BACKGROUND:The association between liver stiffness measurements (LSM) and mortality has not been fully described. In particular the effect of LSM on all-cause mortality taking sustained virological response (SVR) into account needs further study. METHODS:HIV/HCV participants in the French nation-wide, prospective, multicenter ANRS CO13 HEPAVIH cohort, with ≥1 LSM by FibroScan (FS) and a detectable HCV RNA when the first valid FS was performed were included. Cox proportional hazards models with delayed entry were performed to determine factors associated with all-cause mortality. LSM and SVR were considered as time dependent covariates. RESULTS:1,062 patients were included from 2005 to 2015 (69.8% men, median age 45.7 years (IQR 42.4-49.1)). 21.7% had baseline LSM >12.5 kPa. Median follow-up was 4.9 years (IQR 3.2-6.1). 727 (68.5%) were ever treated for HCV: 189 of them (26.0%) achieved SVR. 76 deaths were observed (26 liver-related, 10 HIV-related, 29 non-liver-non-HIV-related, 11 of unknown cause). At the age of 50, the mortality rate was 4.5% for patients with LSM ≤12.5 kPa and 10.8% for patients with LSM >12.5 kPa. LSM >12.5 kPa (adjusted Hazard Ratio [aHR] = 3.35 [2.06; 5.45], p<0.0001), history of HCV treatment (aHR = 0.53 [0.32; 0.90], p = 0.01) and smoking (past (aHR = 5.69 [1.56; 20.78]) and current (3.22 [0.93; 11.09]) versus never, p = 0.01) were associated with all-cause mortality independently of SVR, age, sex, alcohol use and metabolic disorders. CONCLUSION:Any LSM >12.5 kPa was strongly associated with all-cause mortality independently of SVR and other important covariates. Our results suggest that close follow-up of these patients should remain a priority even after achieving SVR.

Background: Hepatitis C virus (HCV) and HIV infections are associated with higher risk of autoimmune diseases and T-cell dysfunction. Setting: We evaluate prevalence and factors associated with the presence of autoimmune antinuclear (ANA), anti-smooth muscle actin (aSMA), and anti-liver kidney microsome (aLKM1) antibodies (Ab) in HCV/HIV-coinfected patients during the post-combined antiretroviral therapy era. Methods: A cross-sectional observational study nested in the ANRS CO13 HEPAVIH cohort (NCT number: NCT03324633). We selected patients with both ANA testing and T-cell immunophenotyping determination during the cohort follow-up and collected aLKM1 and aSMA data when available. Logistic regression models were built to determine factors associated with the presence of autoAb. Results: Two hundred twenty-three HCV/HIV-coinfected patients fulfilled selection criteria. Prevalence of ANA and aSMA was 43.5% and 23.2%, respectively, and both were detected in 13.3% of patients. Isolated aSMA were detected in 9.9% and aLKM1 in 2 patients. In multivariable analysis, only a low nadir CD4 T-cell count was significantly associated with ANA detection. Conclusions: ANA and aSMA detection remain frequent in HCV/HIV-coinfected patients during the post-combined antiretroviral therapy era, despite fair immune restoration. These results advocate for a close monitoring of ANA before immune checkpoint inhibitor therapy in these patients with greater caution for those with a low nadir CD4 T-cell count.

Objectives Although common among patients coinfected with HIV and hepatitis C virus (HCV), sleep disturbances (SD) are still poorly documented in this population in the HCV cure era. This longitudinal study aimed at analysing SD in HIV-HCV coinfected patients and identifying their clinical and sociobehavioural correlates. Methods We used 5-year annual follow-up data from 1047 participants in the French National Agency for Research on Aids and Viral Hepatitis Cohort 13 'Hepatite et VIH' (ANRS C013 HEPAVIH) cohort of HIV-HCV coinfected patients to identify clinical (medical records) and behavioural (self-administered questionnaires) correlates of SD (mixed-effects logistic regression). SD were identified using one item documenting the occurrence of insomnia or difficulty falling asleep (ANRS 'Action Coordonnee 24' self-reported symptoms checklist), and two items documenting perceived sleep quality (Center for Epidemiologic Studies Depression and WHO Quality of Life HIV-specific brief scales). Results Seven hundred and sixteen (68.4%) patients with completed self-administered questionnaires reported SD at their most recent follow-up visit. In the multivariable model, hazardous alcohol consumption (Alcohol Use Disorders Identification Test-Consumption score 4 for men, 3 for women) (adjusted odds ratio =1.61; 95% confidence interval: 1.09-2.36), depressive symptoms (6.78; 4.36-10.55) and the number of other physical and psychological self-reported symptoms (1.10; 1.07-1.13) were associated independently with SD after adjustment for sex, age and employment status. HCV cure was not associated significantly with SD. Conclusion SD remain frequent in HIV-HCV coinfected patients and are associated with a series of modifiable behavioural risk factors. independent of HCV cure, improved screening and comprehensive management of alcohol use, physical and psychological self-reported symptoms and depression are essential in this population. Closer investigation of these risk factors of SDs may both increase sleep quality and indirectly improve patients' clinical outcomes. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

