Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Content validation of the dimensions constituting non-adherence to treatment of arterial hypertension

The objective of the study was to validate the content of the dimensions that constituted nonadherence to treatment of arterial systemic hypertension. It was a methodological study of content validation. Initially an integrative review was conducted that demonstrated four dimensions of nonadherence: person, disease/treatment, health service, and environment. Definitions of these dimensions were evaluated by 17 professionals, who were specialists in the area, including: nurses, pharmacists and physicians. The Content Validity Index was calculated for each dimension (IVCi) and the set of the dimensions (IVCt), and the binomial test was conducted. The results permitted the validation of the dimensions with an IVCt of 0.88, demonstrating reasonable systematic comprehension of the phenomena of nonadherence.

Laboratory-based versus non-laboratory-based CVD risk analysis.

Commentaire de: Gaziano TA, Young CR, Fitzmaurice G, Atwood S, Gaziano JM. Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort. Lancet. 2008;371(9616):923-31. PMID: 18342687

Factors associated with beliefs about adherence to non-pharmacological treatment of patients with heart failure

This study aimed at assessing beliefs about the benefits and barriers to adherence to daily self-monitoring of weight/edema in patients with heart failure, and the influence of demographic and clinical variables on those beliefs. 105 patients were interviewed. The mean of the subscales Benefits and Barriers were 20.2 (± 5.7) and 30.1 (±7.1), respectively. Patients perceived that adherence to daily self-monitoring of weight/edema could keep them healthy, improve their quality of life and decrease the chances of readmission. Approximately half of patients (46.7%) reported forgetting this measure. Those who controlled weight once a month were more likely to have barriers to adherence (OR= 6.6; IC 95% 1.9-13.8; p=0.01), showing this measure to be the main factor related to perceived barriers. Education in health can contribute with the development of strategies aimed at lowering barriers and increasing benefits of this control.

Ankle-Brachial Index: Nurses Strategy To Cardiovascular Disease Risk Factors Identification

Elevated risk of fatal and non-fatal cardiovascular events is associated with high prevalence of peripheral arterial disease, with assessment through the ankle-brachial index (ABI). This study aimed to demonstrate that the ABI and the Edinburgh Claudication Questionnaire are tools to be used by nurses in prevention and/or treatment of CVD (cardiovascular disease). A cross-sectional study was carried out with patients from a cardiovascular clinic. The Edinburgh Claudication Questionnaire was applied and the ABI was measured with the formula (ABI= Blood Pressure Ankle/Blood Pressure Brachial). A total of 115 patients were included, most were females (57.4%), aged 60.6 ± 12.5 years. The most prevalent risk factors were hypertension (64.3%), physical inactivity (48.7%) and family history (58.3%). The study showed that abnormal ABI was frequently found and 42.6% of the patients with abnormal ABI showed intermittent claudication. The method to evaluate the ABI associated to the Edinburg Claudication Questionnaire, can be easily used by nurses in the clinical evaluation of asymptomatic and symptomatic CVD patients.

Video-assisted right supradiaphragmatic thoracic duct ligation for non-traumatic recurrent chylothorax

BACKGROUND: Chylothorax is an uncommon disorder with respiratory, nutritional and immunological manifestations. Surgical management is indicated in case of recurrence or failure after conservative treatment. We report our experience with video-assisted right-sided supradiaphragmatic thoracic duct ligation for non-traumatic, non-postoperative persistent or recurrent chylothorax. PATIENTS AND METHODS: The medical records of six patients operated at our institution between 1999 and 2004 were retrospectively reviewed. A right-sided chylothorax was found in four patients, a left-sided in one, and a bilateral in one. Three patients developed chylothorax after chemotherapy and chest irradiation for malignant diseases (lymphoma in two patients and breast cancer in one), one in the context of lymphangioleiomyomatosis, one due to a non-diagnosed lymphoma, and one after heart transplantation. RESULTS: The mean operative time was 102 min, with an average length of hospital stay of 14 days. Persistent cessation of chylous effusion within 7 days after surgery was observed in 5/6 patients without recurrence during a mean follow-up time of 41 months. One patient with undiagnosed mediastinal lymphoma required re-operation and thoracic duct ligation on day 8 by right-sided thoracotomy due to persistent chylothorax. No 30-day mortality was recorded. Two patients presented postoperative complications including respiratory insufficiency requiring mechanical ventilation in one, and chylous ascites development requiring peritoneo-venous LeVeen shunting in one patient. CONCLUSIONS: Recurrent or persistent non-traumatic chylothorax may be successfully treated by video-assisted right supradiaphragmatic thoracic duct ligation.

