The Associations of Aortic Valve Sclerosis, Aortic Annular Increased Reflectivity, and Mitral Annular Calcification with Subsequent Aortic Stenosis in Older Individuals: Findings from the Cardiovascular Health Study.

BACKGROUND: Although aortic valve sclerosis (AVS) is well described as preceding aortic stenosis (AS), the associations of AS with antecedent mitral annular calcification (MAC) and aortic annular increased reflectivity (AAIR) have not been characterized. In a population-based prospective study, the authors evaluated whether MAC, AAIR, and AVS are associated with the risk for incident AS. METHODS: Among participants of the Cardiovascular Health Study free of AS at the 1994-1995 visit, the presence of MAC, AAIR, AVS, and the combination of all three was evaluated in 3,041 participants. Cox proportional-hazards regression was used to assess the association between the presence of calcification and the incidence of moderate or severe AS in three nested models adjusting for factors associated with atherosclerosis and inflammation both relevant to the pathogenesis of AS. RESULTS: Over a median follow-up period of 11.5 years (interquartile range, 6.7-17.0 years), 110 cases of incident moderate or severe AS were ascertained. Strong positive associations with incident moderate or severe AS were found for all calcification sites after adjustment for the main model covariates: AAIR (hazard ratio [HR], 2.90; 95% CI, 1.95-4.32; P < .0005), AVS (HR, 2.20; 95% CI, 1.44-3.37; P < .0005), MAC (HR, 1.67; 95% CI, 1.14-2.45; P = .008), and the combination of all three (HR, 2.50; 95% CI, 1.65-3.78; P < .0005). In a secondary analysis, the risk for AS increased with the number of sites at which calcification was present. CONCLUSIONS: In a large cohort of community-dwelling elderly individuals, there were strong associations between each of AAIR, AVS, MAC, and the combination of the three and incident moderate or severe AS. The novel finding that AAIR had a particularly strong association with incident AS, even after adjusting for other calcification sites, suggests its value in identifying individuals at risk for AS and potential inclusion in routine assessment by transthoracic echocardiography.

MicroRNAs miR-629-3p, miR-1202 and miR-1225-5p as potential diagnostic and surgery outcome biomarkers for mesial temporal lobe epilepsy with hippocampal sclerosis.

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) is a symptomatic epilepsy syndrome clinically characterized by high prevalence, pharmacoresistance, good surgical prognosis and hippocampal sclerosis (HS); however, no singular criteria can be considered sufficient for the MTLE-HS diagnosis. MicroRNAs (miRNAs) are small non-coding molecules that act as important gene-expression regulators at post-transcriptional level. Evidences on the involvement of miRNAs in epilepsy pathogenesis as well as their potential to be employed as biomarkers claim for investigations on miRNAs' applicability as epilepsy diagnosis and prognosis biomarkers. Consequently, the present study aimed to evaluate the applicability of three specific miRNAs as biomarkers of diagnosis and surgical outcomes in adult patients with MTLE-HS. METHOD: Hippocampus, amygdala and blood samples from 20 patients with MTLE-HS were analyzed, 10 with favorable surgical prognosis (Engel I) and 10 with unfavorable surgical prognosis (Engel III-IV). For the control groups, hippocampus and amygdala from necropsy and blood samples from healthy individuals were adopted. The miRNAs expression analysis was performed using Real-Time Quantitative Polymerase Chain Reaction for miRNAs highlighted from microarray as being involved in GABAergic neurotransmission. RESULTS: The miRNAs miR-629-3p, miR-1202 and miR-1225-5p were found to be hyper-expressed in MTLE-HS patients' blood. CONCLUSIONS: Our data suggest the existence of three circulating miRNAs (miR-629-3p, miR-1202 and miR-1225-5p) that could possibly act as additional tools in the set of factors that contribute to MTLE-HS diagnose.

[Mediastinal pseudotumor-necrotizing and sclerosing mediastinitis with pseudomembranes]. / Mediastinaler Pseudotumor ­ nekrotisierende und sklerosierende Mediastinitis mit Pseudomembranen.