Use of methiopropamine (MPA), a synthetic metamfetamine analog, has been detected since 2011 in Europe, but there is limited information on its acute toxicity. A 30-year-old man was admitted to the emergency department in a confused state, with paranoid delusion, auditory and visual hallucinatory experiences, and incoherent speech following the use of "synthacaine" (a slang term derived from "synthetic" and "cocaine"). Toxicological screening for pharmaceuticals and drugs of abuse by liquid chromatography-diode-array detector, gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS-MS) detected MPA, which was subsequently quantified by a specific LC-MS-MS method. Of note, 13 h after presentation to the emergency department, the plasma concentration of MPA was 14 ng/mL. This case report confirms the toxicity of MPA and the need for toxicological analysis to confirm the substance actually ingested by users of new psychoactive substances.

Objectives. - The authors had for objective to evaluate the management of a Plasmodium falciparum malaria in a Bordeaux teaching hospital EU.Methods. - One hundred and fifteen patients with falciparum malaria admitted between January 2004 and October 2006 were retrospectively studied and those with ambulatory treatment were questioned by phone.Results. - Fifty per cent of: patients had consulted a community physician prior to admission, and a parasitic test was made for 50% of these. In seven (27%) cases the test was wrong. Twenty-seven (87%) of ambulatory patients were contacted by phone. Eleven (41%) of these said they were not aware of the potential disease severity. Patients initially treated in ambulatory care and later hospitalized because of their evolution have either insisted to go back home or have been sent home because there was not enough room in the hospital. Hospitalization for at least 24 hours had been indicated for 83 patients (72%). Twelve patients (10%) have presented with symptoms of severe malaria. Atovaquone-proguanil was the main therapeutic regimen for inpatients and outpatients (n = 93, 81%). Twelve (10%) patients did not undergo follow-up parasitological assessment, 10 ambulatory patients (32%) and two hospitalized patients (2%).Conclusion. - An efficient hospital-community network and recent protocols are the best tools to rapidly refer patients to an adapted Structure with available trained staff and referent specialist. (C) 2009 Elsevier Masson SAS. All rights reserved.

Le nævus bleu unguéal est une prolifération mélanocytaire bénigne, rare de l’appareil unguéal. L’aspect clinique pose divers problèmes diagnostiques et nécessite une confrontation histologique afin d’éliminer un mélanome.Nous rapportons 2 cas de nævus bleu de la matrice unguéale d’aspect clinique différent ; l’un à type de tache matricielle pigmentée, l’autre prenant l’aspect d’une dépression longitudinale canaliforme associée à une macule matricielle pigmentée.L’analyse de ces deux observations et des cas de la littérature permet d’individualiser des formes cliniques et histologiques différentes.Nail unit blue nevus is a rare and benign melanocyte proliferation of the nail unit matrix.We report two cases of nail matrix blue nevi with a blue-black spot of the lunular area associated in the first case with a longitudinal nail groove.The analysis of our cases and of the previously reported cases give us the opportunity to describe different clinical and histological presentations.

