Hepatitis E Virus seroprevalence and chronic infections in patients with HIV, Switzerland.

We screened 735 HIV-infected patients in Switzerland with unexplained alanine aminotransferase elevation for hepatitis E virus (HEV) immunoglobulin G. Although HEV seroprevalence in this population is low (2.6%), HEV RNA can persist in patients with low CD4 cell counts. Findings suggest chronic HEV infection should be considered as a cause of persistent alanine aminotransferase elevation.

Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia.

Acute myeloid leukemia arising from chronic myelomonocytic leukemia is currently classified as acute myeloid leukemia with myelodysplasia-related changes, a high-risk subtype. However, the specific features of these cases have not been well described. We studied 38 patients with chronic myelomonocytic leukemia who progressed to acute myeloid leukemia. We compared the clinicopathologic and genetic features of these cases with 180 patients with de novo acute myeloid leukemia and 34 patients with acute myeloid leukemia following myelodysplastic syndromes. We also examined features associated with progression from chronic myelomonocytic leukemia to acute myeloid leukemia by comparing the progressed chronic myelomonocytic leukemia cases with a cohort of chronic myelomonocytic leukemia cases that did not transform to acute myeloid leukemia. Higher white blood cell count, marrow cellularity, karyotype risk score, and Revised International Prognostic Scoring System score were associated with more rapid progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Patients with acute myeloid leukemia ex chronic myelomonocytic leukemia were older (P<0.01) and less likely to receive aggressive treatment (P=0.02) than de novo acute myeloid leukemia patients. Most cases showed monocytic differentiation and fell into the intermediate acute myeloid leukemia karyotype risk group; 55% had normal karyotype and 17% had NPM1 mutation. Median overall survival was 6 months, which was inferior to de novo acute myeloid leukemia (17 months, P=0.002) but similar to post myelodysplastic syndrome acute myeloid leukemia. On multivariate analysis of all acute myeloid leukemia patients, only age and karyotype were independent prognostic variables for overall survival. Our findings indicate that acute myeloid leukemia following chronic myelomonocytic leukemia displays aggressive behavior and support placement of these cases within the category of acute myeloid leukemia with myelodysplasia-related changes. The poor prognosis of these patients may be related to an older population and lack of favorable-prognosis karyotypes that characterize many de novo acute myeloid leukemia cases.

Surgery for incarcerated hernia: short-term outcome with or without mesh.

BACKGROUND: Incarcerated hernias represent about 5-15 % of all operated hernias. Tension-free mesh is the preferred technique for elective surgery due to low recurrence rates. There is however currently no consensus on the use of mesh for the treatment of incarcerated hernias, especially in case of bowel resection. AIM: The aims of this study were (i) to report our current practice for the treatment of incarcerated hernias, (ii) to identify risk factors for postoperative complications, and (iii) to assess the safety of mesh placement in potentially infected surgical fields. METHODS: This retrospective study included 166 consecutive patients who underwent emergency surgery for incarcerated hernia between January 2007 and January 2012 in two university hospitals. Demographics, surgical details, and short-term outcome were collected. Univariate analysis was employed to identify risk factors for overall, infectious, and major complications. RESULTS: Eighty-four patients (50.6 %) presented inguinal hernias, 43 femoral (25.9 %), 37 umbilical hernias (22.3 %), and 2 mixed hernias (1.2 %), respectively. Mesh was placed in 64 patients (38.5 %), including 5 patients with concomitant bowel resection. Overall morbidity occurred in 56 patients (32.7 %), and 8 patients (4.8 %) developed surgical site infections (SSI). Univariate risk factors for overall complications were ASA grade 3/4 (P = 0.03), diabetes (P = 0.05), cardiopathy (P = 0.001), aspirin use (P = 0.023), and bowel resection (P = 0.001) which was also the only identified risk factor for SSI (P = 0.03). In multivariate analysis, only bowel incarceration was associated with a higher rate of major morbidity (OR = 14.04; P = 0.01). CONCLUSION: Morbidity after surgery for incarcerated hernia remains high and depends on comorbidities and surgical presentation. The use of mesh could become current practice even in case of bowel resection.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the neuromodulation appropriateness consensus committee.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications. METHODS: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar. RESULTS: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated. CONCLUSIONS: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation.

