The 100 most impactful articles in foot and ankle surgery: An altmetric analysis.

Citation count and impact factor of the publishing journal are two historically utilized metrics to determine an article's impact in its research field. However, these metrics are limited given the rise in research dissemination through social media. Across other orthopedic specialties, the Altmetric Attention Score (AAS) has been used to determine which articles are most impactful.

Lupus anticoagulant hypoprothrombinemia syndrome: A case report.

Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare entity associated with an increased risk of hemorrhage. Corticosteroids have been used in its treatment with favorable results. We present the case of a 54-year-old female patient with a personal history of Lupus diagnosed with LAHPS following an episode of cerebellar hemorrhage.

Lipid nanoparticles for cyclosporine A administration: development, characterization, and in vitro evaluation of their immunosuppression activity.

Cyclosporine A (CsA) is an immunosuppressant commonly used in transplantation for prevention of organ rejection as well as in the treatment of several autoimmune disorders. Although commercial formulations are available, they have some stability, bioavailability, and toxicity related problems. Some of these issues are associated with the drug or excipients and others with the dosage forms.

Focal High-intensity Focused Ultrasound Targeted Hemiablation for Unilateral Prostate Cancer: A Prospective Evaluation of Oncologic and Functional Outcomes.

Background: In selected patients with unilateral, organ-confined prostate cancer (PCa), hemiablation of the affected lobe might be feasible to achieve acceptable cancer control with fewer complications.

Objectives: To assess the oncologic and functional outcomes of focal high-intensity focused ultrasound (HIFU) hemiablation in unilateral organ-confined PCa.

Design, Setting And Patients: Single-center prospective evaluation of HIFU hemiablation for unilateral organ-confined PCa was performed from July 2009 through December 2013.

GDF5 regulates TGFß-dependent angiogenesis in breast carcinoma MCF-7 cells: in vitro and in vivo control by anti-TGFß peptides.

Background: TGFß overproduction in cancer cells is one of the main characteristics of late tumor progression being implicated in metastasis, tumor growth, angiogenesis and immune response. We investigated the therapeutic efficacy of anti-TGFß peptides in the control of angiogenesis elicited by conditional over-expression of TGFß.

Methods: We have inserted in human MCF7 mammary-cancer cells a mutated TGFß gene in a tetracycline-repressible vector to obtain conditional expression of mature TGFß upon transient transfection, evaluated the signaling pathways involved in TGFß-dependent endothelial cells activation and the efficacy of anti-TGFß peptides in the control of MCF7-TGFß-dependent angiogenesis.

Systemic sclerosis endothelial cells recruit and activate dermal fibroblasts by induction of a connective tissue growth factor (CCN2)/transforming growth factor β-dependent mesenchymal-to-mesenchymal transition.

Objective: Clinical evidence suggests that the vascular abnormalities of systemic sclerosis (SSc) precede the onset of fibrosis, but molecular cues accounting for a possible vascular connection of SSc fibrosis have been elusive, although they have been searched for intensively. Since we had previously shown that connective tissue growth factor (CCN2), endowed with fibroblast-oriented activities, was overexpressed by endothelial cells (ECs) from SSc patients, we undertook this study to investigate its role and mechanisms in fibroblast activation.

Methods: Normal fibroblasts were challenged with conditioned medium of normal microvascular ECs (MVECs) and MVECs obtained from SSc patients with the diffuse form of the disease.

Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation.

Background: Interleukin-8 (IL-8, CXCL8) is readily produced by human malignant cells. Dendritic cells (DC) both produce IL-8 and express the IL-8 functional receptors CXCR1 and CXCR2. Most human colon carcinomas produce IL-8.

Therapeutic effect of a peptide inhibitor of TGF-β on pulmonary fibrosis.

Pulmonary fibrosis encompasses several respiratory diseases characterized by epithelial cell injury, inflammation and fibrosis. Transforming growth factor (TGF)-β1 is one of the main profibrogenic cytokines involved in the pathogenesis of lung fibrosis. It induces fibroblast differentiation into myofibroblasts, which produce high levels of collagen and concomitantly loss of lung elasticity and reduction of the respiratory function.

Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression.

Melanoma progression is associated with the expression of different growth factors, cytokines, and chemokines. Because TGFβ1 is a pleiotropic cytokine involved not only in physiologic processes but also in cancer development, we analyzed in A375 human melanoma cells, the effect of TGFβ1 on monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) expression, two known factors responsible for melanoma progression. TGFβ1 increased the expression of MCP-1 and IL-10 in A375 cells, an effect mediated by the cross-talk between Smad, PI3K (phosphoinositide 3-kinase)/AKT, and BRAF-MAPK (mitogen activated protein kinase) signaling pathways.

Corneal descriptive indices in the fellow eye of unilateral keratoconus.

Objectives: To determine whether indices derived from corneal topography could be used to differentiate between three populations at varying degrees of risk for presenting keratoconus, but otherwise unremarkable clinical appearance.

Methods: Eighty subjects lacking clinical signs of keratoconus were divided into three groups according to their background. Fifty refractive surgery candidates were used as controls, to be compared with 15 clinically normal fellow eyes of subjects with unilateral keratoconus, and 15 eyes from first and second degree relatives of the former keratoconic patients.

Novel pharmacologic strategies to protect the liver from ischemia-reperfusion injury.

Ischemia and reperfusion (I/R) injury develops when blood flow is interrupted for a long period of time and then restarted. In the liver, this type of damage occurs in clinical settings such as liver transplantation and hepatic resection. Given the shortage of donor organs it is essential to maximize the use of sub-optimal organs, those previously rejected due to elevated risk of malfunction, and to increase split-liver transplantation interventions.

Identification of peptide inhibitors of transforming growth factor beta 1 using a phage-displayed peptide library.

Pathologies such as liver fibrosis and scleroderma are characterized by harmful levels of transforming growth factor beta 1 (TGFbeta1). These levels could be neutralized if inhibitors of this cytokine were available. With this aim we searched for peptides with binding affinity for TGFbeta1 using a phage-displayed random 15-mer peptide library.

Analysis of results related to good and bad outcomes of Intacs implantation for keratoconus correction.

Purpose: To evaluate factors influencing good and poor outcomes after intracorneal ring segment implantation to correct keratoconus.

Setting: Instituto Oftalmológico de Alicante (Vissum Corporation), University of Miguel Hernandez, Alicante, Spain.

Methods: A retrospective comparative study of the visual outcome, 25 eyes of 21 patients were implanted after intracorneal ring segments (Intacs, Addition Technology) as a method to correct keratoconus.

Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8.

In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of (111)In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas.

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

Purpose: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity.

Patients And Methods: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study.

Improving efficacy of interleukin-12-transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens.

Intralesional administration of cultured dendritic cells (DCs) engineered to produce IL-12 by in vitro infection with recombinant adenovirus frequently displays eradicating efficacy against established subcutaneous tumors derived from the CT26 murine colon carcinoma cell line. The elicited response is mainly mediated by cytolytic T lymphocytes. In order to search for strategies that would enhance the efficacy of the therapeutic procedure against less immunogenic tumors, we moved onto malignancies derived from the inoculation of MC38 colon cancer cells that are less prone to undergo complete regression upon a single intratumoral injection of IL-12-secreting DCs.

Anti-ICAM-2 monoclonal antibody synergizes with intratumor gene transfer of interleukin-12 inhibiting activation-induced T-cell death.

Purpose: Systemic treatment with an anti-ICAM-2 monoclonal antibody (mAb; EOL4G8) eradicates certain established mouse tumors through a mechanism dependent on the potentiation of a CTL-mediated response. However, well-established tumors derived from the MC38 colon carcinoma cell line were largely refractory to this treatment as well as to intratumor injection of a recombinant adenovirus encoding interleukin-12 (IL-12; AdCMVIL-12). We sought to design combined therapy strategies with AdCMVIL-12 plus anti-ICAM-2 mAbs and to identify their mechanism of action.

Clinical implications of antigen transfer mechanisms from malignant to dendritic cells. exploiting cross-priming.

