Search

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

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

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

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

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.

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

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

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.

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.

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

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.

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

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

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

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

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.

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.

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

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.

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.

Purpose We want to share our experience of Sorin Bicarbon prosthesis (SBP) after 19 years follow-up. Methods Retrospective study of 1377 patients who had replaced with SBP from May 1998 to December 2008 at Ho Chi Minh Heart Institute, Viet Nam. Results Male patients was 42%, mean age was 40.2 ± 11.8 years. Atrial fibrillation was 43.5%. The main cause of valvular disease was rheumatic fever (89.8%). Isolated mitral valve replacement (MVR): 54% (744), isolated aortic valve replacement (AVR): 18% (247), double valve replacement (DVR): 26% (359), and 27 AVR plus mitral repair. 30-day mortality for all was 1.5%. Mean time of follow-up was 153 ± 53.1 months with total follow-up time was 17563 patients-years. 2.5% lost of follow-up. Late death was 77 cases. Redo for all causes was 59 cases. 19 years survival was 88.8 ± 1.8%. 19 years freedom of redo was 76.4 ± 4.7%. Linearized rate of all valve thrombosis, embolism, severe bleeding, endocarditis, and pannus were 0.31%, 0.28%, 0.267%, 0.068%, and 0.165% patient-years, respectively. Conclusions SBP had shown very good results in long term and still have a reliable mechanical valve.

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.

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.

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.

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.

As a calcium antagonist, the mechanism of nifedipine for treating chilblain has not been reported. In the present study, we established the chilblain model by using -20 ℃ 95% ethanol to freeze the right back foot of SD rats, and investigated the effects of this drug. Hematoxylin-eosin (HE) examination indicated most of pannus in the skin tissue of chilblain rats had disappeared, and the local inflammatory cells were also greatly reduced when given nifedipine at 15.0 mg/kg/d. The enzyme-linked immunosorbent assay (ELISA) revealed that nifedipine inhibited release of inflammatory factors TNF-α, IL-6, IL-1β and VEGF in serum. The RT-PCR analysis showed that nifedipine down regulated mRNA levels of TRPC-6 and VEGF in skin tissue. Furthermore, immunohistochemical examination showed nifedipine inhibited expression of IL-1β, IL-6, and TNF-α inflammatory protein and further inhibited expression of TRP (transient receptor potential) family proteins TRPM-7, TRPC-1, TRPC-3 and TRPC-6 and reduced expression of VEGF in skin and relieved erythema and oedema. This study demonstrated that nifedipine as an old medicine can be new use for the treatment of chilblain by acting on TRPs family and inflammatory proteins.

Angiogenesis is an early and key event in the pathogenesis of rheumatoid arthritis (RA) and is crucial for the proliferation of synovial tissue and the formation of pannus. This process is regulated by both angiogenesis-stimulating factors and angiogenesis inhibitors, the basis for the "on-off hypothesis of angiogenesis." In RA, inflammation, immune imbalance, and hypoxia can further turn on the switch for blood vessel formation and induce angiogenesis. The new vasculature can recruit white blood cells, induce immune imbalance, and aggravate inflammation. At the same time, it also can provide oxygen and nutrients for the proliferating synovial tissue, which can accelerate the process of RA. The current therapies for RA mainly target the inflammatory response of autoimmune activation. Although these therapies have been greatly improved, there are still many patients whose RA is difficult to treat or who do not fully respond to treatment. Therefore, new innovative therapies are still urgently needed. This review covers the mechanism of synovial angiogenesis in RA, including the detailed process of angiogenesis and the relationship between inflammation, immune imbalance, hypoxia, and synovial angiogenesis, respectively. At the same time, in the context of the development of angiogenesis inhibition therapy for cancer, we also discuss similar treatment strategies for RA, especially the combination of targeted angiogenesis inhibition therapy and immunotherapy.

