Systematic skin examination in an acute geriatric unit: skin cancer prevalence.

BACKGROUND: Ageing is a determining factor in skin cancer, but the incidence and prevalence of skin cancer in elderly patients are not known. AIM: To determine the prevalence of skin cancers in elderly patients and to assess their associated geriatric syndromes. METHODS: Between January and April 2013, all consecutive incident patients hospitalized in the Acute Geriatric Unit of Lille University Hospital underwent a geriatric assessment and a systematic dermatological examination. A biopsy was taken whenever there was any lesion with suspicion of malignancy. RESULTS: In total, 204 patients (mean age 85.4 years) were included, and 16 cutaneous biopsies were taken from 15 patients. Histological examination confirmed skin cancer in 11 biopsies from 10 patients: 9 basal cell carcinomas, 1 squamous cell carcinoma (SCC) and 1 malignant lentigo. The prevalence of skin cancer was 4.9%. The geriatric assessment revealed severe geriatric syndromes in the 10 patients with skin cancer: severe dependence (8/10), possible cognitive impairment (10/10), and moderate or severe malnutrition (5/10). CONCLUSIONS: The prevalence of skin cancer is high in frail elderly patients. The association of severe geriatric syndromes suggests that close collaboration between geriatricians and dermatologists is essential to optimize the treatment of skin carcinoma in elderly patients.

Anti-sRAGE autoimmunity in obesity: downturn after bariatric surgery is independent of previous diabetic status.

AIM: Morbid obesity increases the risk of cardiovascular disease (CVD). The receptor for advanced glycation end-products (RAGE) is implicated in proinflammatory processes that underlie CVD. Its soluble form (sRAGE) has been proposed as a vascular biomarker. Recently, anti-sRAGE autoantibodies were described and found to be increased in diseases where RAGE is overexpressed. This study aimed to investigate serum levels of anti-sRAGE autoantibodies in morbidly obese patients. METHODS: After exclusion based on specific criteria, 150 subjects (50 normoglycemics, 50 glucose-intolerants and 50 diabetics) were randomly recruited from a cohort of 750 obese patients (ABOS). Serum sRAGE and anti-sRAGE autoantibodies were measured before bariatric surgery. Sixty-nine patients were followed for up to 1year after gastric bypass, and their levels of sRAGE and anti-sRAGE autoantibodies measured. The control group consisted of healthy blood donors. RESULTS: Compared with controls, baseline levels of sRAGE and anti-sRAGE autoantibodies were significantly higher in all obese patients independently of glucose regulation (P<0.001). At 1year after gastric bypass, sRAGE and anti-sRAGE were decreased (P<0.001). The decrease in anti-sRAGE autoantibodies was correlated with an increase in high-density lipoprotein (HDL; P=0.02). CONCLUSION: Independently of previous diabetic status, morbid obesity increases sRAGE and anti-sRAGE levels. Weight loss after gastric bypass is followed by a decrease in both titres. The decrease in anti-sRAGE correlates with an increase in HDL.

Human immunodeficiency virus-associated thrombotic microangiopathies: clinical characteristics and outcome according to ADAMTS13 activity.

Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case-control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS13 <5% HIV(+) group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13 >or=5% HIV(+) group). HIV(+) patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS13 <5% idiopathic group) or without (17 patients, ADAMTS13 >or=5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS13 <5% HIV(+) patients had less AIDS-related complications than ADAMTS13 >or=5% HIV(+) patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4(+) T cell count was higher (P = 0.05). TMA-associated death rate was higher in ADAMTS13 >or=5% HIV(+) patients than in ADAMTS13 <5% HIV(+) patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS13 <5% patients, TMA-associated death rate was comparable between HIV(+) and idiopathic patients (15.5% in idiopathic patients, P-value was non-significant). By contrast, TMA-associated death rate in ADAMTS13 >or=5% HIV(+) patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV-associated TMA with severe ADAMTS13 deficiency have less AIDS-related complications and a higher CD4(+) T cell count. TMA prognosis is better and comparable to this of idiopathic forms.

Human herpesvirus-8 (HHV-8)-associated primary effusion lymphoma in two renal transplant recipients receiving rapamycin.