Expansion and activation of cytolytic T lymphocytes bearing high-affinity T-cell receptors specific for tumor antigens is a major goal of active cancer immunotherapy. Physiologically, T cells receive promitotic and activating signals from endogenous professional antigen-presenting cells (APC) rather than directly from malignant cells. This phenomenon fits with the broader concept of cross-presentation that earlier was demonstrated for minor histocompatibility and viral antigens.

Heat-shock protein 70-1 and HLA class II gene polymorphisms associated with celiac disease susceptibility in Navarra (Spain).

Heat shock proteins (HSP) are thought to play a role in the immune response making probable their contribution to celiac disease (CD). We studied the polymorphisms in the 5' regulatory region of the HSP70-1 gene and performed genomic HLA-DQ and -DR typing in 128 CD patients and 94 healthy controls from Navarra (Spain). The frequency of the C allele of the HSP70-1, characterized by the intermediate electrophoretic mobility of DNA, was significantly increased among CD patients (64.

Secretion of neu differentiation factor-like polypeptides by cph-transformed fibroblasts: cloning and characterization of Syrian hamster neuregulin cDNAs.

We reported previously that expression of the cph oncogene in Syrian hamster and mouse cells leads to the secretion of a polypeptide factor or factors structurally and functionally related to neu differentiation factor (NDF) and the establishment of an autocrine loop mediated through the simultaneous overexpression of the erbB4 receptor. To identify the nature of this factor and to characterize its role in the neoplastic conversion of Syrian hamster embryo cells, we cloned cDNAs hybridizing to rat NDF-derived probes by screening a library prepared from neoplastic 81C39 cells, which harbor an activated cph oncogene and secrete active NDF-like polypeptides. Sequence analysis of the isolated clones revealed a high level of homology between the hamster neuregulin and its rat and human counterparts and the existence of various neuregulin cDNA variants in Syrian hamster cells, presumably originating from alternatively spliced RNA species.

Immune complexes from HIV-1+ patients contain infectious virus able to infect normal lymphocytes.

It has been suggested that circulating immune complexes containing HIV-1 could be involved in enhancement of the infection through Fc receptors. To test this hypothesis, immune complexes precipitated from the sera of 25 HIV-1-seropositive individuals, at different stages of the disease, were assayed for the presence of infectious virus. When added to phytohemagglutinin-activated peripheral blood lymphocytes, seven of 25 complexes were able to sustain a productive infection.

Anti-CD4 activity in circulating immune complexes in HIV-infected patients.

Levels of circulating immune complexes (CIC) measured by precipitation with 1.04 M ammonium sulfate ranged from 22 to 2,040 micrograms/ml in a group of 141 HIV-infected patients. CIC were elevated (> 200 micrograms/ml) in 72.

DNA content in non-Hodgkin's lymphoma. Comparison between flow cytometry and cytogenetics in fresh and paraffin-embedded tissue.

DNA content of 36-non-Hodgkin's lymphomas was analyzed by flow cytometry (FCM) and cytogenetics (CG), 21 in fresh and 15 in paraffin-embedded tissue. The results of both techniques were coincident in 60% of the fresh tissue samples and in 45% of the paraffin-embedded ones, the reason for this difference could be the poor resolution of DNA histograms from paraffin-embedded tissue. All samples judged as aneuploid by FCM were aneuploid also by CG.

Levamisole and interferon in children with chronic hepatitis B.

To evaluate the possible usefulness of simultaneous administration of levamisole and interferon, we randomly allocated 38 children with chronic hepatitis B to receive either 10 MU/m2 interferon-alpha-2a, three times a week for 6 mo (group 1, n = 20) or 90 mg/m2 of levamisole for 45 days, together with 10 MU/m2 of interferon-alpha-2a, three times a week for 6 mo (group 2, n = 18). At the end of the follow-up period (15 mo), no significant differences were observed between the groups with respect to loss of hepatitis B virus DNA and HBeAg from serum and normalization of serum ALT levels. During therapy, a significant increase in the serum levels of ALT and soluble interleukin-2 receptor was observed in both groups but was higher in patients from group 2.