Early detection of idiopathic Parkinson's disease based on magnetic resonance imaging

The diagnosis of idiopathic Parkinson's disease (IPD) is entirely clinical. The fact that neuronal damage begins 5-10 years before occurrence of sub-clinical signs, underlines the importance of preclinical diagnosis. A new approach for in-vivo pathophysiological assessment of IPD-related neurodegeneration was implemented based on recently developed neuroimaging methods. It is based on non- invasive magnetic resonance data sensitive to brain tissue property changes that precede macroscopic atrophy in the early stages of IPD. This research aims to determine the brain tissue property changes induced by neurodegeneration that can be linked to clinical phenotypes which will allow us to create a predictive model for early diagnosis in IPD. We hypothesized that the degree of disease progression in IPD patients will have a differential and specific impact on brain tissue properties used to create a predictive model of motor and non-motor impairment in IPD. We studied the potential of in-vivo quantitative imaging sensitive to neurodegeneration- related brain tissue characteristics to detect changes in patients with IPD. We carried out methodological work within the well established SPM8 framework to estimate the sensitivity of tissue probability maps for automated tissue classification for detection of early IPD. We performed whole-brain multi parameter mapping at high resolution followed by voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) comparing healthy subjects to IPD patients. We found a trend demonstrating non-significant tissue property changes in the olfactory bulb area using the MT and R1 parameter with p<0.001. Comparing to the IPD patients, the healthy group presented a bilateral higher MT and R1 intensity in this specific functional region. These results did not correlate with age, severity or duration of disease. We failed to demonstrate any changes with the R2* parameter. We interpreted our findings as demyelination of the olfactory tract, which is clinically represented as anosmia. However, the lack of correlation with duration or severity complicates its implications in the creation of a predictive model of impairment in IPD.

DISTINCT TEMPORALITIES IN THE BREAST CANCER DISEASE PROCESS

Comprehensive approach study aimed understanding the reflections and contrasts between personal time and medical therapy protocol time in the life of a young woman with breast cancer. Addressed as a situational study and grounded in Beth’s life story about getting sick and dying of cancer at age 34, the study’s data collection process employed interviews, observation and medical record analysis. The construction of the analytic-synthetic box based on the chronology of Beth’s clinical progression, treatment phases and temporal perception of occurrences enabled us to point out a linear medical therapy protocol time identified by the diagnosis and treatment sequencing process. On the other hand, Beth’s experienced time was marked by simultaneous and non-linear events that generated suffering resulting from the disease. Such comprehension highlights the need for healthcare professionals to take into account the time experienced by the patient, thus providing an indispensable cancer therapeutic protocol with a personal character.

Proteinaceous infectious behavior in non-pathogenic proteins is controlled by molecular chaperones.

External stresses or mutations may cause labile proteins to lose their distinct native conformations and seek alternatively stable aggregated forms. Molecular chaperones that specifically act on protein aggregates were used here as a tool to address the biochemical nature of stable homo- and hetero-aggregates from non-pathogenic proteins formed by heat-stress. Confirmed by sedimentation and activity measurements, chaperones demonstrated that a single polypeptide chain can form different species of aggregates, depending on the denaturing conditions. Indicative of a cascade reaction, sub-stoichiometric amounts of one fast-aggregating protein strongly accelerated the conversion of another soluble, slow-aggregating protein into insoluble, chaperone-resistant aggregates. Chaperones strongly inhibited seed-induced protein aggregation, suggesting that they can prevent and cure proteinaceous infectious behavior in homo- and hetero-aggregates from common and disease-associated proteins in the cell.