The Akt/mammalian target of rapamycin (mTOR) signaling cascade has been demonstrated to be constitutively activated in several malignancies, including Kaposi sarcoma (KS) and human herpesvirus-8 (HHV-8)-associated primary effusion lymphoma (PEL). In organ transplant recipients, therapeutic change from cyclosporin to the mTOR inhibitor rapamycin can lead to regression of KS lesions. Recent experiments using PEL cell lines and murine xenograft PEL models suggested that rapamycin could inhibit the growth of PEL cells. In the present report, we describe the cases of two HIV-1-negative males of African origin who underwent renal transplantation and developed PEL while receiving rapamycin as immunosuppressive treatment. Both patients were retrospectively found to be HHV-8 seropositive before renal transplantation. The present case report suggests that rapamycin may not protect HHV-8-infected renal transplant recipients from occurrence of PEL or progression of pre-existing PEL.

Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation.

Advanced glycation end-products (AGEs) inhibit ischemia-induced angiogenesis but are potential triggers of neoangiogenesis that occurs in peritoneal dialysis (PD) patients. We investigated whether the effect of glucose and AGEs on human peritoneal mesothelial cells (HPMCs) might alter the release of vascular endothelial growth factor (VEGF) and subsequently the formation of capillary tubes by human umbilical vein endothelial cells (HUVECs). HPMCs were exposed to glucose and the glycated protein Nvarepsilon-(carboxymethyl)lysine-human serum albumin (CML-HSA) and VEGF production was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Capillary tube formation by HUVECs in presence of HPMC supernatant or co-cultured with HPMC was investigated. AGE and VEGF levels in PD effluents from 11 patients were measured. CML-HSA stimulated VEGF production by HPMCs, P<0.001. Glucose and AGE inhibited capillary tube formation by HUVECs, P<0.001. HPMC supernatant potentiated capillary tube formation, P<0.001. In co-culture with HPMC capillary tube formation was increased, especially by HPMCs stimulated by CML-HSA, P<0.001. Anti-VEGF antibody limited this effect, P<0.001. Preincubation of HPMCs with anti-receptor for AGEs (RAGE) antibody reduced capillary tube formation, P<0.001. AGE and VEGF levels in PD effluents were increased during long dwell time, P<0.05 and P<0.001, respectively. In a co-culture system, we showed that VEGF production by HPMC favors capillary tube formation through mesothelial RAGE activation and could explain neoangiogenesis in PD patient.

Postprandial hyperglycemia alters inflammatory and hemostatic parameters.

Glucose or glucose derived products are increased in blood during the postprandial phase and are, to a certain extent, related to meal composition. Glucose and glucose derived products such as advanced glycation end products (AGEs) can be formed in the intracellular compartment but can also be absorbed as AGEs or AGE precursors present in food. Glucose, glucose metabolites and AGEs alter endothelial cell functions, induce adhesion molecule overexpression (ICAM-1, VCAM), cytokine release (IL-6, MCP-1) and tissue factor production. Tumor necrosis factor alpha systemic level is increased during the postprandial phase as are augmented C reactive protein and fibrinogen level. Hyperglycemia induced an increase in plasminogen activator inhibitor, and shortened fibrinogen half life. Hyperglycemia and AGEs provoked an oxidant stress. The formation of reactive oxygen intermediates perturbates NO (Nitric oxide) formation and are deleterious for cell functions. All the modifications observed in the postprandial phase are not too deleterious but their iterative characteristics may lead to vascular dysfunction.

[Human herpes virus 8: molecules determinants of oncogenesis and modulation of the immune response]. / Herpèsvirus humain 8: bases moléculaires de l'oncogenèse et de la modulation de la réponse immunitaire.

Human herpesvirus 8 (HHV8), also called Kaposi sarcoma-associated herpesvirus (KSHV), is a human c2-herpesvirus, characterized by B lymphotropism and oncogenic properties. HHV8 is the etiological agent of Kaposi sarcoma, and of rare B cell lymphoproliferative disorders mostly observed in immunocompromised hosts (patients with AIDS, transplant organ recipients) such as primary effusion lymphoma and the plasma cell variant of multicentric Castleman disease. HHV8 contains numerous open reading frames encoding homologs to cellular genes involved in cell growth and apoptosis control. Among these are signal-transducing transmembrane proteins, secreted cytokine and chemokine homologs, transcriptional modulators, cell cycle regulators and apoptosis inhibitors. Several immune modulation strategies are used by HHV8 to target both innate and adaptative immunity, including complement activity control, Th2 chemotaxis, inhibition of type I and II interferons and B cell receptor signalling, and downregulation of class I histocompatibility antigens.

