confirmed atlanto-axial pannus (n = 105).Results.Twenty-nine patients (27.6%) had RA, all of whom except one carried this diagnosis at the time of the MRI scan. Only 1 of 77 patients without a history of RA was subsequently diagnosed with RA (1.3%, 95% CI 0.1–7.0%, median followup 3.6 yrs). Non-RA patients were significantly older (median age 79 vs 63 yrs, p < 0.0001), less frequently female (55% vs 86%, p = 0.0032), and more likely to have undergone prior cervical spine surgery (18% vs 0%, p = 0.016) compared with RA patients. Thirty-four non-RA patients (44.7%) either had a clinical diagnosis of calcium pyrophosphate dihydrate disease (CPPD) or imaging evidence for tissue calcification. There were no significant differences in age or sex between the CPPD subgroup and other non-RA patients. Twenty-eight patients (26.7%) underwent cervical spine surgery.Conclusion.Patients without RA diagnosis and incidental atlanto-axial pannus on cervical spine MRI are unlikely to have previously unrecognized RA. Degenerative disease and tissue calcification may contribute to pannus formation in these patients.

Pannus refers to synovial tissue proliferation, and has been considered a late, inactive and irreversible manifestation of rheumatoid arthritis (RA), contrary to historical findings. A literature search was performed on terminology about pannus and its historical role in the pathophysiology of RA. Light microscopy studies have shown the destructive impact of pannus tissue with very specific abnormalities, corroborated a year later with electronic microscopy. Some of these findings are the isolation of the immunological cells inside the tissue, especially one cell line with particular capacities, called synoviocytes similar to fibroblasts. This cellular component is the source a large quantity of cytokines and proteinases that perpetuate and cause bone and cartilage damage. Inflammation has been seen in many image techniques, such as magnetic resonance and ultrasound. These show the role of tissue widening and hyper-vascularization in tissue damage, and some reversibility after treatment of RA. With the evidence presented it is possible to conclude that pannus refers to a histological (more than clinical) term for synovial hypertrophy, and includes a large component of cell activity that generates and perpetuates inflammation and thus the disease.

This work investigates whether the use of an avoidance sector in a two-arc volumetric modulated arc therapy (VMAT) prostate stereotactic body radiotherapy (SBRT) plan reduces dosimetric variations due to an irreproducible pannus. A morbidly obese patient with favorable-risk prostate cancer elected treatment with SBRT. The patient was treated with the avoidance arcs across the pannus to eliminate reproducibility issues created by daily pannus variability in set up. For post-treatment assessment, the case was planned using Varian Eclipse™ treatment planning system (TPS) with two VMAT arcs with and without 100° avoidance sectors across the pannus. The dose was re-calculated using the external body contour from four daily treatment cone-beam computer tomography scans, and on two virtual body contours created by expanding the pannus region of the external contour by 5 and 10 mm. Dose differences between planned and re-calculated rectal wall mean dose and the V24Gy were numerically larger in the absence of the avoidance sector for all fractions and for both simulated pannus variations, with maximum changes of 2.6% and 1.3%. Maximum point dose variations in the PTV, CTV, rectum, bladder, and femoral heads were 105 cGy or less for all cases, with and without the avoidance sector. The use of an avoidance sector across this large, asymmetrical pannus did not inhibit achieving dose constraints and provided a reduction in dose variability which was nominal in this case for 10 mm variations. Avoidance sectors can be safely implemented in cases with obvious reproducibility concerns in the setting of prostate VMAT SBRT.