It was previously observed that two dimensional (2D) Doppler derived and real-time three-dimensional (RT-3D) directly measured valve areas were smaller than reported manufacturer sizes. It may be helpful to obtain the ranges of inner diameters (IDs) and the geometric orifice area (GOA) during evaluation of prosthetic mitral valves. In this study, we aimed to provide reference dimensional parameters of bileflet mitral mechanical prosthetic valves. Patients with recent mitral valve replacement were examined by 2D and RT-3D transesophageal echocardiography (TEE) in the early postoperative period when the presence of pannus overgrowth was unlikely. Measurements of 2D IDs, 3D hinge to hinge (HHD) and edge to edge diameters (EED) and 3D GOA were obtained and compared with reported manufacturer sizes and areas. This study enrolled 126 patients with mitral prosthetic valves (38 ATS, 42 Carbomedics, 46 St. Jude Medical, all bileaflet). The measured 2D and 3D IDs and GOA were significantly smaller than reported manufacturer sizes in the majority of the valve sizes. This RT-3D TEE-guided study provides ranges of reference values for directly measured IDs and GOA of the three most commonly used mechanical mitral prosthetic valve types for the first time in a relatively large series. WOS:000574796000001 2-s2.0-85091865163 PubMed: 33011903

Rheumatoid arthritis (RA) is a debilitating inflammatory condition characterised by joint damage that affects the cervical spine most commonly at the atlantoaxial joint resulting in neck pain and myelopathy. The pathogenesis of RA involves the formation of a hyperplastic synovial tissue, termed pannus, which invades the local bone and causes osseous erosion. Here, we describe a case of rapid onset quadriparesis due to spinal cord compression at C5-C6 secondary to vertebral subluxation and mass effect from a large inflammatory pannus in the subaxial spine. Surgical decompression and resection of the subaxial pannus were performed, and the patient regained strength in all extremities. Histopathologic evaluation of the resected tissue confirmed the diagnosis of pannus over other more common epidural masses. Pannus formation commonly occurs in the peri-odontoid region; however, its presentation as a large soft tissue mass in the subaxial spine is not described in the current literature. Therefore, pannus should be considered in the differential diagnosis of epidural masses in the spine of RA patients. We use this case to discuss the pathology and radiological findings relevant to rheumatoid pannus formation in the subaxial cervical spine, as well as emphasise the importance of treatment in the context to severe degenerative disease.

We present a 67-year-old woman who was hemodynamically stable with radiographic evidence of saddle pulmonary embolism (PE) in the main pulmonary artery and mobile thrombus in the right heart. Endovascular thrombectomy was scheduled under general anesthesia. Before anesthesia induction, femoral vessel access was planned under local anesthesia in case emergent cardiopulmonary bypass (CPB) was needed. Immediately after abdominal pannus retraction was applied for better groin access, the patient developed cardiac arrest, and advanced cardiovascular life support (ACLS) protocol was initiated. Transesophageal echocardiography (TEE) confirmed acute massive PE. CPB was emergently established. Surgical embolectomy was conducted with successful outcome.

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.

Background Pigs/bovines share common antigens with humans: α‐Gal, present in all pigs/bovines close to the human B‐antigen; and AH‐histo‐blood‐group antigen, identical to human AH‐antigen and present only in some animals. We investigate the possible impact of patients’ ABO blood group on bioprosthesis structural valve degeneration (SVD) through calcification/pannus/tears/perforations for patients ≤60 years at implantation. Methods and Results This was a single‐center study (Paris, France) that included all degenerative bioprostheses explanted between 1985 and 1998, mostly porcine bioprostheses (Carpentier‐Edwards second/third porcine bioprostheses) and some bovine bioprostheses. For the period 1998 to 2014, only porcine bioprostheses with longevity ≥13 years were included (total follow‐up ≥29 years). Except for blood groups, important predictive factors for SVD were prospectively collected (age at implantation/longevity/number/site/sex/SVD types) and analyzed using logistic regression. All variables were available for 500 explanted porcine bioprostheses. By multivariate analyses, the A group was associated with an increased risk of: tears (odds ratio[OR], 1.61; P =0.026); pannus (OR, 1.5; P =0.054), pannus with tears (OR, 1.73; P =0.037), and tendency for lower risk of: calcifications (OR, 0.63; P =0.087) or isolated calcification (OR, 0.67; P =0.17). A‐antigen was associated with lower risk of perforations (OR 0.56; P =0.087). B‐group patients had an increased risk of: perforations (OR, 1.73; P =0.043); having a pannus that was calcified (OR, 3.0, P =0.025). B‐antigen was associated with a propensity for calcifications in general (OR, 1.34; P =0.25). Conclusions Patient’s ABO blood group is associated with specific SVD types. We hypothesize that carbohydrate antigens, which may or may not be common to patient and animal bioprosthetic tissue, will determine a patient’s specific immunoreactivity with respect to xenograft tissue and thus bioprosthesis outcome in terms of SVD.