American Journal of HematologyVolume 66, Issue 2 p. 153-154 Letters and CorrespondenceFree Access Mild hyperhomocysteinemia and penile venous thrombosis P. Mercié, P. Mercié Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorJ.F. Viallard, J.F. Viallard Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorI. Faure, I. Faure Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorB. Leng, B. Leng Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorJ.L. Pellegrin, J.L. Pellegrin Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorC. Vergnes, C. Vergnes Laboratoire d'Hématobiologie, Hôpital Haut-Lévêque, Centre Hospitalier, Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this author P. Mercié, P. Mercié Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorJ.F. Viallard, J.F. Viallard Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorI. Faure, I. Faure Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorB. Leng, B. Leng Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorJ.L. Pellegrin, J.L. Pellegrin Service de Médecine Interne, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this authorC. Vergnes, C. Vergnes Laboratoire d'Hématobiologie, Hôpital Haut-Lévêque, Centre Hospitalier, Universitaire de Bordeaux, 33604 Pessac, FranceSearch for more papers by this author First published: 21 February 2001 https://doi.org/10.1002/1096-8652(200102)66:2<153::AID-AJH1036>3.0.CO;2-LAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH, Vandenbroucke JP, Rosendaal FR. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 1996; 334: 759– 762. 2Hirsh J, Prins MH, Samama M. Approach to the thrombophilic patient. In: RW Colman, J Hirsh, VJ Marder, E Salzman, editors. Hemostasis and thrombosis: basic and clinical practice. Philadelphia: Lippincott; 1994. p 1543. 3Cable GG. Hyperhomocysteinaemia and upper extremity deep venous thrombosis: a case report. Aviat Space Environ Med 1999; 70: 701– 704. 4Lopez FF, Sweeney JD, Blair AJ, Sikov WM. Spontaneous venous thrombosis in a young patient with combined factor V Leiden and lupus anticoagulant. Am J Hematol 1999; 62: 58– 60. 5Wulf GM, Van Deerlin VM, Leonard DG, Bauer KA. Thrombosis in a patient with combined homozygosity for the factor V Leiden mutation and a mutation in the 3′-untranslated region of the prothrombin gene. Blood Coagul Fibrinolysis 1999; 10: 107– 110. Volume66, Issue2February 2001Pages 153-154 ReferencesRelatedInformation

The association between dermatomyositis and cancer is clearly established, but its frequency remains difficult to define.We report the case of an association between a dermatomyositis and a cancer of the piriform antrum. Four months after surgical treatment and radiotherapy, the increased macro-CK level gave us reason to suspect a cancer relapse with pulmonary, hepatic, splenic and renal metastases without progressive clinical signs.Mitochondrial macro-CK detection must evoke the presence of neoplasia with or without metastasis, which would be a poor prognosis, as has been shown in our patient.

INTRODUCTION:Primary non-Hodgkin's lymphoma of the nasal cavity is particular. Pathological characteristics mainly associate a prevalent NK lymphocyte phenotype, a frequent exposure to the Epstein-Barr virus and a poor sensitivity to radiotherapy compared to other lymph node localizations.EXEGESIS:The authors report the case of a 38-year-old man. The patient had previously presented a chronic maxillary sinusitis. After a diagnosis of Wegener's disease, the poor course under therapy resulted in a nasal lymphoma. Natural killer cell nasal lymphoma was confirmed with a leading biopsy at the same time as a serious clinical outcome. The patient died of septic shock with multivisceral failure.CONCLUSION:The two differential diagnoses of ulcerative lymphoma of the midface are ulcerative infectious diseases and Wegener's disease. We must not miss this severe disease, with its poor prognosis and variable, though sometimes rapid speed of evolution.