Bosentan and/or Sildenafil for non-operable chronic thromboembolic pulmonary hypertension

Objectives: To evaluate outcome of patients treated "off-label" by bosentan and/or sildenafil for chronic thromboembolic pulmonary hypertension (CTEPH). Patients and methods: Since 2003, 18 patients (mean age 69 ± 11 years) have been treated with bosentan and/or sildenafil for CTEPH (mean pulmonary arterial resistance 8.1 ± 3.7 U Wood) in Lausanne University Hospital, with a follow-up of at least 12 months. Sixteen of them were inoperable because of distal disease and/or age or significant co-morbidities and 2 had persistent or recurrent pulmonary hypertension despite surgery. Efficacy of treatment was evaluated by comparison of New York Heart Association functional class (NYHA), six-minute walk test (6-MWT) and serum levels of N-terminal-pro brain natriuretic peptide (NT pro-BNP) at baseline (T0) and at 12 months (T12). Wilcoxon rank test was used for statistics. Results: At T0, median NYHA class was III (range II-IV), 6-MWT was 348 meters (5 and 95 centiles:0, 539) and NT pro-BNP was 387 mmol/l (58, 3508). At T12, 11 patients were treated with bosentan, 5 with sildenafil, 1 with inhaled Iloprost (because of failure of the two other treatments) and 1 with a combination of sildenafil and Iloprost. NYHA had improved in 10 patients, remained stable in 7 and worsened in 1 (median decrease 0.5 (-2; 0.2) p = 0.013). Six-MWT improved by a median of 15 meters (-142, +270) (p = 0.047) and NT pro-BNP decreased by a median of 65 mmol/l (-2988, +187) (p = n.s.). Among the 10 patients with a follow-up of 2 years or longer, two thirds remained stable and one third had worsened at 24 month. Treatments were well tolerated and only one patient had significant side effects (cutaneous reaction to bosentan) necessitating a switch to another treatment. Conclusion: In agreement with published data, bosentan and sildenafil improved functional status (NYHA, 6-MWT) and haemodynamics (NT pro BNP) in our patients with inoperable CTEPH. However these medications should not be used as substitute for surgery when the latter is applicable.

Hypothermie thérapeutique en traumatologie crânienne grave [Therapeutic hypothermia for severe traumatic brain injury].

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients.

Qualité de l'attachement dans la psychose et figures spirituelles

This study had mainly two goals: First of all, adult attachement was investigated in 28 patients with chronic psychosis and 18 controls, using the"Adult Attachment Interiew". This, as no previous research had ever done so with a scientific validated instrument. Diagnostic evaluations were performed with the SCID and symptomtic evaluation with the BPRS. Results showed that patients were more likely to have experienced traumatic experiences with their primary caregivers during their childhood then have controls. We were able to identify as well a high prevalence of insecure avoidant attachement in patients, which highlights the functional dimension of psychosis in the maintenance of the relation to primary attachement figures. This study shows that insecure avoidant attachement is related to an early outset as well as to an unfavourable prognosis. Second, quite a few researches on spirituality in psychosis have shown that patients were more likely to have spiritual believes or practices then indiviuals of a nonclinical population. Coping strategies related to spirituality and religion were identified as efficient for the majority. They can help dealing with all types of difficulties, specific symptoms and may enhance life quality (Mohr et al., 2006). Therefore we have investigated some of the underlying psychological processes in this type of coping strategies, using the conceptual framework of Bowlby's attachement theory. For most participants, both patients and controls, « spiritual figures » are functionning as attachement figures. Most of them are transposing the internal working model, achieved in relation to their primary caregivers, towards their "spiritual figure" even in case of an insecure attachement. - Cette recherche poursuit essentiellement deux objectifs. Premièrement, elle examine les modèles d'attachement à l'aide du « Adult Attachment Interview » chez 28 personnes souffrant de psychose chronique et chez 18 personnes ne souffrant d'aucune affection psychiatrique. En effet, aucune étude avant celle-ci n'avait investigué l'attachement chez des patients psychotiques chroniques à l'aide d'instruments scientifiquement validés. Les évaluations diagnostiques ont été réalisées à l'aide du SCID et les évaluations symptomatologiques à l'aide du BPRS. Dans ce contexte, nous avons pu montrer qu'une majorité de patients avaient été victimes d'expériences relationnelles traumatisantes en lien avec leurs premières figures d'attachement durant l'enfance. Nos résultats indiquent également l'importante prévalence d'un attachement insécure-détaché, qui reflète la dimension fonctionnelle des symptômes psychotiques visant la préservation du lien aux principales figures d'attachement. Ceux-ci montrent encore qu'un attachement insécure-détaché est associé à un début précoce de la maladie ainsi qu'à un pronostic défavorable. Deuxièmement, de nombreuses études ont montré que les patients psychotiques avaient davantage recours à des croyances et pratiques spirituelles/religieuses pour tenter de faire face à leurs difficultés que la population générale. Ce recours s'avère être efficace pour un grand nombre d'entre eux. Il leur permet souvent une meilleure gestion des difficultés, des symptômes et globalement améliore leur qualité de vie (Mohr et al., 2006). Nous avons donc examiné certaines des dimensions psychiques sousjacentes à ce type de stratégie de coping à l'aide de l'arrière-plan conceptuel de la théorie de l'attachement de Bowlby. Nous avons effectivement constaté qu'un grand nombre de participants, patients et contrôles, investissent des figures spirituelles sur le mode de l'attachement. Même en cas d'un attachement insécure, la majorité d'entre eux transposent leurs modèles internes opérants, acquis dans leur relation aux premières figures d'attachement, sur leur croyance en des figures spirituelles.