Some patients with a bileaflet mechanical heart valve (BMHV) show significant increases in the transvalvular pressure drop and abnormal leaflet motion due to a pannus (an abnormal fibrovascular tissue) formed on the ventricular side, even in the absence of physical contact between the pannus and leaflets. We investigate the effects of the pannus shape (circular or semi-circular ring), implantation location and height on the leaflet motion, flow structure and transvalvular pressure drop using numerical simulations. The valve model considered resembles a 25 mm masters HP valve. The mean systolic pressure drop is significantly increased with increasing pannus height, irrespective of its implantation orientation. Near the peak inflow rate, the flow behind the pannus becomes highly turbulent, and the transvalvular pressure drop is markedly increased by the pannus. At the end of valve opening and the start of valve closing, oscillatory motions of the leaflets occur due to periodic shedding of vortex rings behind the pannus, and their amplitudes become large with increasing pannus height. When the pannus shape is asymmetric (e.g., a semi-circular ring) and its height reaches about 0.1D (D (= 25 mm) is the diameter of an aorta), abnormal leaflet motions occur: two leaflets move asymmetrically, and valve closing is delayed in time or incomplete, which increases the regurgitation volume. The peak energy loss coefficients due to panni are obtained from simulation data and compared with those predicted by a one-dimensional model. The comparison indicates that the one-dimensional model is applicable for the BMHV with and without pannus.

Prosthetic valve thrombosis is a rare and severe complication of the mechanical prosthetic valve. Management can be challenging due to varying clinical presentation, overlapping features of differential diagnosis, and lack of randomized controlled trials on the therapeutic options. In this article, we report the case of a patient with a mechanical prosthetic mitral valve presented with symptoms of heart failure, and an echocardiography showing increased mean pressure gradient across the prosthesis along with a fixed posterior leaflet and a partially restricted anterior leaflet with no visible mass. That raised the concern for an obstructed prosthesis. After multimodality imaging and multidisciplinary team discussions, prosthetic valve thrombosis diagnosis was favored over other different diagnoses that included but not limited to pannus ingrowth. Fibrinolytic therapy was administrated, and the patient was discharged on optimal anticoagulation. Repeated echocardiography a month later showed normal mean gradient and normal functioning prosthetic mitral valve without the need for repeat mitral valve surgery.

BACKGROUND Recently, it has been shown that panniculectomy concurrent to living donor renal transplantation is a safe option for management of renal transplant recipients with a large focal pannus. This combined management requires precise coordination of teams. We describe the technique, timing, and sequence for combined renal transplantation and panniculectomy. METHODS We conducted a retrospective chart review of adult patients (≥18 years old) who underwent simultaneous living donor renal transplantation-panniculectomy from 2015 to 2019. A multi-team approach that included urology, transplant, and plastic surgery was used to perform the combined operations. Typically, the plastic surgery team initiates the operation by performing the panniculectomy. This is followed by kidney transplantation and graft anastomosis. The plastic surgery team then completes the operation with closure of the wound. RESULTS Twenty patients were identified. Most were male (12:8) with a mean age of 55 years and an average body mass index of 35 kg/m. The mean total operative duration was 394 minutes. On average, 17% of operating time was devoted to panniculectomy. At 90 days follow-up, there was 100% graft survival and all patients had primary graft function. There was a 25% wound complications rate and a 15% reoperation rate. CONCLUSION By performing panniculectomy first in the sequence, concurrent panniculectomy provides wide exposure and a large operative field for transplantation. Wound closure by plastic surgeons may mitigate the high complication rate commonly seen in obese patients with end-stage renal disease. Future studies are needed to evaluate the cost-benefit of the combined living donor renal transplantation-panniculectomy.