Mediastinal tumors present a rather rare phenomenon with a variety of underlying causes. Important differential diagnoses include benign and malignant tumors as well as idiopathic sclerosing mediastinitis and parasitic infection.Here, we present the case of a mediastinal pseudotumor with compression of the superior vena cava in a young adult male who spent several years abroad in Brazil. Clinicians suspected either a mediastinal lymphoma, malignant mesenchymal tumor, teratoma, sarcoidosis, or tuberculosis. Biopsy tissue failed to provide a definite diagnosis. The subsequently resected mediastinal mass showed a necrotizing, granulomatous inflammation with prominent eosinophilia and sclerosis. Membranous structures were detected in the necrotic areas, which presented as collagen bundles ultrastructurally. Therefore, these membranes were proven to be constituents of lipid pseudomembranes. Consequently the lesion shows characteristics of sclerosing mediastinitis next to characteristics of adipose tissue necrosis with lipid pseudomembranes. Parasitic infection could not be proven.

Mesangial sclerosis in a patient with type 1 diabetes following simultaneous pancreas-kidney transplantation despite maintenance of normoglycemia: a case report.

BACKGROUND: Simultaneous pancreas-kidney transplantation is considered a curative treatment for type 1 diabetes complicated by end-stage kidney disease. We report herein a case of mesangial sclerosis in a patient who underwent successful kidney-pancreas transplantation despite well-controlled glucose and excellent pancreatic allograft function. CASE PRESENTATION: A 76-year-old type 1 diabetic man who underwent a simultaneous pancreas-kidney transplantation 19 years prior presented with persistent nephrotic range proteinuria although creatinine was at his baseline (normal) level. Hemoglobin A1c and fasting glucose were well controlled without the use of insulin or oral antihyperglycemic agents. Serum lipase and amylase were within the reference range and there was no evidence of donor-specific antibodies. Kidney allograft biopsy was performed to evaluate proteinuria and showed diffuse capillary loop thickening and diffuse moderate to severe mesangial sclerosis resembling diabetic nephropathy. CONCLUSIONS: This case demonstrates a case of mesangial sclerosis resembling diabetic nephropathy in a patient with good glucose control after simultaneous pancreas-kidney transplantation with excellent pancreatic allograft function.

Case Report: Idiopathic Sclerosing Orbital Inflammation.

SIGNIFICANCE: Idiopathic sclerosing orbital inflammation (ISOI) is characterized by insidious, chronic, progressive inflammation and fibrosis that damage ocular structures and produce a mass effect. This case highlights the challenges in diagnosis and management of ISOI, as well as the associated ocular morbidities, including potential vision loss. PURPOSE: The purpose of this study was to provide education regarding a rare condition that exhibits variable presentation and has an unpredictable success rate with regard to treatment paradigm. Improved therapeutic options are promising. Ultimately, early detection and management are key and may allow for better visual outcome. CASE REPORT: A 46-year-old woman presented with complaints of chronic right-sided facial headaches and eye pain and gradual right globe prominence over the previous 6 months. Worsening vision and decreased right peripheral visual field were also noted. Upon examination, an afferent pupillary defect and florid disc edema were evident. Imaging studies revealed an orbital and extraorbital infiltrative mass involving the right orbital apex, inferior orbital fissure, pterygopalatine fossa, and cavernous sinus. Right anterior orbitotomy with biopsy revealed fragments of fibroconnective and adipose tissue with sclerosis and chronic focal inflammation, consistent with ISOI. Treatment included intravenous methylprednisone, followed by oral prednisone, beginning at 60 mg/d with a slow taper thereafter. Signs and symptoms improved dramatically and eventually resolved. Vision significantly improved, and the afferent pupillary defect resolved. The patient remained asymptomatic at 3-month follow-up. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is difficult to diagnose and manage. No large studies exist because of the rare nature of the disease. Slowly progressive, nonspecific signs and symptoms may delay recognition and treatment. Orbital imaging and histopathologic analysis are critical for definitive diagnosis. Conventional treatment with corticosteroids is not uniformly successful, but newer combined therapy options can improve outcomes. Early identification and treatment are key to management and ultimate preservation of function and vision.

Fibrosing Mediastinitis Associated With Tuberculosis in Children.

Two children developed fibrosing mediastinitis following past tuberculosis disease. Both were microbiologically negative for tuberculosis at presentation. One was treated with steroids and supportive therapy, but developed active tuberculosis with complications. He ultimately succumbed to healthcare-associated infection. The other recovered with steroids, administered along with antituberculosis treatment.