Genotype 3 is associated with accelerated fibrosis progression in chronic hepatitis C.

BACKGROUND/AIMS: While several risk factors for the histological progression of chronic hepatitis C have been identified, the contribution of HCV genotypes to liver fibrosis evolution remains controversial. The aim of this study was to assess independent predictors for fibrosis progression. METHODS: We identified 1189 patients from the Swiss Hepatitis C Cohort database with at least one biopsy prior to antiviral treatment and assessable date of infection. Stage-constant fibrosis progression rate was assessed using the ratio of fibrosis Metavir score to duration of infection. Stage-specific fibrosis progression rates were obtained using a Markov model. Risk factors were assessed by univariate and multivariate regression models. RESULTS: Independent risk factors for accelerated stage-constant fibrosis progression (>0.083 fibrosis units/year) included male sex (OR=1.60, [95% CI 1.21-2.12], P<0.001), age at infection (OR=1.08, [1.06-1.09], P<0.001), histological activity (OR=2.03, [1.54-2.68], P<0.001) and genotype 3 (OR=1.89, [1.37-2.61], P<0.001). Slower progression rates were observed in patients infected by blood transfusion (P=0.02) and invasive procedures or needle stick (P=0.03), compared to those infected by intravenous drug use. Maximum likelihood estimates (95% CI) of stage-specific progression rates (fibrosis units/year) for genotype 3 versus the other genotypes were: F0-->F1: 0.126 (0.106-0.145) versus 0.091 (0.083-0.100), F1-->F2: 0.099 (0.080-0.117) versus 0.065 (0.058-0.073), F2-->F3: 0.077 (0.058-0.096) versus 0.068 (0.057-0.080) and F3-->F4: 0.171 (0.106-0.236) versus 0.112 (0.083-0.142, overall P<0.001). CONCLUSIONS: This study shows a significant association of genotype 3 with accelerated fibrosis using both stage-constant and stage-specific estimates of fibrosis progression rates. This observation may have important consequences for the management of patients infected with this genotype.

Rethinking the triggering inflammatory processes of chronic periaortitis.

Chronic periaortitis (CP) is an uncommon inflammatory disease which primarily involves the infrarenal portion of the abdominal aorta. However, CP should be regarded as a generalized disease with three different pathophysiological entities, namely idiopathic retroperitoneal fibrosis (RPF), inflammatory abdominal aortic aneurysm and perianeurysmal RPF. These entities share similar histopathological characteristics and finally will lead to fibrosis of the retroperitoneal space. Beside fibrosis, an infiltrate with variable chronic inflammatory cell is present. The majority of these cells are lymphocytes and macrophages as well as vascular endothelial cells, most of which are HLA-DR-positive. B and T cells are present with a majority of T cells of the T-helper phenotype. Cytokine gene expression analysis shows the presence of interleukin (IL)-1alpha, IL-2, IL-4, interferon-gamma and IL-2 receptors. Adhesion molecules such as E-selectin, intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were also found in aortic tissue, and may play a significant role in CP pathophysiology. Although CP pathogenesis remains unknown, an exaggerated inflammatory response to advanced atherosclerosis (ATS) has been postulated to be the main process. Autoimmunity has also been proposed as a contributing factor based on immunohistochemical studies. The suspected allergen may be a component of ceroid, which is elaborated within the atheroma. We review the pathogenesis and the pathophysiology of CP, and its potential links with ATS. Clinically relevant issues are summarized in each section with regard to the current working hypothesis of this complex inflammatory disease.

Hemodynamic consequences of chronic parasympathetic blockade with a peripheral muscarinic antagonist