Background In the Solomon Islands and Vanuatu, the sign trachomatous inflammation—follicular (TF) is common, but ocular infection with Chlamydia trachomatis is not. It is therefore debatable whether azithromycin mass drug administration (MDA), the recommended antibiotic treatment strategy for trachoma’s elimination as a public health problem, is necessary in this setting. We set out to estimate what proportion of adolescents were at risk of progression of trachomatous scarring. Methods A cross-sectional survey was undertaken of all children aged 10–14 years resident in communities identified as high-TF clusters during previous population-based mapping. Graders examined children for clinical evidence of trachomatous scarring, pannus, and Herbert’s pits (HPs) or limbal follicles in both eyes. A dried blood spot was collected from each child and tested for antibodies to C. trachomatis. Results A total of 492 children in 24 villages of the Solomon Islands and Vanuatu were examined. In total, 35/492 (7%) of children had limbal signs (pannus and/or HPs) plus any conjunctival scarring. And 9/492 (2%) had limbal signs and moderate or severe conjunctival scarring; 22% of children were anti-Pgp3 seropositive. Conclusions Few adolescents here are at risk of future complications from trachoma, supporting the conclusion that further antibiotic MDA is not currently required for trachoma elimination purposes in these settings., In Solomon Islands and Vanuatu communities in which active trachoma prevalence in children was previously high, prevalence of Herbert’s pits or pannus plus conjunctival scarring in 10–14-year-olds is low, suggesting risk of future trachomatous blindness here is also low.

Purpose To describe the efficacy of autologous serum (AS) eye drops to reverse severe contact lens (CL)-induced limbal stem cell (LSC) deficiency (LSCD). Methods This is a prospective, uncontrolled, interventional case series that enrolled 20 eyes of 14 consecutive patients diagnosed with severe CL-induced LSCD at presentation, based on clinical examination, at a tertiary referral center for the period December 2016 to December 2018. All eyes underwent AS treatment for at least 2 weeks with a follow-up for at least 2 months. Demographic data and treatment outcomes were collected and analyzed. Results The mean patient age at presentation was 30.5 years (range, 19-49 years). The mean duration of soft contact lens wear was 15.6 years (SD, 7.58 years; range, 5-31 years). All study eyes had pain and blurred vision at presentation. All eyes had recurrent or persistent corneal epithelial defect, stromal scarring and opacity, and superficial vascularization and peripheral pannus at presentation. Aggressive treatment with AS succeeded in all eyes. Signs and symptoms of LSCD stabilized in all eyes within 2 weeks and resolved in 6 eyes (30.0%) in 2 weeks, 9 eyes (45.0%) in 4 weeks, and 5 eyes (25.0%) in 8 weeks. The mean follow-up time was 9.45 ± 1.79 weeks (range, 8-24 weeks). Conclusions Early identification and aggressive treatment of the ocular surface disease with AS can medically reverse severe CL-induced LSCD and prevent the need for surgical intervention.

Purpose of review A thorough understanding of the modes of bioprosthetic valve failure is critical as clinicians will be facing an increasing number of patients presenting with failed bioprostheses in coming years. The purpose of this article is to review modes of bioprosthestic valve degeneration, their management, and identify gaps for future research. Recent findings Guidelines recommend monitoring hemodynamic performance of prosthetic valves using serial echocardiograms to determine valve function and presence of valve degeneration. Modes of bioprosthetic valve failure may be categorized as structural degeneration (calcification, tears, fibrosis, flail), nonstructural degeneration (pannus), thrombosis, and endocarditis. Calcification is the most common form of structural valve degeneration. Predictors of bioprosthetic valve failure include valves implanted in the mitral position, younger age, and type of valve (porcine versus bovine pericardial). Failed bioprosthetic valves are managed with either redo surgical replacement or transcatheter valve-in-valve implantation. Summary Several modes of bioprosthetic valve failure exist, which vary based on patient, implant position, and valve characteristics. Further research is required to characterize factors associated with early failure to delay structural valve degeneration and improve patient prognosis.

