[Left Ventricular Outflow Tract Obstruction After Transcatheter Aortic Valve Replacement due to Pannus Formation].

We experienced a case of surgical aortic valve re-replacement due to structural valve deterioration caused by pannus formation 4 years after transcatheter aortic valve replacement( TAVR). The patient underwent surgery because the mean transvalvular pressure gradient increased to 48 mmHg on echocardiography. Contrast-enhanced computed tomography (CT) was useful for predicting the site of adhesion to surrounding tissue preoperatively and exploring the presence of the pannus. Intraoperative findings showed the TAVR valve was covered with neointima except around the origins of the left and right coronary arteries and was firmly adhered to the surrounding tissues. As residual pannus was present in the subvalvular tissues, it was carefully removed. The explanted TAVR valve functioned well with good opening and closure. The postoperative course was uneventful. Pannus formation can result from mechanical stress. TAVR valves put significantly greater stress on the left ventricular outflow tract than surgical valves and may be more likely to cause pannus formation.

A Radiographic Abdominal Pannus Sign is Associated With Postoperative Complications in Anterior THA.

BACKGROUND: Numerous studies have shown that elevated BMI is associated with adverse outcomes in THA; however, BMI alone does not adequately represent a patient's adipose and soft tissue distribution, especially when the direct-anterior approach is evaluated. Local soft tissue and adipose, especially in the peri-incisional region, has an unknown impact on patient outcomes after direct-anterior THA. Moreover, there is currently no known evaluation method to estimate the quantity of local soft tissue and adipose tissue. The current study introduced a new radiographic parameter that is measurable on supine AP radiographs: the abdominal pannus sign. QUESTION/PURPOSE: Are patients who have an abdominal pannus extending below the upper (cephalad) border of the symphysis pubis more likely to experience problems after anterior-approach THA that are plausibly associated with that finding, including infections resulting in readmission, wound complications resulting in readmission, fractures, or longer surgical time, than patients who do not demonstrate this radiographic sign? METHODS: Between 2015 and 2020, five surgeons performed 727 primary direct-anterior THAs. After exclusion criteria were applied, 596 procedures were included. Of those, we obtained postoperative radiographs in the postanesthesia care unit in 100% of procedures (596 of 596), and 100% of radiographs (596) were adequate for review in this retrospective study. The level of the pannus in relation to the pubic symphysis was assessed on immediate supine postoperative AP radiographs of the pelvis: above (pannus sign 1), between the upper and lower borders (pannus sign 2), or below the level of the pubic symphysis (pannus sign 3). In this study, we combined pannus signs 2 and 3 into a single group for analysis not only because there was a limited number of patients in each group, but also because there was no statistically significant difference between the two groups. Pannus sign 1 was identified in 82% of procedures (486 of 596), and pannus sign ≥ 2 was identified in 18% (110). We compared the groups (pannus sign 1 versus pannus sign ≥ 2) in terms of the percentage of patients who experienced problems within 90 days of THA that might be associated with that physical finding, including infections resulting in readmission including subcutaneous, subfascial, and prosthetic joint infections; wound complications resulting in readmission, defined as dehiscence or delayed healing; and all fractures, and we compared the groups in terms of surgical time-that is, the cut-to-close time. RESULTS: Patients with a pannus sign of ≥ 2 were more likely than those with a pannus sign of 1 to have a postoperative infection (6.4% [seven of 110 procedures] versus 0.6% [three of 486], odds ratio 10.96 [95% confidence interval (CI) 2.83 to 42.38]; p < 0.01), wound complications (0.9% [one of 110] versus 0% [0 of 486] with an infinite odds ratio [95% CI indeterminate]; p = 0.18), and fractures (4.5% [five of 110] versus 0% [0 of 486], with an infinite odds ratio [95% CI indeterminate]; p < 0.01). The mean surgical time was longer in patients with a pannus sign of ≥ 2 than it was in those with a pannus sign of 1 (128 ± 25.3 minutes versus 118 ± 27.5 minutes, mean difference 10 minutes; p < 0.01). CONCLUSION: Based on these findings, patients who have an abdominal pannus that extends below the upper (cephalad) edge of the pubic symphysis are at an increased risk of experiencing serious surgical complications. If THA is planned in these patients, an approach other than the direct-anterior approach should be considered. Surgeons performing THA who do not obtain supine radiographs preoperatively should use a physical examination to evaluate for this finding, and if it is present, they should use an approach other than the direct-anterior approach to minimize the risk of these complications. Future studies might compare the abdominal pannus sign using standing radiographs, which are used more often, with other well-documented associated risk factors such as elevated BMI or higher American Society of Anesthesiologists classification. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Incidence and Risk Factors of Pannus after Mechanical Aortic Valve Replacement.

