Fluid-structure interaction and structural simulation of high acceleration effects on surgical repaired human mitral valve biomechanics.

Mitral valve dynamics depend on force stability in the mitral leaflets, the mitral annulus, the chordae tendineae, and the papillary muscles. In chordal rupture conditions, the proper function of the valve disrupts, causing mitral regurgitation, the most prevalent valvular disease. In this study, Structural and FSI frameworks were employed to study valve dynamics in healthy, pathologic, and repaired states. Anisotropic, non-linear, hyper-elastic material properties applied to tissues of the valve while the first-order Ogden model reflected the best compatibility with the empirical data. Hemodynamic blood pressure of the cardiovascular system is applied on the leaflets as uniform loads varying by time, and exposure to high acceleration loads imposed on models. Immersed boundary method used for simulation of fluid in a cardiac cycle. In comparison between healthy and pathologic models, stress values and chordal tensions are increased, by nearly threefold and twofold, respectively. Stress concentration on leaflets is reduced by 75% after performing a successful surgical repair on the pathological model. Crash acceleration loads led to more significant stress and chordae tension on models, by 27% and 23%, respectively. It is concluded that a more sophisticated model could lead to a better understanding of human heart valve biomechanics in various conditions. If a preoperative plan is developed based on these modeling methods, the requirement for multiple successive repairs would be eliminated, operative times are shortened, and patient outcomes are improved.

Hyperpigmented Mycosis Fungoides Masquerading as Longstanding Lichen Planus Pigmentosus: A Diagnostic Pitfall.

BACKGROUND: Mycosis fungoides (MF) is a rare primary cutaneous T-cell lymphoma, accounting for 50%-60% of all cutaneous T-cell lymphoma cases. It has a prevalence of approximately 5-6 cases per 1 million people annually and a higher incidence in dark-skinned populations. CASE PRESENTATION: We report a case of hyperpigmented MF in a 72-year-old dark-skinned man with a 5-year history of progressive, widespread poikilodermatous patches and thin plaques on the back and bilateral legs. The patient had been treated for lichen planus pigmentosus for 5 years without significant response to therapy. ASSESSMENT: Multiple biopsies revealed a band-like lymphoid infiltrate in the dermis, accompanied by intraepidermal lymphocytes, some of which had larger hyperchromatic nuclei. CD4 + T lymphocytes were predominant over CD8 + T-positive cells located along the epidermis, dermoepidermal junction, and in the dermis. DIAGNOSIS: A diagnosis of hyperpigmented MF was made based on the clinical, histopathological, and immunohistochemical findings. CONCLUSION: This case report highlights the importance of considering hyperpigmented MF as a differential diagnosis in patients with longstanding lichen planus pigmentosus, particularly when there is a lack of response to therapy.

Current status and prospects for the diagnosis of pemphigus vulgaris.

Introduction: Pemphigus vulgaris (PV) is an intraepidermal autoimmune bullous disease (AIBD) characterized by autoantibodies against desmosomal adhesion proteins, most commonly desmoglein (Dsg)3, leading to the suprabasal cleft formation and acantholysis.Areas covered: Direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) studies display the intercellular deposition of IgG/C3 throughout the epidermis and presence of circulating autoantibodies respectively, as a net-like pattern. However, the target antigen remains unknown using immunofluorescence techniques. Thanks to the development of Dsg ELISA, using recombinant technology, circulating antibodies against Dsg1 and 3 could be detected sensitively. It is possible to differentiate PV from pemphigus foliaceus (PF) using this assay. BIOCHIP mosaic and multivariant ELISA are two novel serologic methods with the added value of the ability to screen several AIBDs simultaneously.Non-Dsg1/3 antigens are also involved in the pathogenesis of PV and investigated more deeply thanks to the protein microarrays technique. Additionally, patients with high values of anti-Dsg1/3 may be lesion-free, suggesting the presence of nonpathogenic autoantibodies.Expert opinion: Newer diagnostic methods to replace traditional techniques should possess high sensitivity and specificity and be widely available, noninvasive, and relatively cheap. The newly developed methods need to be further evaluated before being recommended for routine use.

An experimental study of nonlinear rate-dependent behaviour of skeletal muscle to obtain passive mechanical properties.

