Percutaneous drainage versus emergency cholecystectomy for the treatment of acute cholecystitis in critically ill patients: does it matter?

Background The aim if this study was to compare percutaneous drainage (PD) of the gallbladder to emergency cholecystectomy (EC) in a well-defined patient group with sepsis related to acute calculous/acalculous cholecystitis (ACC/AAC).Methods Between 2001 and 2007, all consecutive patients of our ICU treated by either PD or EC were retrospectively analyzed. Cases were collected from a prospective database. Percutaneous drainage was performed by a transhepatic route and EC by open or laparoscopic approach. Patients' general condition and organ dysfunction were assessed by two validated scoring systems (SAPS II and SOFA, respectively). Morbidity, mortality, and long-term outcome were systematically reviewed and analyzed in both groups.Results Forty-two patients [median age = 65.5 years (range = 32-94)] were included; 45% underwent EC (ten laparoscopic, nine open) and 55% PD (n = 23). Both patient groups had similar preoperative characteristics. Percutaneous drainage and EC were successful in 91 and 100% of patients, respectively. Organ dysfunctions were similarly improved by the third postoperative/postdrainage days. Despite undergoing PD, two patients required EC due to gangrenous cholecystitis. The conversion rate after laparoscopy was 20%. Overall morbidity was 8.7% after PD and 47% after EC (P = 0.011). Major morbidity was 0% after PD and 21% after EC (P = 0.034). The mortality rate was not different (13% after PD and 16% after EC, P = 1.0) and the deaths were all related to the patients' preexisting disease. Hospital and ICU stays were not different. Recurrent symptoms (17%) occurred only after ACC in the PD group.Conclusions In high-risk patients, PD and EC are both efficient in the resolution of acute cholecystitis sepsis. However, EC is associated with a higher procedure-related morbidity and the laparoscopic approach is not always possible. Percutaneous drainage represents a valuable intervention, but secondary cholecystectomy is mandatory in cases of acute calculous cholecystitis.

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download

Thérapie focale du cancer de la prostate: rationnel, résultats et perspectives [Focal therapy in prostate cancer: rationale, results and perspectives].

Focal therapy is a novel treatment strategy in prostate cancer aiming to treat only the area of the gland harbouring clinically significant disease. The overall objective is to maintain the oncological benefit of active treatment while minimising treatment-related morbidity. Leading centres are currently evaluating various minimally invasive technologies in a rigorous manner. Oncological and functional results in mid-term are encouraging with low rate of urinary incontinence and erectile dysfunction. However, the oncological outcome needs to be evaluated in the long-term in the light of the prolonged natural history of the disease.

Extraintestinal manifestations of Crohn's disease.

In each case of extraintestinal manifestations of Crohn's disease, active disease, if present, should be treated to induce remission, which may positively influence the course of most concomitant extraintestinal manifestations. For some extraintestinal manifestations, however, a specific treatment should be introduced. This latter part of disease management will be discussed in this chapter, in particular for pyoderma gangrenosum, uveitis, spondylarthropathy--axial arthropathy--and primarysclerosing cholangitis, which have also been described in quiescent Crohn's disease. Few new drugs for the treatment of extraintestinal manifestations of Crohn's disease have been developed in the past and only the role of infliximab has increased in Crohn's disease-related extraintestinal manifestations. Drugs specifically aimed at this treatment, stemming from a few randomized controlled studies or case series, are sulfasalazine, 5-ASA, corticosteroids, azathioprine or 6-mercaptopurine, methotrexate, infliximab, dapsone and cyclosporine or tacrolimus.

The difference of disease perception by juvenile idiopathic arthritis patients and their parents : analysis of the JAMAR questionnaire.

BACKGROUND: The JAMAR (Juvenile Arthritis Multidimensional Assessment Report) has been developed to evaluate the perception of the patient and his parents on different items: well-being, pain, functional status, quality of life, disease activity, disease course, side effects of medication, therapeutic compliance and satisfaction with illness outcome. Our aim was to compare disease's perception by JIA patients and their parents. METHODS: We included into the study 100 consecutive patients over 7 years of age. We asked both parent and child to complete the JAMAR questionnaire. For each patient we recorded demographic and disease related data. We examined the level of disagreement between children and parents for the quantitative items of the JAMAR: VAS Pain, VAS Disease Activity, VAS Well Being, Juvenile Arthritis Functional Score, HRQoL. Then we looked for a relation between discordance-rate and demographic and clinical variables. RESULTS: Children and parents' median scores for all five items were similar. Individual dyads agreement was low, with a large amount of pairs (80) discordant for at least one item. We found higher MD VAS and JADAS in more discordant dyads, suggesting that when the disease is more active discordance between child and parent increase. CONCLUSION: The JAMAR questionnaire is an important tool that helps clinicians to detect divergent child and parent's disease perceptions. It is essential that both patients and parents fill the JAMAR questionnaire for a complete clinical and psychosocial evaluation.