Bioprosthetic valve thrombosis was previously considered to be a relatively rare complication of surgical or transcatheter bioprosthetic valve replacement. Although echocardiograms can reliably show the characteristic findings of prosthetic valve stenosis, differentiating between thrombus formation and pannus overgrowth as the underlying cause of prosthetic valve dysfunction can be challenging. We present the case of a 75-year-old man who underwent transthoracic Doppler echocardiography in the presence of an elevated valvular gradient 2 years after his aortic valve had been surgically replaced with a bioprosthesis. The echocardiographic findings suggested prosthetic valve stenosis. Cardiac computed tomography, performed to distinguish between thrombus formation and pannus overgrowth, revealed hypoattenuated leaflet thickening and reduced leaflet mobility, which suggested thrombus. After the patient took oral anticoagulants for 3 months, images showed complete resolution of the previous abnormalities, thus confirming the diagnosis of bioprosthetic valve thrombosis. We found cardiac computed tomography valuable when evaluating our patient who had an elevated prosthetic valve gradient.

Background This study aimed to evaluate the early and late clinical outcomes after repeat aortic valve replacement (AVR) for subaortic pannus in patients with mechanical valves. Methods and Results: Between 2001 and 2017, 51 patients (median age, 59 years; 42 women) with prosthetic aortic stenosis (AS) caused by pannus ingrowth underwent repeat AVR because of acute malfunction of monoleaflet valve (3 patients), severe prosthetic AS (30 patients), and moderate prosthetic AS at the time of tricuspid or mitral valve surgery (18 patients). The median follow-up duration was 100 (interquartile range, 64-138) months. Double valve replacement was performed in 45 (88%) patients. Median time interval from previous operation was 161 (interquartile range, 121-194) months. The explanted mechanical AV was monoleaflet and bileaflet in 16 (31%) and 34 (67%) patients, respectively. Concomitant procedures included 16 mitral valve replacements (14 repeat) and 36 tricuspid valve surgeries (15 replacements, 21 repairs). No hospital deaths or cases of heart block occurred. Overall survival and event-free survival rates at 10 years were 88% and 51%, respectively. Late complications included recurrent prosthetic AS (4 patients), new paravalvular leakage of the mitral valve (5 patients), and severe tricuspid regurgitation (2 patients). Conclusions Although repeat AVR for subaortic pannus had acceptable early and late survival, recurrent prosthetic AS was frequently observed during late follow-up.

Cervical disc arthroplasty (CDA) has received widespread attention as an alternative to anterior fusion due to its similar neurological and functional improvement, with the advantage of preservation of segmental motion. As CDA becomes more widely implemented, the potential for unexpected device-related adverse events may be identified.The authors report on a 48-year-old man who presented with progressive neurological deficits 3 years after 2-level CDA was performed. Imaging demonstrated periprosthetic osteolysis of the vertebral endplates at the CDA levels, with a heterogeneously enhancing ventral epidural mass compressing the spinal cord. Diagnostic workup for infectious and neoplastic processes was negative. The presumptive diagnosis was an inflammatory pannus formation secondary to abnormal motion at the CDA levels. Posterior cervical decompression and instrumented fusion was performed without removal of the arthroplasty devices or the ventral epidural mass. Postoperative imaging at 2 months demonstrated complete resolution of the compressive pannus, with associated improvement in clinical symptoms. Follow-up MRI at > 6 months showed no recurrence of the pannus. At 1 year postoperatively, CT scanning revealed improvement in periprosthetic osteolysis.Inflammatory pannus formation may be an unexpected complication of abnormal segmental motion after CDA. This rare etiology of an epidural mass associated with an arthroplasty device should be considered, in addition to workup for other potential infectious or neoplastic mass lesions. In symptomatic individuals, compressive pannus lesions can be effectively treated with fusion across the involved segment without removal of the device.