Background: We report a case of an elderly patient who was diagnosed with lateral atlantoaxial subluxation with type II odontoid fracture, an extremely uncommon upper cervical spine injury that has not been previously reported in the literature to the knowledge of the authors. Methods: An 87-year-old male reported to the emergency room following a syncopal episode after sustaining a fall. He complained of dizziness, fatigue, disruption of vision and audition, and worsening neck pain. Computed tomographic scans were positive of partial dislocation of the C1 relative to C2 and chronic fracture of dens classified as type II according to the Anderson and D9Alonzo classification system. Magnetic resonance imaging further revealed large fracture pannus tissue at the level of the dens, reducing the space in the spinal cord. There was no evidence of spinal cord injury. Atlas-axis fusion with instrumentation was performed to manage the injury. A review of the classification, occurrence, and management of upper cervical spine surgeries was performed. Results: An acute injury to a previously unrecognized type II odontoid fracture with partial C1-C2 dislocation was identified as a rare upper cervical spine injury and classified based on the Anderson and D9Alonzo and Fielding and Hawkins classification systems. The decision was made to perform instrumented spinal fusion by inserting mass screws into C1, pars screws into C2, and locking rods to realign the vertebral bodies and address the atlantoaxial instability. Follow-up scans indicated good postsurgical reduction and fixation, including resolution of the pannus overgrowth without direct intervention. Conclusions: Lateral atlantoaxial subluxation with chronic type II fracture of the dens constitutes a rare injury of the upper cervical vertebrae. Posterior instrumented spinal fusion was used to effectively manage the injury, leading to reabsorption of retro-odontoid pannus tissue.

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

Objective Vascular groin incision complications contribute significantly to patients' morbidity and rising health care costs. Negative pressure therapy over the closed incision decreases the infection rate in cardiac and orthopedic procedures. This study prospectively evaluated negative pressure therapy as a means to decrease wound complications and associated health care costs. Methods This was a randomized, prospective, single-institution study of 119 femoral incisions closed primarily after elective vascular surgery including both inflow (eg, aortofemoral) and outflow (eg, femoral-popliteal bypass) procedures. Incisions were categorized as high risk for wound complications on the basis of body mass index >30 kg/m2, pannus, reoperation, prosthetic graft, poor nutrition, immunosuppression, or hemoglobin A1c >8% and randomized 1:1 to standard gauze (n = 60) dressing vs negative pressure therapy (Prevena [Acelity, San Antonio, Tex], n = 59). Wound complication rate, length of stay (LOS), reoperation, readmission, and variable hospital costs were determined during 30 days. Statistical analysis was performed using χ2 test along with a two-sample unpaired t-test for continuous variables. Results There were no significant demographic differences (age, sex, risk factors for wound complication) between the two high-risk groups. In low-risk controls, the major wound complication rate was 4.8% (involving one infection in 21 incisions), resulting in a 3.8-day LOS, 4.8% reoperation, 4.8% readmission rate, and $17,599 in average variable cost. For high-risk controls, there was a significant increase in major wound complications to 25% (including all 12 infections in 60 incisions), LOS (10.6 days), reoperation (18.3%), readmission (16.7%), and costs ($36,537). Finally, negative pressure therapy significantly reduced major wound complications to 8.5% (including five of six infections in 59 incisions; P Conclusions This study suggests that negative pressure therapy significantly reduces the major wound complication, reoperation, and readmission rates for patients at high risk for groin wound complications. Furthermore, this therapy may lead to a reduction in hospital costs. Negative pressure therapy for all groin incisions considered at high risk for wound complications is recommended.

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.

OBJECTIVES To evaluate the accuracy of predicted prosthesis-patient mismatch (PPM) regarding actual PPM measured postoperatively. To assess the association between PPM and prosthetic valve dysfunction. METHODS Retrospective cohort study including adult patients after aortic valve replacement surgery with a biological prosthesis. Predicted PPM status was determined using mean reference effective orifice area indexed to total body surface (iEOA), without considering reference standard deviations. Postoperative PPM status was determined by measuring iEOA within the first 60 postoperative days. Prosthetic valve dysfunction was defined as thrombosis, pannus, valve degeneration, and/or disruption. RESULTS 205 patients were enrolled between January 2003 and June 2017: predicted PPM was absent in 52 patients (25.4%), moderate in 137 patients (66.8%), and severe in 16 patients (7.8%). After surgery, the actual postoperative iEOA was measured: 53 (25.9%) did not have PPM, 73 had moderate PPM (35.6%), and 79 had severe PPM (38.5%). Predicted PPM identified the presence of hemodynamically significant actual postoperative PPM (OR = 2.56; 95%CI 1.30-5.05; P = .006), though not its degree of severity. Prosthetic valve dysfunction was more frequent among patients with hemodynamically significant PPM (53.9% vs. 11.3%; P