Health Related Quality of Life after Childhood Cancer - A Finnish Nationwide survey

The purpose of this Finnish epidemiological nationwide cross-sectional study was to evaluate the Health Related Quality of Life (HRQL) of young people that have survived childhood cancer at least four years after cancer diagnosis. The study aims were (1) to increase knowledge and understanding about the relationship between childhood cancer and its treatment and HRQL of childhood cancer survivors and (2) to identify survivors who need and could benefit from ongoing long-term follow-up, as well as (3) to identify what kind of aftercare the childhood cancer survivors will possibly need. HRQL and fatigue of currently still young survivors of extracranial childhood malignancies were evaluated with self-reports and parent proxy reports. HRQL was measured with age-appropriate generic instruments: PedsQL™, SF-36, 15D, 16D and 17D. Fatigue for children and adolescents aged below 18 years was measured with the PedsQL™ Multidimensional Fatigue Scale Finnish version. PedsQL™ parent-proxy and the PedsQL™ Multidimensional Fatigue Scale Parentproxy instruments were used to assess the perception of the parents on HRQL and fatigue of their children and adolescents. Postal-survey questionnaires were mailed to 852 childhood cancer survivors aged 11-27 years and their randomly selected gender-, age and living-place matched controls, as well as under 18-year-old children´s parents. A total of 474 survivors, 595 controls, 209 survivor’s parent and 253 control’s parent replied. The mean age of survivors at the time of the study was 18.4 years. The mean length of survival was 12.3 years, and the mean age at diagnosis 5.5 years. The most of the Finnish childhood cancer survivors evaluated that their HRQL as good. Survivors rated their HRQL equal or higher than their controls. The only dimension where the survivors scored poorer than the controls was the 15D mobility dimension. Survivors of childhood cancer did not suffer from significant fatigue. There were subgroups of childhood cancer survivors who had poorer level of HRQL, and suffered from fatigue more than the reference group. The demographic factors that associated with poorer HRQL were female gender, greater weight, living alone, need of remedial education, an additional non-cancer diagnosis, survivors with siblings, and self-reported unhappiness. Disease-related factors that associated with poorer HRQL were higher age at the time of diagnosis, the diagnosis of Wilms tumor, neuroblastoma, or osteosarcoma, and treatment with stem cell transplantation. The factors associated with more fatigue in survivors were male gender, older age at evaluation, the need of remedial education at school, lower overall average grade in the latest school marks report, length of survival more than 10 years, lower HRQL-scores, and a sarcoma diagnosis. However, all the used demographic and disease related factors explained only about one third of the variation in the HRQL scores. In open questions, the survivors were most worried about their physical health, but were also worried about their mental health, cancer inheritance, late-effects, and fertility and relapse issues. It seems that there are subgroups of survivors who need and could benefit from ongoing long-term follow-up. In the future, the survivors of childhood cancer need more information about their physical and mental health, as well as on their cancer inheritance, possible late-effects including fertility issues, and on the risk of relapse.

Circulating levels of inflammation-associated miR-155 and endothelial-enriched miR-126 in patients with end-stage renal disease