Association of a common vitamin D-binding protein polymorphism with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel diseases (IBDs), Crohn's disease, and ulcerative colitis (UC), are multifactorial disorders, characterized by chronic inflammation of the intestine. A number of genetic components have been proposed to contribute to IBD pathogenesis. In this case-control study, we investigated the association between two common vitamin D-binding protein (DBP) genetic variants and IBD susceptibility. These two single nucleotide polymorphisms (SNPs) in exon 11 of the DBP gene, at codons 416 (GAT>GAG; Asp>Glu) and 420 (ACG>AAG; Thr>Lys), have been previously suggested to play roles in the etiology of other autoimmune diseases. METHODS: Using TaqMan SNP technology, we have genotyped 884 individuals (636 IBD cases and 248 non-IBD controls) for the two DBP variants. RESULTS: On statistical analysis, we observed that the DBP 420 variant Lys is less frequent in IBD cases than in non-IBD controls (allele frequencies, P=0.034; homozygous carrier genotype frequencies, P=0.006). This inverse association between the DBP 420 Lys and the disease remained significant, when non-IBD participants were compared with UC (homozygous carrier genotype frequencies, P=0.022) or Crohn's disease (homozygous carrier genotype frequencies, P=0.016) patients separately. Although the DBP position 416 alone was not found to be significantly associated with IBD, the haplotype DBP_2, consisting of 416 Asp and 420 Lys, was more frequent in the non-IBD population, particularly notably when compared with the UC group (Odds ratio, 4.390). CONCLUSION: Our study adds DBP to the list of potential genes that contribute to the complex genetic etiology of IBD, and further emphasizes the association between vitamin D homeostasis and intestinal inflammation.

Intravitreal chemotherapy for vitreous disease in retinoblastoma revisited: from prohibition to conditional indications.

BACKGROUND: Tumour control of vitreous seeds remains challenging owing to their resistance to radiation and systemic chemotherapy. OBJECTIVE: To describe the short-term efficacy of intravitreal melphalan for vitreous disease in retinoblastoma using a new injection technique and dose. METHODS: This study is a retrospective non-comparative review of 23 consecutive heavily pretreated patients (23 eyes) with active vitreous seeding and eligible for intravitreous chemotherapy (IViC). They received a total of 122 intravitreal injections of melphalan (20-30 μg) given every 7-10 days. The ocular status was objectively monitored under anaesthesia with fundus photography. RESULTS: All patients are alive without evidence of extraocular spread (95% CI 82.19% to 100%). Concomitant treatments, including other chemotherapeutic modalities, were used until complete sterilisation of the retinal seeding source and subretinal seeds. Globe retention was achieved in 87% (20/23) of cases. All retained eyes were in complete remission after a median follow-up period of 22 months (range 9-31 months). The Kaplan-Meier estimate of ocular survival rates at 2 years was 84.14% (95% CI 62.48% to 95.28%). A localised peripheral salt-and-pepper retinopathy was noted in 10 eyes (43%) at the site of injection. CONCLUSIONS: This study reports the first clinically documented case series of patients with retinoblastoma treated with IViC. Despite a possible confounding effect of concomitant chemotherapy prescription using other routes of administration in four of the successfully treated eyes (20%), IViC achieved an unprecedented success rate of tumour control in the presence of vitreous seeding. Of note, none of the treated eyes required external beam irradiation to control the vitreous seeding. Further studies are required to assess IViC retinal toxicity and to better delineate its role in the management of retinoblastoma.