PurposeMolecular pathogenesis underlying persistent ocular surface inflammation in chronic Stevens-Johnson syndrome (SJS) still remains largely unexplored. The present study investigates the expression of matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP11 and TIMP1 (tissue inhibittor of matrix metalloproteinase 1) in pannus tissues of chronic ocular SJS undergoing cultivated oral mucosal epithelial transplantation (COMET) and their prognostic relevance.MethodsIn this prospective study, 45 eyes with chronic SJS underwent COMET for visual and anatomical rehabilitation. Preoperative and postoperative clinical parameters were documented. MMP2, MMP3, MMP9, MMP11 and TIMP1 expression were assessed using immunohistochemistry and quantitative real time PCR. Inflammadry MMP9 assay was performed at 1-year follow-up. Kaplan-Meier curves and Cox proportional hazard models were used to correlate protein expression with clinicopathological parameters and COMET graft survival outcomes.ResultsMMP9 and MMP11 positivity was seen in both pannus epithelia (48% and 55%, respectively) and in stromal layer (57% and 33%, respectively) while MMP2 and MMP3 showed only pannus epithelial positivity in 35% and 51% cases, respectively. High MMP9 stromal expression was significantly associated with preoperative corneal keratinisation (p=0.011), conjunctival hyperaemia (p=0.014), symblepharon (p=0.028). High MMP9 and MMP3 epithelial expression were found to be independent risk factors for poor best-corrected visual acuity (BCVA) outcomes post-COMET (p=0.022 and p=0.048). Multivariate analysis revealed MMP9 to be the best prognostic marker (p=0.050).ConclusionOur findings suggest that differential expression of MMPs and TIMP1 is seen in SJS in chronic stage. Emergence of MMP9 as a poor prognostic predictor of BCVA post COMET and postoperative MMP9 immunoassay positivity could be a useful tool in further studies to understand the unresolved ocular surface inflammation seen in SJS.

A 34-year-old woman was hospitalized with shortness of breath and chest tightness and pain. She had undergone aortic valve replacement for aortic stenosis at the age of 18 years. Transthoracic echocardiography showed left ventricular asynergy and a high aortic valve pressure gradient. Thus, structural valve deterioration was diagnosed. Coronary computed tomography and coronary angiography revealed left main trunk ostial stenosis that had caused acute anteroseptal myocardial infarction. Urgent surgery revealed pannus formation around the prosthetic valve and covering the ostium of the left main trunk. A Bentall procedure and coronary artery bypass grafting were performed. The postoperative course was uneventful.

ObjectiveThe aim of this study was to assess the safety of poly-lactic co-glycolic acid (PLGA) electrospun membranes as carriers for limbal tissue explants for treatment of limbal stem cell deficiency (LSCD).Methods and analysisApproval was obtained for a first in-man study from the Drug Controller General of India. PLGA membranes were applied to the affected eye of five patients after removal of the vascular pannus. Simple limbal epithelial transplantation was performed and limbal explants were secured on the membrane using fibrin glue followed by a bandage contact lens. Patients were followed up for 1 year with ocular exams including slit lamp exam, corneal thickness measurements, intraocular pressure measurements and recording of corneal vascularisation and visual acuity. Systemic examinations included pain grading, clinical laboratory assessment, blood chemistry and urine analysis at baseline, 3 and 6 months after surgery.ResultsPLGA membranes completely degraded by 8 weeks post-transplantation without any infection or inflammation. In all five patients, the epithelium regenerated by 3 months. In two in five patients, there was a sustained two-line improvement in vision. In one in five patients, the vision improvement was limited due to an underlying stromal scarring. There was recurrence of pannus and LSCD in two in five patients 6 months after surgery which was not attributable to the membrane. The ocular surface remained clear with no epithelial defects in three in five subjects at 12 months.ConclusionPLGA electrospun membranes show promise as carrier for limbal epithelial cells in the treatment of LSCD.