Circulating microRNAs (miRNAs) may represent a potential noninvasive molecular biomarker for various pathological conditions. Moreover, the detection of circulating miRNAs can provide important novel disease-related information. In particular, inflammation-associated miR-155 and endothelial-enriched miR-126 are reported to be associated with vascular homeostasis. Vascular damage is a common event described in end-stage renal disease (ESRD). We hypothesized that miR-155 and miR-126 may be detectable in the circulation and serve as potential biomarkers for risk stratification. In this study, we assessed miR-155 and miR-126 in the plasma of 30 ESRD patients and 20 healthy controls using real-time quantification RT-PCR. The circulating levels of miR-155 and miR-126 were significantly reduced in patients with ESRD compared to healthy controls. However, there was no significant difference of circulating miR-155 and miR-126 levels between prehemodialysis and posthemodialysis patients. Furthermore, both circulating miR-126 and miR-155 correlated positively with estimated glomerular filtration rate (miR-126: r = 0.383, P = 0.037; miR-155: r = 0.494, P = 0.006) and hemoglobin (miR-126: r = 0.515, P = 0.004; miR-155: r = 0.598, P < 0.001) and correlated inversely with phosphate level (miR-126: r = -0.675, P < 0.001; miR-155: r = -0.399, P = 0.029). Pearson’s correlation was used to compare circulating levels of miRNAs with clinical parameters. These results suggested that circulating miR-155 and miR-126 might be involved in the development of ESRD. Further studies are needed to demonstrate the role of circulating miR-155 and miR-126 as candidate biomarkers for risk estimation.

Accounting for the economic risk, caused by variation in disease severity, in fungicide dose decisions: exemplified for Mycosphaerella graminicola on winter wheat

A method is presented to calculate economic optimum fungicide doses accounting for the risk-aversion of growers responding to variability in disease severity between crops. Simple dose-response and disease-yield loss functions are used to estimate net disease-related costs (fungicide cost, plus disease-induced yield loss) as a function of dose and untreated severity. With fairly general assumptions about the shapes of the probability distribution of disease severity and the other functions involved, we show that a choice of fungicide dose which minimises net costs on average across seasons results in occasional large net costs caused by inadequate control in high disease seasons. This may be unacceptable to a grower with limited capital. A risk-averse grower can choose to reduce the size and frequency of such losses by applying a higher dose as insurance. For example, a grower may decide to accept ‘high loss’ years one year in ten or one year in twenty (i.e. specifying a proportion of years in which disease severity and net costs will be above a specified level). Our analysis shows that taking into account disease severity variation and risk-aversion will usually increase the dose applied by an economically rational grower. The analysis is illustrated with data on septoria tritici leaf blotch of wheat caused by Mycosphaerella graminicola. Observations from untreated field plots at sites across England over three years were used to estimate the probability distribution of disease severities at mid-grain filling. In the absence of a fully reliable disease forecasting scheme, reducing the frequency of ‘high loss’ years requires substantially higher doses to be applied to all crops. Disease resistant cultivars reduce both the optimal dose at all levels of risk and the disease-related costs at all doses.

Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

AIM: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study. METHODS: Interactions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test. RESULTS: After Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (-4.0%, P=6.26e-24) compared to those with either one or no major alleles (-2.3%, P≤8.201e-07, for both) of the VDR SNP rs2239179. CONCLUSION: We found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.

Consumo de álcool e risco para doença coronariana na região metropolitana de São Paulo: uma análise do Projeto GENACIS

OBJETIVOS: Examinar a associação entre consumo de álcool e risco para doença coronariana em amostra populacional. MÉTODOS: Estudo transversal, de base populacional, conduzido de janeiro/2006 a junho/2007, na região metropolitana de São Paulo, como parte do estudo internacional (Gender, Alcohol, and Culture: an International Study). Os sujeitos (1.501, sendo 609 homens e 892 mulheres) eram residentes da região metropolitana de São Paulo, tinham 30 anos ou mais de idade e foram selecionados aleatoriamente, a partir de amostragem complexa por conglomerados. Todos os indivíduos consentiram em participar da pesquisa. A variável dependente foi risco cardíaco avaliado através do WHO Rose Angina Questionnaire. A análise multivariada consistiu em regressão logística, tendo sido realizado ajuste para uso de tabaco e índice de massa corpórea. RESULTADOS: A taxa de resposta foi 75%. Ser mulher, ter mais idade, ser negro, fumante e ter um índice de massa corpórea elevado, foram associados a maior risco para doença coronariana. Indivíduos que nunca beberam na vida (OR = 2,22) e ex-bebedores (OR = 2,42) tiveram maior risco de doença cardíaca do que aqueles que informaram beber até 19 g de álcool por dia, sem episódios de beber excessivo. Entre os que tiveram episódios de embriaguês observou-se uma tendência a maior risco (OR = 3,95, p = 0,09). CONCLUSÕES: Nossos achados sugerem um menor risco para doença coronariana entre os bebedores moderados. Destaca-se que os estudos que avaliam o impacto do álcool sobre doença cardíaca precisam identificar o padrão de uso de álcool dos sujeitos, visto que este aspecto pode modificar o risco. Políticas públicas são necessárias para reduzir o uso nocivo de álcool e a morbidade a ele relacionada no país.