Loss of the ex vivo but not the reinducible CD8+ T-cell response to Tax in human T-cell leukemia virus type 1-infected patients with adult T-cell leukemia/lymphoma.

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after in vitro restimulation. To better understand this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all the ATLL patients, we found that mitogenic activation allowed the induction of CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce IFNgamma in response to Tax peptides. In contrast, only a minority of the patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These findings indicate that although a restimulatable anti-HTLV-1 CTL activity persists during ATLL, the specific ex vivo response is not constantly maintained. This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is affected by ATLL development and reveals that a major defect concerns the generation and/or the functionality of CD8+ effectors.

Diffuse large B-cell non-Hodgkin's lymphoma in a patient with autoimmune lymphoproliferative syndrome.

Mutations of Fas or Fas ligand genes result in the autoimmune lymphoproliferative syndrome (ALPS) in humans. We report here a diffuse large B-cell non-Hodgkin's lymphoma occurring in a man with ALPS. Fas-mediated lymphocyte apoptosis was defective in vitro, owing to a mutation within the death domain of the Fas molecule. High-dose methotrexate and doxorubicin-based chemotherapy led to complete remission of lymphoma.

A clinical, molecular and cytogenetic study of 12 cases of human herpesvirus 8 associated primary effusion lymphoma in HIV-infected patients.

INTRODUCTION: Primary effusion lymphoma is a rare type of B-cell lymphoproliferative disorder which is mainly observed in patients with HIV infection. Lymphomatous cells bridge features of immunoblastic and anaplastic cells with a non-B non-T phenotype and are characterized by the presence of the human herpesvirus 8 genome. We report on the retrospective analysis of 12 cases. PATIENTS AND METHODS: : Twelve HIV-infected patients with serous effusions containing large HHV8(+) lymphomatous cells were extensively evaluated to disclose associated visceral involvement. Clonality was assessed by IgH gene rearrangement PCR analysis (n = 11) or Southern blot (n = 1). EBV and HHV8 DNA sequences were detected by PCR analysis. Cytogenetics studies were performed in seven cases using RHG-banding. RESULTS: Extraserous localizations of lymphoma were present in six cases (50%): mediastinal (n = 2), mesenteric (n = 2), pancreatic (n = 1), and bone marrow involvement (n = 1). A monoclonal rearrangement of IgH genes was demonstrated in six cases, an oligoclonal pattern in one, whereas no clonality could be detected in five. High HHV8 copy numbers were demonstrated in all effusion fluids, with EBV-co-infection in all cases but one. Cytogenetic analysis displayed a complex karyotype in all cases without recurrent abnormalities. Eight patients have died. Three patients are in complete remission at 28, 53 and 55 months after high-dose chemotherapy (n = 1), cidofovir and alpha-interferon combination therapy (n = 1), and antiretroviral therapy alone (n = 1). CONCLUSION: The clinical and molecular pattern, as well as the response to therapy suggest that primary effusion lymphoma represents an heterogenous type of virus-induced B-cell lymphoproliferative disorder, sharing pathophysiological features with that induced by the Epstein-Barr virus and occurring in immunocompromised patients.

High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric castleman disease in HIV-infected patients.

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin-6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with human herpesvirus 8 (HHV8) infection. In a prospective study of 23 HIV-infected patients with MCD, clinical symptoms of MCD were present at 45 visits, whereas patients were in chemotherapy-induced clinical remission at 50 visits. Symptoms were associated with a high level of serum C reactive protein, high HHV8 viral load in peripheral blood mononuclear cells, and high plasma human IL-6 and IL-10 levels. Strong correlations between plasma IL-6 and plasma IL-10 with the HHV8 viral load suggest that both cytokines may be involved in the pathogenesis of this virus-associated lymphoproliferative disorder.