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.

Conjunctival Scarring, Corneal Pannus, and Herbert's Pits in Adolescent Children in Trachoma-endemic Populations of the Solomon Islands and Vanuatu.

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.

Dysfunctioning mechanical mitral valve prosthesis: When thrombus over pannus makes hinders diagnosis.

Prosthetic valve obstruction is a rare but potentially lethal complication. The most frequent causes are thrombus and pannus formation, in the absence of infectious data. Diagnosis is not always easy using cardiac CT scanning and in 46%-85% of cases thrombus and pannus coexist, complicating the diagnosis. A rapid diagnosis is essential to avoid a fatal outcome of this pathology whose mortality, despite correct treatment, is high.

Biological Response to Sintered Titanium in Left Ventricular Assist Devices: Pseudoneointima, Neointima, and Pannus.

Titanium alloys have traditionally been used in blood-contacting cardiovascular devices, including left ventricular assist devices (LVADs). However, titanium surfaces are susceptible to adverse coagulation, leading to thrombogenesis and stroke. To improve hemocompatibility, LVAD manufacturers introduced powder sintering on blood-wetted surfaces in the 1980s to induce endothelialization. This technique has been employed in multiple contemporary LVADs on the pump housing, as well as the interior and exterior of the inflow cannula. Despite the wide adoption of sintered titanium, reported biologic response over the past several decades has been highly variable and apparently unpredictable-including combinations of neointima, pseudoneoimtima, thrombus, and pannus. We present a history of sintered titanium used in LVAD, a review of accumulated clinical outcomes, and a synopsis of gross appearance and composition of various depositions found clinically and in animal studies, which is unfortunately confounded by the variability and inconsistency in terminology. Therefore, this review endeavors to introduce a unified taxonomy to harmonize published observations of biologic response to sintered titanium in LVADs. From these data, we are able to deduce the natural history of the biologic response to sintered titanium, toward development of a deterministic model of the genesis of a hemocompatible neointima.

Acute Pulmonary Embolism Caused by Abdominal Pannus Retraction in an Awake Patient in the Operating Room: A Case Report.

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.

Rheumatoid pannus presenting as a large epidural mass in the subaxial cervical spine: A case report.

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.

Operative Technique for Resection of a Ventral Transdural Retro-Odontoid Pannus: A 2-Dimensional Operative Video.

BACKGROUND: Retro-odontoid pseudotumors are rare inflammatory complications of atlantoaxial instability often associated with cervical degenerative disease and rheumatoid arthritis. While propagation of these lesions has been shown to cause spinal cord compression and cervical myelopathy, intradural extension has rarely been reported. METHODS: In this manuscript and 2-dimensional illustrative intraoperative video, we demonstrate cervical decompression, removal of the intradural component, and stabilization with C1-2 instrumentation using a posterior approach. A 71-year-old patient presented with progressive cervical myelopathy. Preoperative imaging demonstrated a large retro-odontoid pannus causing severe spinal cord compression and an associated contrast-enhancing intradural lesion, in the absence of obvious C1-2 instability or fractures on computed tomography scan. C1-2 posterior decompression and fusion were performed with maximally safe intradural pannus resection and ventral dural reconstruction. RESULTS: Postoperatively, the patient experienced significant improvement in myelopathic symptoms. Imaging demonstrated good spinal cord decompression with complete intradural pannus resection and debulking of the extradural component. CONCLUSIONS: Our outcome in this rare complication suggests a posterior approach may be effective in treating similar patients.

Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis.