La gripe en adultos en américa latina, situación actual y tendencias futuras: Una declaración de consenso

In Latin America, adult influenza is a serious disease that exacts a heavy burden in terms of morbidity, mortality, and cost. Although much has been written about the disease itself, relatively little information has been compiled on what could be done to reduce its impact across the region, particularly from the perspective of clinicians with firsthand experience in confronting its effects. To fill this data gap, in 2011, the Pan American Health and Education Foundation (PAHEF) and the U.S.-based nonprofit Fighting Infectious Diseases in Emerging Countries (FIDEC) organized a conference and convened a panel of Latin American scientistclinicians with experience and expertise in adult influenza in the region to 1) discuss the major issues related to the disease and 2) develop and produce a consensus statement summarizing its impact as well as current efforts to diagnose, prevent, and treat it. The consensus panel concluded a more concerted and better-coordinated effort was needed to reduce the adverse impact of seasonal influenza and future pandemics, including more surveillance, more active involvement by both governmental and nongovernmental organizations, and a much greater effort to vaccinate more adults, especially those at high risk of contracting the disease. In addition, a new approach for diagnosing influenza was recommended.

Indocyanine green angiography findings in patients with long-standing Vogt-Koyanagi-Harada disease: a cross-sectional study

Background: To investigate indocyanine green angiography (ICGA) findings in patients with long-standing Vogt-Koyanagi-Harada (VKH) disease and their correlation with disease activity on clinical examination as well as with systemic corticosteroid therapy. Methods: Twenty-eight patients (51 eyes) with long-standing (>= 6 months from disease onset) VKH disease whose treatment was tapered based only in clinical features were prospectively included at a single center in Brazil. All patients underwent standardized clinical evaluation, which included fundus photography, fluorescein angiography and ICGA. Clinical disease activity was determined based in the Standardization in Uveitis Nomenclature Working Group. Fisher exact test and logistic regression models were used for statistical analysis. Results: Disease-related choroidal inflammation on ICGA was observed in 72.5% (31 of 51 eyes). Angiographic findings suggestive of (choroidal and/or retinal) disease activity were not observed on FA. Clinically active disease based on clinical evaluation was observed in 41.2% (21 of 51 eyes). In these 21 eyes, disease-related choroidal inflammation on ICGA was observed in 76.2% (16 of 21 eyes); in the remaining eyes (without clinical active disease) disease-related choroidal inflammation on ICGA was observed in 70.0% (21 of 30 eyes). In respect to systemic corticosteroid therapy, 10 patients (18 of 51 eyes) were under treatment with prednisone. In these 10 (18 of 51 eyes) patients, disease-related choroidal inflammation on ICGA was observed in 83.3% (15 of 18 eyes); in the remaining patients (33 of 51 eyes) disease-related choroidal inflammation on ICGA was observed in 66.7% (22 of 33 eyes). Conclusion: ICGA findings suggestive of disease-related choroidal inflammation were observed in a considerable proportion of patients with long-standing VKH disease, independent of the inflammatory status of the disease on clinical examination or current use of systemic corticosteroid. Therefore, the current study reinforces the crucial role of ICGA to assist the management and treatment of patients with long-standing VKH disease.

Vasculitides associated with IgG antineutrophil cytoplasmic autoantibodies in childhood

Immunoglobulin (Ig)G antineutrophil cytoplasmic autoantibodies are causally associated with necrotizing vasculitides that are characterized immunopathologically by little or no deposition of immunoreactants, such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss angiitis, "renal-limited" vasculitis and a number of drug-induced vasculitides. Clinical routine testing targets the antigens myeloperoxidase and proteinase 3. However, in all of the conditions mentioned, the renal histopathologic findings are indistinguishable. Churg-Strauss angiitis (characterized by necrotizing vasculitis, granulomatous inflammation and tissue eosinophilia), Wegener granulomatosis (characterized by necrotizing vasculitis and granulomatous inflammation) and microscopic polyangiitis (characterized by necrotizing vasculitis) often present with fever, weight loss and a multisystem involvement (ear, nose, throat, lung, eyes, peripheral nerve and heart). Fifty years ago these conditions were very often fatal within 6 months of diagnosis. The introduction of corticosteroids and cyclophosphamide has resulted in a dramatic clinical benefit. Patients who develop treatment-related morbidity can be switched from cyclophosphamide to azathioprine after achieving remission. In patients with less severe disease, methotrexate achieves remission with a success rate similar to that of cyclophosphamide. Plasma exchange, in association with immunosuppression, is likely to be a beneficial therapy for patients with severe kidney disease or pulmonary hemorrhage.