Ptosis and Miosis Associated with Fibrosing Mediastinitis.

BACKGROUND Fibrosing mediastinitis is a rarely seen, progressive disease. It results from an excessive fibrotic reaction in the mediastinum. We describe a presentation of fibrosing mediastinitis that, to our knowledge, has never been seen before. CASE REPORT A 30-year-old female Colombian flight attendant presented with a right eyelid droop. Examination revealed partial right-sided ptosis and miosis but no anhidrosis. An ill-defined firm swelling was palpable at the root of the neck. Chest radiography revealed a widened mediastinum, and computerized tomography (CT) showed a right paratracheal mass without calcification extending to the thoracic inlet, encasing multiple blood vessels. All basic blood tests, magnetic resonance imaging of the head, and ultrasound Doppler of the neck vessels were normal. History and work up for infections including fungal diseases, granulomatous diseases, vasculitis, and autoimmune diseases were negative. Positron emission tomography (PET) showed significant FDG uptake in the mediastinum. Mediastinal biopsy was histologically consistent with fibrosing mediastinitis. All relevant immunohistochemistry and microbiological studies were negative. Subsequently, the patient developed signs of superior vena cava compression; this was managed by balloon angioplasty, which resulted in improvement of symptoms. However, over time, her symptoms worsened progressively, resulting in a left-sided ptosis and radiological progression of the mass on CT. She received treatment with rituximab and concomitant steroids, which yielded excellent results: the treatment led to both resolution of her symptoms and regression of the mass and its metabolic activity on PET scan. CONCLUSIONS Fibrosing mediastinitis can present with an incomplete Horner's syndrome. Treatment with rituximab and steroids shows promising results in select cases of metabolically active idiopathic fibrosing mediastinitis.

Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies.

Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n = 26), TLE due to hippocampal sclerosis (n = 14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n = 11). TLE patients showed increased proportions of human leukocyte antigen-DR isotype (HLA-DR)-expressing CD4+ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14low CD16+ cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR-expressing CD8+ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.

Computer-assisted Diagnosis of Breast Cancer by Cell Network Matrix Extraction and Multilayer Perceptron Analysis.

OBJECTIVE: Diagnosis of breast cancer is based on identification of various morphologic features by histopathologic examination of the specimen. Ancillary immunohistochemical and molecular analyses provide additional information that is prognostic and guides therapy. Because of subjectivity in this approach, we sought to develop a computer model which could assist in differentiating normal or benign tissue from malignant breast carcinoma. METHODS: Cases of benign sclerosing adenosis (20) and high-grade invasive ductal carcinomas (20) of breast were retrieved and re-examined. Five images of the diagnostic areas from each case were captured (400x). Each image was divided into quadrants and saved as 1-megapixel each. These 800 images were then binarized and segmented using the watershed method. The cell graphs were extracted to identify the matrix of adjacent cells and the network properties were determined for each image. The local network features were fed into a PAM model and global network features were fed into a multilayer perceptrons (MLP) to distinguish between benign and malignant samples. These characteristics were evaluated by training the models on 40% (320) of the randomly assigned images followed by real-time testing of the remaining 60% (480) images. In addition, normal breast tissue from five cases was retrieved and forty (40) images were captured to further test the model. RESULTS: Both local and global network feature models had high area under the curve (AUC) (0.63 and 0.99 respectively), with their adjusted Rand indices (ARI) being 0.61 and 0.87, respectively. Pooling the pseudoprobabilities of the two neural networks greatly increased the accuracy of the model with predictions of the combined model at image level being 100% accurate with AUC of 1. CONCLUSION: This study shows that using a combination of cell-graph extraction and a deep learning algorithm computers can accurately distinguish between benign and malignant breast lesions.

Superior vena cava stenting in IgG4-associated mediastinal fibrosis.