Accurate modelling of biological tissues has been a significant need for analysis of the human body. In this article, a comprehensive in vitro experimental study has been done on the fresh bovine skeletal muscle before the onset of rigour mortis in order to provide an experimental description of passive skeletal muscle properties in three dimensions. Different situations including various deformation modes, different loading rates and loading directions are tested to consider all features of skeletal muscle behaviour. Based on the nonlinear continuum mechanics, a three-dimensional visco-hyperelastic model is introduced which considers all aspects of skeletal muscle's features such as nonlinear hyperelastic, time-dependent behaviour, anisotropy and quasi-incompressibility. Visco-hyperelastic material constants are obtained for passive behaviour of the muscle based on genetic algorithm optimization method via comparing the theoretical and experimental results. Experiments show that the rate of loading affects the configuration of experimental curves considerably. It could be also concluded that compression-tension asymmetry, as well as anisotropic behaviour, of the muscle is due to fibres orientation. Obtained experimental results help to achieve a better understanding of mechanical properties and nonlinear behaviour of the skeletal muscles.

Grover Disease With Epidermal Dysmaturation Pattern: A Common Histopathologic Finding.

BACKGROUND: Grover disease is an entity whose diagnosis is based on clinicopathologic correlation. Histopathologically, focal acantholysis is the most common finding. In some cases, there is prominent squamous atypia which can prove to be very challenging and the lesion may be confused with an epidermal neoplasm. OBJECTIVE: To report on atypical histopathological changes in Grover disease and to provide helpful clues to differentiate between the epidermal atypia seen in some cases of Grover disease and epithelial neoplasms. MATERIAL AND METHODS: We analyzed 33 cases of Grover disease histologically diagnosed at Wake Forest Baptist Medical Center, NC, between 2011 and 2017. Atypical changes in keratinocytes were defined as epithelial buds, nuclear pleomorphism, and dyskeratosis in all layers of epidermis or altered granular layer. RESULTS: Twenty cases (64%) showed foci with alteration of the normal keratinocytic maturation, whereas 18 cases demonstrated nuclear pleomorphism. Buds of epithelial cells emanating from the basal layer of the epidermis and granular cell alteration was present in 19 cases. CONCLUSIONS: The findings especially the presence of an altered granular layer may represent a diagnostic clue in cases of Grover disease with atypical changes.

Sebaceous carcinoma in situ as a concept and diagnostic entity.

Although carcinoma in situ has been accepted as a well-established concept and diagnostic category, for reasons unknown sebaceous carcinoma in situ has not been recognized yet in general pathology or dermatopathology. Such lesions have always been misinterpreted as either benign neoplasm or sebaceous carcinoma. In the present essay, we provide a convincing account supporting sebaceous carcinoma in situ as a valid concept and diagnostic entity via critical literature review and histopathological assessment and illustration. Recognizing sebaceous carcinoma in situ as a valid concept and diagnostic entity will certainly help to avoid misinterpretation and subsequently under or over treatment of such lesions.

Correlation of Antiglobulin Reactivity and Severity of Pancytopenia in a Patient with Hemophagocytic Lymphohistiocytosis: A Case Report and Review of Literature.

A 46­year­old obese male with a medical history of thalassemia minor presented to the emergency room with complaints of severe fatigue and jaundice worsening over two weeks. On further evaluation, the patient was found to have significant hyperbilirubinemia and transaminitis. The hospital course was further complicated by pancytopenia requiring multiple transfusions, worsening hyperbilirubinemia, severe hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia. He was also found to have splenomegaly and evidence of hemophagocytosis on bone marrow biopsy. On further testing, the patient was also found to have evidence of hemolysis along with a positive direct Coomb's test consistent with autoimmune hemolytic anemia (AIHA), and elevated soluble IL-2 receptor level. The patient was subsequently diagnosed with hemophagocytic lymphohistiocytosis (HLH). He was treated with HLH-94 protocol along with rituximab for AIHA which resulted in improvement of patient's condition. We present a case of HLH with no prior history of autoimmune disease, associated with Coomb's positive AIHA that resolved after therapy for HLH. Our case also delineates how the intensity of antiglobulin reactivity, if present, may correlate with severity of the disease, its progression, and response to treatment.

Pigmented perivascular epithelioid cell tumor of the skin: first case report.

The authors present a first case of pigmented perivascular epithelioid cell tumor (PEComa) of the skin, which was misdiagnosed histopathologically as metastatic melanoma. PEComa are exceedingly rare neoplasms, and only a few cases have been reported in kidney, liver, and pelvis. Herein, we describe this very rare entity in the subcutaneous tissue of the flank with very similar if not identical morphology of renal clear cell carcinoma. Because of the presence of focal melanin pigmentation and strong positivity for HMB-45, the lesion was mistaken for metastatic melanoma. To the best of authors' knowledge, this is the first case of cutaneous PEComa with melanin pigmentation. Awareness about occurrence of the lesion in the subcutaneous tissue and its unique immunoprofile would be helpful to reach correct diagnosis and to distinguish this lesion from melanoma or metastatic renal clear cell carcinoma.