[Muscle infarction. An unknown complication of diabetes mellitus]. / L'infarctus musculaire. Une complication méconnue du diabète.

INTRODUCTION: Diabetic muscle infarction (MI) is a rare and little-known complication of diabetes mellitus. CASE REPORT: We report a case of relapsing MI in which magnetic resonance imaging (MRI) suggested the diagnosis. A 53-year-old man with multi-complicated type II diabetes mellitus was admitted to our unit for illness and deep tumefaction of the right thigh. Because of unconclusive MRI, a muscular biopsy of the lesion was performed and MI confirmed. Three months after, a left relapse of MI occurred. Immediate treatment with immobilization and heparinotherapy permitted a rapid recovery. CONCLUSION: About 70 previously reported cases are reviewed. The mean age at presentation was about 40 years. MI was usually seen in patients with long-standing diabetes with multiple end organ microvascular complications. Homo- or heterolateral recurrences are reported in almost half of the patients. MRI is the best imaging technique for suggesting the diagnosis.

[Human herpesvirus 8 (HHV8). II. Pathogenic role and sensitivity to antiviral drugs]. / L'herpèsvirus humain 8 (HHV8). II. Rôle pathogène et sensibilité aux antiviraux.

Human herpesvirus 8 (HHV8) has been found to be associated with three different diseases observed in Aids patients: Kaposi's sarcoma, primary effusion lymphoma, which is a rare type of non-Hodgkin lymphomas affecting the body cavities, and multicentric Castleman's disease. The role of this new herpesvirus and other lymphoid proliferations, like angioimmunoblastic lymphadenopathy or multiple myeloma, is much debatable. To date, there are several evidences for a direct role of this virus in the occurrence of the Kaposi's sarcoma, although the hypothesis of a passenger virus hypothesis cannot be totally excluded. In vitro, HHV8 is sensitive to some anti-herpesvirus drugs like foscarnet, cidofovir and adefovir, but the indications of these therapies in the prevention or the treatment of the Kaposi's sarcoma have not been documented so far.

[Human herpesvirus 8 ( HHV-8 ): I. Characteristics and epidemiology]. / L'herpèsvirus humain 8 (HHV8): I. Caractérisation et épidémiologie.

HHV8 is a new herpesvirus recently identified in the Kaposi's sarcoma lesions, and initially named Kaposi's sarcoma-associated herpesvirus. It is a member of gamma-2 herpesvirus family and it shows a number of homologies with the Epstein-Barr virus and the herpesvirus saimiri. HHV8 genome also codes for several proteins which are homologous to cellular proteins and could disturb the regulation mechanisms of cellular proliferation and apoptosis. This is the case for a viral IL6, an antiapoptotic factor homologous to Bcl2, a viral cyclin, a member of the IRF family (interferon regulatory factors) and a G-protein-coupled receptor homologous to the IL8 receptor. Seroprevalence studies showed that HHV8 infection was not ubiquitous but rather limited to some geographic areas (Italy, Greece, Africa), and to some populations of homosexual and bisexual individuals with sexually transmitted diseases. To date, several lines of epidemiologic evidence suggest that this virus is sexually transmitted, although other routes of transmission cannot be excluded.

[Erdheim-Chester disease. Clinico-pathologic study of two cases]. / Maladie d'Erdheim-Chester. Etude anatomo-clinique à propos de deux cas.

Erdheim-Chester disease is a rare visceral xanthogranulomatosis characterized by bilateral, symmetrical sclerosis of the metaphyseal regions of long bones and infiltration of foamy, lipid-laden histiocytes. Clinically, it ranges from an asymptomatic, focal process to a fatal, systemic disease. We report two new cases, different in their presentation and extension.

[Chester-Erdheim's disease. A case]. / Maladie de Chester-Erdheim. Une observation.

We report the 32nd case of a multivisceral form of Erdheim-Chester disease. This exceptional pathology is a diffuse xanthogranulomatosis which comes within the scope of histiocytosis. The originality of this case is due to cerebral localizations and to the fact that some symptoms have been observed for a long time: diabetes insipidus, exophthalmos and stubborn intertrigo.