HIV-related lipodystrophy syndrome consists of an intriguing redistribution of body fat, often in association with glucidolipidic disorders [1–4]. The pathophysiological mechanism(s) for these events remains unclear, and a causal link to a specific drug or class of drugs is uncertain. Lipodystrophy syndrome is a frequent complication of HIV infection treatment with protease inhibitors (PI) [1,3,5,6]. Although inconclusive, recent reports have implied that several nucleoside reverse transcriptase inhibitors (NRTI) [7,8] or even the duration of viral suppression may be implicated in this syndrome. To the best of our knowledge, no data have been published on the lipodystrophy syndrome induced by a non-NRTI (NNRTI). We report six cases of lipodystrophy characterized by breast hypertrophy (BH) in HIV patients treated with highly active antiretroviral therapy (HAART) including an NNRTI such as efavirenz (Table 1).Table 1: HIV infection history, treatment and breast hypertrophy in six patients treated with efavirenz. Case 1 In 1996 HAART was started (stavudine, lamivudine and saquinavir) in a 43-year-old HIV-infected woman. From 1996 to 1999, the patient received several HAART regimens because of HIV load and CD4 cell count fluctuations, stavudine-related paraesthesia and abacavir-related skin allergy. A lipodystrophy syndrome appeared with lipoatrophy of the arms and legs and central fat accumulation, but without BH. Three weeks after modifying HAART by introducing efavirenz, the patient complained of a sensation of breast fullness associated with BH, and a very rapid two-size increase of brassiere size. The HIV-RNA load and CD4 cell count were approximately 376 copies/ml and 224/mm3(14.5%), respectively. Efavirenz was not stopped and her breast size stabilized. Case 2 Antiretroviral therapy in a 55-year-old HIV-infected women consisted of stavudine, lamivudine and nelfinavir. Several adverse effects were observed with PI (diarrhoea with nelfinavir, then nephritis with indinavir). The PI was replaced by nevirapine in 1998 and one month later hepatic cytolysis appeared (aspartate aminotransferase 142 lU/l and alanine aminotransferase 225 lU/l). The plasma HIV load remained at less than 50 copies/ml and the CD4 cell count was less than 70/mm3(5%). Triple therapy combinipg stavudine, lamivudine and efavirenz was begun. One month later, the patient described a marked increase in her breast size (more than two brassiere sizes). The treatment was continued, BH regressed slightly then stabilized 4 months after the start of efavirenz. Case 3 In a 51-year-old HIV-infected man, viral load was less than 50 copies/ml in 1998. The patient had facial lipoatrophy accompanied by slight lipodystrophy of the arms and legs. In 1999, the patient complained of digestive symptoms suspected to be induced by indinavir. PI was replaced by efavirenz. After 6 months of treatment, signs of lipodystrophy had stabilized and the digestive disorders had disappeared. The patient complained of pain in the right breast with an increase of volume. Hormone evaluation was normal. Antiretroviral therapy was maintained. Case 4 In a 43-year-old HIV-infected man, treatment was begun in 1996 by zidovudine then replaced by stavudine because of anaemia. The CD4 cell count was 286/mm3(13.6%) and HIV-RNA load was less than 500 copies/ml. In 1998, after several HAART regimens with PI, lipodystrophy syndrome appeared with severe fat wasting of the face and limbs. Indinavir was then replaced by efavirenz. Signs of lipoatrophy were stable for 2 months. During the third month, the patient experienced swelling of the external side of the right breast, non-painful, palpable, soft, unattached and suggestive of a developed breast or fat. The lesion was not readily visible but could be discerned with oblique lighting. The therapy was not modified. Case 5 In a 52-year-old HIV-infected man, several HAART regimens with PI were prescribed in 1996. During 1998, facial lipoatrophy and central fat accumulation, suspected to be induced by the antiretroviral triple therapy, appeared progressively. In early 1999, indinavir was replaced by efavirenz because the patient complained of lipodystrophy. In January 2000, several weeks after starting efavirenz, the patient noted pain associated with progressive hypertrophy of the right breast, which became readily visible within a few weeks. Case 6 In a 49-year-old HIV-infected man, first-line antiretroviral therapy with zidovudine accompanied by didanosine was started in 1995. In 1997, triple therapy was begun, lipodystrophy appeared in January 1999, with fat wasting of the arms, legs and face. In 1999, treatment was changed to efavirenz, ritonavir and amprenavir. Lipodystrophy remained stable. In May 2000, painful swelling of the right breast occurred suddenly and was associated with a modification of the lipodystrophy syndrome. Breast pain decreased spontaneously within a few weeks but BH persisted. The six HIV-infected patients (four men and two women) described had been treated with HAART including PI when different clinical signs of lipodystrophy appeared, but BH developed after the introduction of efavirenz. Biological data were normal and hormone evaluations showed no abnormality capable of explaining BH in men or in women. BH was always painful. BH occurred 1–6 months after starting efavirenz. Patient 2 described a partial regression of the BH. In all cases, treatment was continued and no other signs of lipodystrophy developed. Among the 330 patients followed in our unit, 258 received at least three antiretroviral agents, and 74 efavirenz-containing regimens, corresponding to 28.7% of the HIV-positive patients treated with HAART including efavirenz. Among the latter, 8.1% experienced breast enlargement. Delavirdine for patients 1 and 6, and nevirapine for patient 2, had been taken before efavirenz. Patient 2 suffered a hepatitis flare after taking nevirapine for 1 month. Patient 6 showed no signs of lipodystrophy after 18 months of therapy with delavirdine, but its responsibility for BH cannot be excluded as a drug family effect remains possible. BH is usually associated with the increased production of oestrogens or decreased levels of androgens [7]. Various known disorders and drugs may cause BH [7,9,10]. Isolated reports suggest that PI may promote BH in women [7,11–15] or in men [16–18]. The estimated prevalence of BH with PI ranges from 1 to 13% in the literature [19]. To the best of our knowledge, no case lipodystrophy has been described with NNRTI, particularly with efavirenz. Long-term follow-up of HIV-infected patients treated with HAART including NRTI, NNRTI and PI is needed. Patrick Merciéa Jean-François Viallarda Rodolphe Thiébautb Isabelle Faurea Patrick Rispala Bernard Lenga Jean-Luc Pellegrina