Papillary adenocarcinoma in situ of the skin: report of four cases.

Although rare isolated cases of adenocarcinoma in situ of skin have been reported in the literature, adenocarcinoma in situ of skin as a concept and as a diagnostic category has not been established in the field of dermatopathology. In this work, four cases of papillary adenocarcinoma in situ of the skin are presented. In addition, the notion that lesions previously reported in the medical literature under the term of "papillary eccrine adenoma" are actually adenocarcinoma in situ is discussed.

A Unique Case of Malignant Pleuropericardial Effusion: HHV-8-Unrelated PEL-Like Lymphoma-A Case Report and Review of the Literature.

Primary effusion lymphoma (PEL) or body cavity lymphoma is a rare type of extra nodal lymphoma of B-cell origin that presents as lymphomatous effusion(s) without any nodal enlargement or tumor masses. It belongs to the group of AIDS related non-Hodgkin's lymphomas. First described in 1996 in HIV infected individuals who were coinfected with Kaposi's sarcoma-associated herpesvirus (KSHV) or HHV-8 virus, it was included as a separate entity in WHO classification of tumors of hematopoietic and lymphoid tissue in the year 2001. The definition included association with HHV-8 virus as a mandatory diagnostic criterion. However, cases were later reported where PEL-like disease process was diagnosed in HHV-8 negative patients. This was eventually recognized as a rare but distinct entity termed as "HHV-8-unrelated PEL-like lymphoma". Herein, we are reporting a case of an elderly patient who presented with a large pleuropericardial effusion and was eventually diagnosed with this entity. Till date, only around 50 cases of HHV-8-unrelated PEL-like lymphoma have been reported and our case being EBV, HIV, and Hepatitis C negative makes it very unique and rare occurrence. We are also presenting a review of relevant literature focused mainly on comparing outcomes in patients treated with and without chemotherapy.

A study assessing the feasibility and diagnostic accuracy of real-time teledermatopathology.

Dermatopathology represents the gold standard for the diagnosis of skin diseases and neoplasms that cannot be diagnosed on clinical grounds alone. The aim of this study was to test the feasibility and to assess the accuracy of an Internet-based real-time (live) teledermatopathology consultation. Twenty teaching cases and 10 randomly selected routine cases were presented to four expert dermatopathologists, first by real-time teledermatopathology and, subsequently, in a blinded fashion, using light microscopy. Throughout the study the overall diagnostic accuracy did not differ for the two methods. However, the mean level of confidence and the mean observation times differed significantly between real-time teledermatopathology and light microscopy (92.6±0.24% versus 99.5±0.02%, and 96.31±11.55 sec versus 25.47±3.85 sec, respectively). Assessment of routine cases did not produce significant diagnostic differences between the two methods. These results prove that real-time teledermatopathology offers an affordable and technically simple technology that lends itself to training as well as to diagnosis of lesions from routine practice by experts situated at remote sites.

Feasibility and diagnostic agreement in teledermatopathology using a virtual slide system.

We investigated the feasibility and diagnostic agreement of a virtual slide system (VSS) in teledermatopathology. Forty-six biopsy specimens from inflammatory skin diseases were selected and scanned with a VSS at the Research Unit of Teledermatology, Medical University of Graz, Graz, Austria. Images were stored on a virtual slide server on which a specific Web application suited for telepathology (http://telederm.org/research/dermatopath/) runs. Twelve teleconsultants from 6 different countries reviewed the 46 cases, working directly on the Web application. Telediagnoses agreed with gold standard and conventional diagnosis with an average of 73% and 74%, respectively. Complete concordance among all teleconsultants with gold standard and conventional diagnosis was found in 20% of the cases. In 10 cases in which complete clinical data were missing, the average agreement of telediagnosis with gold standard diagnosis and conventional diagnosis decreased to 65% and 66%, respectively. Only 3 of 4 cases of inflammatory skin diseases were correctly diagnosed remotely with VSS. The system that we have used, despite its usability, is not completely feasible for teledermatopathology of inflammatory skin disease. Moreover, the performance seems to have been influenced by the availability of complete clinical data and by the intrinsic difficulty of the pathology of inflammatory skin diseases.