Objective The potential significance of relationship of atlantoaxial instability with retro-odontoid pseudotumor, pannus, and/or cyst (RPC) is analyzed. Methods We searched the database of patients with craniovertebral junction–related instability treated by atlantoaxial fixation from January 2000 to March 2020. We identified 63 patients in whom there was an RPC in the region posterior to the odontoid process or posterior to the posterior aspect of the C2 body. Results The RPC was solid in 10 patients, predominantly cystic in 39 patients, and had both solid and cystic components in 14 patients. The vertical dimension of the RPC varied from 4.5 to 10.5 mm (average, 7.9 mm) and the transverse dimension ranged from 2 to 5.2 mm (average, 3.4 mm). In 51 patients, the RPC was in the midline and in 9 patients, it was eccentric in location. In 38 patients, there was erosion of the C2 body adjoining the RPC. Analysis of investigations showed that in 100% of patients, the dome of the RPC was in line with the most susceptible point of potential bone compression of neural structures. The RPC was eccentric in location in 9 patients presenting with torticollis. RPC indicated the presence of atlantoaxial instability even when there were no other positive and validated radiologic indicators. After atlantoaxial stabilization, the RPC spontaneously regressed or disappeared. Direct resection of the RPC was neither performed nor was necessary in any case. Conclusions RPCs are secondary consequences of atlantoaxial instability and need not be primarily addressed by surgical resection. Their location suggests that they might have a neural protective function.

Non-neoplastic craniovertebral junction lesions are well known with various etiologies.1,2 They are frequently associated with craniovertebral junction instability. Many require only stabilization for their management.2 However, when significant irreducible anterior compression is present, surgical decompression becomes necessary.2-4 The traditional decompression route is direct anterior, such as the transoral, transmaxillary, or endoscopic endonasal approaches with a separate posterior stabilization.1,2 The transcondylar approach offers a wide and direct exposure to the anterolateral foramen magnum and atlantoaxial space, allowing extensive decompression, total resection of the odontoid, and associated pannus, even with large lateral extension, as well as fusion in the same surgical setting.5 The surgical manipulation is parallel to the dural sac in the sagittal plane, which could be safer than perpendicular dissection.5 Understanding the regional anatomy allows safe exposure and transposition of the vertebral artery with the surrounding alveolar and venous plexus (suboccipital cavernous sinus).5-7 We present this technique's details in a case of a 72-yr-old female who presented with progressively worsening bilateral upper extremity weakness and significant anterior compression due to irreducible odontoid degenerative changes. We demonstrate the steps necessary to achieve adequate exposure and decompression. The patient agreed to the surgical intervention. Images at 2:46, 3:00, and 3:25 reused from Al-Mefty et al,5 by permission from JNSPG. Images at 9:28 from Symonds et al,3 by permission of Oxford University Press. Image at 2:15, © Ossama Al-Mefty, used with permission.

OBJECTIVES To describe diagnosis, CT findings, management and short-term outcome of a large population of canine pyothorax cases. METHODS Retrospective analysis of 101 canine pyothorax cases at two UK referral centres. Medical records and CT images were reviewed. Dogs were included if pre- and post-contrast CT was performed within 48 hours of presentation. RESULTS CT abnormalities included pleural thickening (84.1%), pannus (67.3%), pneumothorax (61.4%), mediastinal effusion (28.7%), pulmonary (13.8%) and mediastinal (7.9%) abscessation, foreign body presence (7.9%), foreign body tracts (6.9%) and pneumonia (6.9%). Seventy-one percent of dogs were managed surgically, of which 90.2% survived, and 29% were managed medically, of which 72.4% survived. Overall mortality was 14.8% and 86.6% of these dogs died within 48 hours of admission. All dogs with evidence of a foreign body on CT underwent surgery. CLINICAL SIGNIFICANCE Mortality in our population was low and most dogs that died did so within 48 hours of hospitalisation, regardless of management type.