Progressive dopamine and hypocretin deficiencies in Parkinson's disease: is there an impact on sleep and wakefulness?

Sleep-wake disturbances are frequent in patients with Parkinson's disease, but prospective controlled electrophysiological studies of sleep in those patients are surprisingly sparse, and the pathophysiology of sleep-wake disturbances in Parkinson's disease remains largely elusive. In particular, the impact of impaired dopaminergic and hypocretin (orexin) signalling on sleep and wakefulness in Parkinson's disease is still unknown. We performed a prospective, controlled electrophysiological study in patients with early and advanced Parkinson's disease, e.g. in subjects with presumably different levels of dopamine and hypocretin cell loss. We compared sleep laboratory tests and cerebrospinal fluid levels with hypocretin-deficient patients with narcolepsy with cataplexy, and with matched controls. Nocturnal sleep efficiency was most decreased in advanced Parkinson patients, and still lower in early Parkinson patients than in narcolepsy subjects. Excessive daytime sleepiness was most severe in narcolepsy patients. In Parkinson patients, objective sleepiness correlated with decrease of cerebrospinal fluid hypocretin levels, and repeated hypocretin measurements in two Parkinson patients revealed a decrease of levels over years. This suggests that dopamine and hypocretin deficiency differentially affect sleep and wakefulness in Parkinson's disease. Poorer sleep quality is linked to dopamine deficiency and other disease-related factors. Despite hypocretin cell loss in Parkinson's disease being only partial, disturbed hypocretin signalling is likely to contribute to excessive daytime sleepiness in Parkinson patients.

Life cycle complexity, environmental change and the emerging status of salmonid proliferative kidney disease

P>1. Proliferative kidney disease (PKD) is a disease of salmonid fish caused by the endoparasitic myxozoan, Tetracapsuloides bryosalmonae, which uses freshwater bryozoans as primary hosts. Clinical PKD is characterised by a temperature-dependent proliferative and inflammatory response to parasite stages in the kidney.;2. Evidence that PKD is an emerging disease includes outbreaks in new regions, declines in Swiss brown trout populations and the adoption of expensive practices by fish farms to reduce heavy losses. Disease-related mortality in wild fish populations is almost certainly underestimated because of e.g. oversight, scavenging by wild animals, misdiagnosis and fish stocking.;3. PKD prevalences are spatially and temporally variable, range from 0 to 90-100% and are typically highest in juvenile fish.;4. Laboratory and field studies demonstrate that (i) increasing temperatures enhance disease prevalence, severity and distribution and PKD-related mortality; (ii) eutrophication may promote outbreaks. Both bryozoans and T. bryosalmonae stages in bryozoans undergo temperature- and nutrient-driven proliferation.;5. Tetracapsuloides bryosalmonae is likely to achieve persistent infection of highly clonal bryozoan hosts through vertical transmission, low virulence and host condition-dependent cycling between covert and overt infections. Exploitation of fish hosts entails massive proliferation and spore production by stages that escape the immune response. Many aspects of the parasite's life cycle remain obscure. If infectious stages are produced in all hosts then the complex life cycle includes multiple transmission routes.;6. Patterns of disease outbreaks suggest that background, subclinical infections exist under normal environmental conditions. When conditions change, outbreaks may then occur in regions where infection was hitherto unsuspected.;7. Environmental change is likely to cause PKD outbreaks in more northerly regions as warmer temperatures promote disease development, enhance bryozoan biomass and increase spore production, but may also reduce the geographical range of this unique multihost-parasite system. Coevolutionary dynamics resulting from host-parasite interactions that maximise fitness in previous environments may pose problems for sustainability, particularly in view of extensive declines in salmonid populations and degradation of many freshwater habitats.