Introduction, - The association between dermatomyositis and cancer is clearly established, but its frequency remains difficult to define.Exegesis, - We report the case of an association between a dermatomyositis and a cancer of the piriform antrum. Four months after surgical treatment and radiotherapy, the increased macro-CK level gave us reason to suspect a cancer relapse with pulmonary, hepatic, splenic and renal metastases without progressive clinical signs.Conclusion. - Mitochondrial macro-CK detection must evoke the presence of neoplasia with or without metastasis, which would be a poor prognosis, as has been shown in our patient. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

Chronic hepatitis C virus (HCV) infection may be associated with numerous immune disorders, with vasculitis including polyarteritis nodosa, or with both. Cryoglobulinemia, which is often present, can also be expressed by vasculitis. We describe 2 cases of Churg-Strauss syndrome (CSS) in patients with HCV infection. We found no previous case of CSS accompanying HCV infection in the literature. The current patients were women aged 40 and 66 years. In both cases, a clinical and laboratory pattern suggesting CSS was found before the HCV infection was discovered. One patient had cryoglobulinemia. One patient was successfully treated with interferon (IFN). The other was treated for 18 months with IFN and corticosteroids. Second-line therapy consisting of IFN with ribavirin was successful. The emergence of HCV infection may have led to an induced form of CSS. The relationship among HCV, cryoglobulinemia, and CSS is not clear, but may be similar to that existing between polyarteritis nodosa and hepatitis B virus. These observations suggest that IFN-alpha therapy may be effective against CSS in HCV infected patients with or without cryoglobulinemia.

Introduction. - Pancreatic cancer is responsible for 6,000 deaths per year in France. During the course of the disease, venous thrombosis is common. Conversely, arterial thrombosis is rarely described.Exegesis. - We report the case of a 59-year-old patient with pancreatic adenocarcinoma. Treatment by gemcitabine allowed rapid and persistent improvement of the body weight and a prolonged survival (18 months). Sudden complication, i.e. splenic arterial thrombosis, reversed the favorable outcome.Conclusion. - Splenic venous thrombosis is a frequent complication occurring in the course of pancreatic cancer. It is easily diagnosed using abdominal computerized tomography. Arterial thrombosis is rarely observed. It might be due to either sporadic, unexpected, occurrence of cases related to the evolution of underlying pathological mechanisms, or to omitted treatment of vascular complications, as until the introduction of new anticancer drugs this disease was considered to be of very poor prognosis. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

Pancreatic cancer is responsible for 6,000 deaths per year in France. During the course of the disease, venous thrombosis is common. Conversely, arterial thrombosis is rarely described.We report the case of a 59-year-old patient with pancreatic adenocarcinoma. Treatment by gemcitabine allowed rapid and persistent improvement of the body weight and a prolonged survival (18 months). Sudden complication, i.e. splenic arterial thrombosis, reversed the favorable outcome.Splenic venous thrombosis is a frequent complication occurring in the course of pancreatic cancer. It is easily diagnosed using abdominal computerized tomography. Arterial thrombosis is rarely observed. It might be due to either sporadic, unexpected, occurrence of cases related to the evolution of underlying pathological mechanisms, or to omitted treatment of vascular complications, as until the introduction of new anticancer drugs this disease was considered to be of very poor prognosis.