Résumé Alors que le système nerveux sympathique a un rôle bien établi dans la régulation de la pression artérielle, l'influence de la fonction ou dysfonction du système parasympathique sur la pression artérielle n'est pas évidente, en particulier à long terme. Nous avons testé l'hypothèse que l'inhibition chronique du système parasympathique a un effet persistant sur la pression artérielle (PA), la fréquence cardiaque (FC) et la variabilité de la pression artérielle (VPA). Des rats de type Sprague Dawley ont été instrumentés pour monitoring de la pression artérielle 22h par jour par télémétrie et abrités dans des cages métaboliques. Après guérison de l'intervention et après une période contrôle de référence, de la scopolamine methyl bromide (SMB), un antagoniste muscarinique périphérique, a été perfusé i.v. pendant 12 jours. Le tout fut suivi d'une période de récupération de 10 jours. La SMB a entraîné une augmentation rapide de la PA de 98±2 mmHg à un maximum de 108±2 mmHg le deuxième jour de perfusion de la SMB puis la PA s'est stabilisée à une valeur plateau de +3±1 mmHg au dessus de la valeur contrôle (P < 0.05). Après l'arrêt de la perfusion de SMB, la PA moyenne a diminué de 6±1 mmHg. La FC a augmenté immédiatement et est restée significativement au dessus de la valeur contrôle le dernier jour de 1a perfusion de SMB. La SMB a également induit une diminution de la variabilité à court terme de la FC (au sein d'intervalles de 30 minutes et une augmentation de la variabilité à court terme et à long terme (entre intervalles de 30 minutes) de la PA. Ces données suggèrent que l'inhibition muscarinique périphérique chronique conduit à une augmentation modeste mais persistante de la PA, FC et VPA, qui sont des facteurs de risque cardiovasculaires connus.

Comparisons of serum vitamin d levels, status, and determinants in populations with and without chronic kidney disease not requiring renal dialysis: a 24-hour urine collection population-based study.

OBJECTIVE: Vitamin D deficiency is frequent in the general population and might be even more prevalent among populations with kidney failure. We compared serum vitamin D levels, vitamin D insufficiency/deficiency status, and vitamin D level determinants in populations without chronic kidney disease (CKD) and with CKD not requiring renal dialysis. DESIGN AND METHODS: This was a cross-sectional, multicenter, population-based study conducted from 2010 to 2011. Participants were from 10 centers that represent the geographical and cultural diversity of the Swiss adult population (≥15 years old). INTERVENTION: CKD was defined using estimated glomerular filtration rate and 24-hour albuminuria. Serum vitamin D was measured by liquid chromatography-tandem mass spectrometry. Statistical procedures adapted for survey data were used. MAIN OUTCOME MEASURE: We compared 25-hydroxy-vitamin D (25(OH)D) levels and the prevalence of vitamin D insufficiency/deficiency (serum 25(OH)D < 30 ng/mL) in participants with and without CKD. We tested the interaction of CKD status with 6 a priori defined attributes (age, sex, body mass index, walking activity, serum albumin-corrected calcium, and altitude) on serum vitamin D level or insufficiency/deficiency status taking into account potential confounders. RESULTS: Overall, 11.8% (135 of 1,145) participants had CKD. The 25(OH)D adjusted means (95% confidence interval [CI]) were 23.1 (22.6-23.7) and 23.5 (21.7-25.3) ng/mL in participants without and with CKD, respectively (P = .70). Vitamin D insufficiency or deficiency was frequent among participants without and with CKD (75.3% [95% CI 69.3-81.5] and 69.1 [95% CI 53.9-86.1], P = .054). CKD status did not interact with major determinants of vitamin D, including age, sex, BMI, walking minutes, serum albumin-corrected calcium, or altitude for its effect on vitamin D status or levels. CONCLUSION: Vitamin D concentration and insufficiency/deficiency status are similar in people with or without CKD not requiring renal dialysis.

IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C.

Background & Aims: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-alpha/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.Methods: IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naive Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-alpha 2a (180 mu g weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.Results: In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89 IU/ml among T carriers vs. 2.06 among others, adjusted p <0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p <0.001). In univariate analyses, Trs12979860 was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, Trs12979860 was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline.Conclusions: Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-alpha/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

From controlling to letting go : what are the psychosocial needs of parents of adolescents with a chronic illness?

While one of the main objectives of adolescence is to achieve autonomy, for the specific population of adolescents with a chronic illness (CI), the struggle for autonomy is accentuated by the limits implied by their illness. However, little is known concerning the way their parents manage and cope with their children's autonomy acquisition. Our aim was to identify the needs and preoccupations of parents of adolescents with CI in coping with their children's autonomy acquisition and to determine whether mothers and fathers coped differently. Using a qualitative approach, 30 parents of adolescents with CI participated in five focus groups. Recruitment took place in five specialized pediatric clinics from our university hospital. Thematic analysis was conducted. Transcript analyses suggested four major categories of preoccupations, those regarding autonomy acquisition, giving or taking on autonomy, shared management of treatment and child's future. Some aspects implied differences between mothers' and fathers' viewpoints and ways of experiencing this period of life. Letting go can be hard for the father, mother, adolescent or all three. Helping one or the other can in turn improve family functioning as a whole. Reported findings may help health professionals better assist parents in managing their child's acquisition of autonomy.

Genetic loci influencing kidney function and chronic kidney disease.

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.6 x 10(-4), respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.