We report a rare case of IgG4-associated mediastinal fibrosis with complete superior vena cava (SVC) obstruction successfully managed by thrombolysis and stenting in a 33-year-old male. The patient presented with a mediastinal mass lesion with clinical findings of SVC obstruction. Surgical biopsy of the mediastinal mass lesion with histology and immunohistochemistry staining established the diagnosis of IgG4 associated mediastinal fibrosis. The patient was treated with a systemic steroid and rituximab, but despite treatment, SVC obstruction and thromboses persisted, surgical intervention was declined by the thoracic surgeon due to extensive mediastinal fibrosis and an expected poor outcome. Percutaneous SVC angioplasty, intravascular thrombolysis with tissue plasminogen activator and afterward stent placement was done by the interventional radiology service. This intervention is rare and possibly was lifesaving as it restored complete patency of the SVC. Our case is probably the first with IgG4 mediastinitis and SVC complete obstruction relieved by intravascular thrombolysis and SVC stent placement. It demonstrates that SVC stenting can relieve SVC obstruction in patients with a high risk of surgery either due to medical comorbidities or an expected high surgical risk like bleeding in the mediastinal fibrosis, which in our case of SVC obstruction was due to a nonoperable mediastinal tumor. SIMILAR CASES PUBLISHED: None to our knowledge.

Ultrasound characteristics of sclerosing adenosis mimicking breast carcinoma.

BACKGROUND: Sclerosing adenosis (SA) is a benign lesion with complicated pathological components and could mimic breast carcinoma in both clinical palpation and medical imaging findings. The present study was conducted to assess the value of ultrasound (US) characteristics in diagnosing SA and their differentiation from breast carcinoma. METHODS: We retrospectively reviewed the medical records of 305 women (347 lesions) with invasive ductal carcinoma (IDC) and 54 women with single SA lesion, who had breast excision between April 2016 and July 2018. US BI-RADS atlas and elastography were applied and their associated characteristics were compared between SA and IDC. RESULTS: The mean age of SA was younger than that of IDC (43.6 ± 7.4 vs 53.2 ± 10.3, P < 0.001). Compared to IDC, SA had more frequency of parallel orientation (94.44% vs 71.76%, P < 0.001) and circumscribed margin (48.15% vs 4.90%, P < 0.001), less frequency of irregular shape (64.81% vs 95.97%, P < 0.001), hypoechoic echotexture (88.89% vs 98.27%, P = 0.002), calcification (12.96% vs 55.04%, P < 0.001), and posterior acoustic changes (3.70% vs 53.89%, P < 0.001) or associated features (architectural distortion, 3.70% vs 59.65%, P < 0.001; duct changes, 18.52% vs 63.40%, P < 0.001). Vascularity absence was more common in SA compared to IDC (35.19% vs 6.63%, P < 0.001). And the elasticity score was lower in SA (2.38 ± 0.60 vs 3.91 ± 0.81, P < 0.001). After adjusting for age, we found spiculated margin, posterior shadowing, calcification, architectural distortion, and vascularity could independently identify the differences between these two entities. After involving elasticity score, the calcification and vascularity could still be independent indicators for differential diagnosis. CONCLUSION: Understanding SA imaging features will enable radiologists to communicate results to the referring physician consistently, which could benefit a reliable assessment and specific management recommendations. A systematic evaluation of the US BI-RADS atlas together with breast elastography may be a powerful tool to identify SA and differentiate it from breast cancer.

Multicentric B-cell lymphoma with presumed paraneoplastic generalized cutaneous sclerosis in a dog.

BACKGROUND: Reports of dermal sclerosis in dogs include scleroderma or morphea of unknown cause, cicatricial alopecia and congenital/hereditary fibrosis. CLINICAL SUMMARY: A 12-year-old, male castrated chihuahua-mix dog was evaluated for skin lesions of unknown duration. The dog had severe alopecia, skin thickening and marked peripheral lymphadenopathy. Lymph node cytological investigation, immunohistochemical investigation and clonality testing demonstrated an intermediate to large B-cell lymphoma. The thickened skin had severe collagen deposition, effacing adnexal structures. The dog's lymphoma was treated but the skin lesions remained unchanged. The dog was euthanized. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of multicentric B-cell lymphoma in a dog with concurrent diffuse cutaneous sclerosis, similar to a human paraneoplastic reaction.

Increased IgG4-positive plasma cells in nodular-sclerosing Hodgkin lymphoma: a diagnostic pitfall.