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.

Influence of Tissue Technology on Pannus Formation on Bioprosthetic Heart Valves.

PURPOSE: Bioprosthetic heart valves have several modes of failure. Tissue degeneration and calcification are the major modes of failure with the highest focus of attention, however pannus formation can also be problematic. We studied the effect of a new tissue technology with the absence of any glutaraldehyde-based storage solution and a stable aldehyde capping process on pannus formation. METHODS: Using a juvenile sheep model of mitral valve replacement, valves with the new tissue technology were compared to control valves with contemporary bovine pericardial tissue, regarding pannus formation. Valves were implanted for either a 5- or 8-month period. Explanted valves were examined macroscopically and histologically. Histological observations were made by an independent pathologist, blinded to group identity. RESULTS: Pannus area measured macroscopically on the test valves was significantly lower than the pannus on the control tissue. This was confirmed on the histological samples, where the total pannus overgrowth was significantly lower in the test group compared to the control. CONCLUSION: The new tissue technology leads to less pannus formation. This may beneficially influence both short- and long-term valve behavior of bioprosthetic valves.

Updating the pathophysiology of arthritic bone destruction: identifying and visualizing pathological osteoclasts in pannus.

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

Pannus-related left main trunk ostial stenosis after aortic valve replacement.

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.

The protein-protein interaction between connective tissue growth factor and annexin A2 is relevant to pannus formation in rheumatoid arthritis.

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.

[Bileaflet mechanical valve dysfunction related to fibrous pannus: the role of cine-fluoroscopy]. / Disfunzione di protesi valvolare meccanica bileaflet da panno fibroso: non dimenticare la cine-fluoroscopia!

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.

Resolvin D1 suppresses pannus formation via decreasing connective tissue growth factor caused by upregulation of miRNA-146a-5p in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint stiffness, finally leading to tissue destruction. Connective tissue growth factor (CTGF) is a critical factor in RA progression, which promotes fibroblast-like synoviocyte (FLS) proliferation, pannus formation, and the damage of cartilage as well as bone. Resolvin D1 (RvD1) can promote inflammation resolution in acute inflammatory diseases, and recently, effects of RvD1 on chronic inflammatory diseases also attracted attention. This study aimed to examine the effect of RvD1 on pannus formation in RA and the underlying mechanism. METHODS: Serum levels of RvD1 and CTGF were determined in RA patients and healthy persons by UPLC-MS/MS and ELISA respectively. The levels of CTGF and inflammatory factors were assessed by qRT-PCR and ELISA. MicroRNA expression profile was determined by miRNA microarray. The effects of CTGF, RvD1, and miR-146a-5p on angiogenesis were evaluated with tube formation and chick chorioallantoic membrane (CAM) assays. Collagen-induced arthritis (CIA) mice were constructed to detect the effects of RvD1 and miR146a-5p on RA. STAT3 activation was determined by Western blotting. RESULTS: RvD1 levels decreased while CTGF levels increased in RA patients' serum, and an inverse correlation of the concentrations of RvD1 and CTGF in the serum of RA patients was synchronously observed. In CIA mice, RvD1 suppressed angiopoiesis and decreased the expression of CTGF. Simultaneously, RvD1 significantly decreased CTGF and pro-inflammation cytokines levels in RA FLS. Furthermore, CTGF suppressed angiopoiesis and RvD1 inhibited the proliferation and migration of RA FLS and angiopoiesis. MiRNA microarray and qRT-PCR results showed that RvD1 upregulated miRNA-146a-5p. The transfection experiments demonstrated that miRNA-146a-5p could decrease inflammatory factors and CTGF levels. Moreover, miRNA-146a-5p decreased the proliferation of FLS and angiogenesis in vivo. MiRNA-146a-5p also suppressed angiogenesis and downregulated the expression of CTGF in CIA mice. Finally, Western blot results revealed that miRNA-146a-5p inhibited the activation of STAT3. CONCLUSION: RvD1 is prone to alleviate RA progression through the upregulation of miRNA-146a-5p to suppress the expression of CTGF and inflammatory mediators, thereby decreasing pannus formation and cartilage damage.