AIMS: Despite increasing interest in the recently established immunoglobulin 4-related disease (IgG4-RD), its pathogenesis and aetiology remain largely unclear. Characteristic histopathological features are one of the key elements of diagnosis, including 'storiform' fibrosis, obliterative phlebitis, increased lymphoplasmacytic infiltration and increased levels of IgG4 in serum and tissue. Histopathological features of IgG4-RD are striking but not specific, and can pose a pitfall for surgical pathologists. This paper aims to determine the actual amount of IgG4+ plasma cells in nodular-sclerosing Hodgkin lymphoma (NSHL) and its potential to be misdiagnosed in routine clinical practice. METHODS AND RESULTS: IgG4+ plasma cells per high-power field (HPF) and the ratio of IgG4+ versus IgG+ plasma cells (IgG4/IgG ratio) in lymph node biopsies of 24 patients with nodular-sclerosing Hodgkin lymphoma (NSHL) were determined using immunohistochemistry and consensus scoring criteria as used for IgG4-RD. Ten lymph node biopsies with reactive follicular hyperplasia were assessed for comparison. Higher numbers of IgG4+ plasma cells (P < 0.001) were observed in NSHL versus follicular hyperplasia (mean 34 versus 8 per HPF) with a mean IgG4/IgG ratio of 0.38 versus 0.18. Five cases (21%) fulfilled the consensus criteria of IgG4-RD, with >50 IgG4+ plasma cells per HPF and an IgG4/IgG ratio of >0.4. The mean count of IgG4+ plasma cells per HPF in NSHL varied greatly (3-88) with increased numbers of IgG4+ plasma cells seen near areas of fibrosclerosis. CONCLUSIONS: Significantly higher levels of IgG4+ plasma cells are common in NSHL, emphasising the need to exclude Reed-Sternberg cells by morphology and immunohistochemistry in biopsies where IgG4-RD is suspected.

A review of endovascular stenting for superior vena cava syndrome in fibrosing mediastinitis.

Fibrosing mediastinitis (FM) is a rare disorder of inflammation and fibrosis involving the mediastinum. The formation of fibroinflammatory mass in the mediastinum can lead to obstruction of mediastinal structures and cause severe debilitating and life-threatening symptoms. Superior vena cava syndrome (SVCS) is a dreaded complication of FM with no medical therapy proven to be efficacious. Spiral vein grafting has long been utilized as first-line therapy for SVC syndrome due to FM. Endovascular repair with stents and angioplasty for malignant causes of SVC syndrome is well established. However, there are limited data on their utility in SVC syndrome due to FM. We present two cases of SVC syndrome due to FM treated with endovascular stenting and a detailed review of current literature on its utility in SVCS due to benign causes.

Sclerosing peritonitis presenting as complete mechanical bowel obstruction: a case report.

INTRODUCTION: Sclerosing peritonitis or abdominal cocoon syndrome is characterized by small bowel loops completely encapsulated by a fibrocollagenous membrane in the center of the abdomen. Although cocooning of the abdomen is mostly seen in patients on peritoneal dialysis, it can occur de novo; it very rarely manifests as complete mechanical bowel obstruction. CASE PRESENTATION: A 46-year-old Asian man presented with complete mechanical bowel obstruction. He had previous attacks of partial bowel obstruction during the past 6 to 8 months, which was misdiagnosed as abdominal tuberculosis because tuberculosis is very prevalent in the region in which he lives. He took anti-tuberculosis therapy for 3 months but this did not result in resolution of his symptoms. This time he had diagnostic laparoscopy followed by laparotomy in which a fibrocollagenous membrane, resulting in entrapment of his bowel, was excised and his entire small bowel was freed. Postoperatively he again had a mild episode of partial bowel obstruction but this was relieved with a short course of steroids. DISCUSSION: Sclerosing peritonitis is a rare benign etiology of complete mechanical bowel obstruction. Patients might have suffered recurrent attacks of partial bowel obstruction in the past that were falsely managed on lines of other conditions such as tuberculosis, especially in endemic areas like Pakistan or India. CONCLUSION: Sclerosing peritonitis is a rare benign diagnosis which can manifest as complete bowel obstruction and a high index of suspicion is required to diagnose it. Contrast-enhanced computed tomography of the abdomen is a useful radiological tool to aid in preoperative diagnosis. Diagnostic laparoscopy is usually confirmatory. Peritoneal sac excision and adhesiolysis is the treatment and a short course of steroids in relapsing symptoms.