Clinical characteristics and outcome of patients admitted to a medico-surgical ICU requiring non invasive ventilation (NIV) for hypercapnic respiratory failure

Introduction: Because it decreases intubation rate and mortality, NIV has become first-line treatment in case of hypercapnic respiratory failure (HRF). Whether this approach is equally successful for all categories of HRF patients is however debated. We assessed if any clinical characteristics of HRF patients were associated with NIV intensity, success, and outcome, in order to identify prognostic factors. Methods: Retrospective analysis of the clinical database (clinical information system and MDSi) of patients consecutively admitted to our medico-surgical ICU, presenting with HRF (defined as PaCO2 >50 mm Hg), and receiving NIV between January 2009 and December 2010. Demographic data, medical diagnoses (including documented chronic lung disease), reason for ICU hospitalization, recent surgical interventions, SAPS II and McCabe scores were extracted from the database. Total duration of NIV and the need for tracheal intubation during the 5 days following the first hypercapnia documentation, as well as ICU and hospital mortality were recorded. Results are reported as median [IQR]. Comparisons with Chi2 or Kruskal-Wallis tests, p <0.05 (*). Results: 164 patients were included, 45 (27.4%) of whom were intubated after 10 [2-34] hours, after having received 7 [2-19] hours of NIV. NIV successful patients received 15 [5-22] hours of NIV for up to 5 days. Intubation was correlated with increased ICU (20% vs. 3%, p <0.001) and hospital (46.7% vs. 30.2, p >0.05) mortality. Conclusions: A majority of patients requiring NIV for hypercapnic respiratory failure in our ICU have no diagnosed chronic pulmonary disease. These patients tend to have increased ICUand hospital mortality. The majority of patients were non-surgical, a feature correlated with increased hospital mortality. Beside usual predictors of severity such as age and SAPS II, absence of diagnosed chronic pulmonary disease and non-operative state appear to be associated with increased mortality. Further studies should explore whether these patients are indeed more prone to an adverse outcome and which therapeutic strategies might contribute to alter this course.

Sténose oesophagienne non-néoplasique: pas toujours si bénigne [Non-neoplastic esophageal stenosis: not always so benign].

Esophageal intramural pseudodiverticulosis is a rare pathology whose etiology is unknown, but which is frequently associated with three highly prevalent entities: esophageal reflux disease, esophageal candidosis and alcoholic esophagitis. With conservative treatment the course of these pathologies is usually benign. However, some severe cases are resistant to conservative treatment and may require more aggressive management. We here present the case of patient suffering from a severe esophagitis complicated by chronic mediastinitis with life-threatening repercussions, requiring esophagectomy as treatment.

Cell locations for AQP1, AQP4 and 9 in the non-human primate brain.

The presence of three water channels (aquaporins, AQP), AQP1, AQP4 and AQP9 were observed in normal brain and several rodent models of brain pathologies. Little is known about AQP distribution in the primate brain and its knowledge will be useful for future testing of drugs aimed at preventing brain edema formation. We studied the expression and cellular distribution of AQP1, 4 and 9 in the non-human primate brain. The distribution of AQP4 in the non-human primate brain was observed in perivascular astrocytes, comparable to the observation made in the rodent brain. In contrast with rodent, primate AQP1 is expressed in the processes and perivascular endfeet of a subtype of astrocytes mainly located in the white matter and the glia limitans, possibly involved in water homeostasis. AQP1 was also observed in neurons innervating the pial blood vessels, suggesting a possible role in cerebral blood flow regulation. As described in rodent, AQP9 mRNA and protein were detected in astrocytes and in catecholaminergic neurons. However additional locations were observed for AQP9 in populations of neurons located in several cortical areas of primate brains. This report describes a detailed study of AQP1, 4 and 9 distributions in the non-human primate brain, which adds to the data already published in rodent brains. This relevant species differences have to be considered carefully to assess potential drugs acting on AQPs non-human primate models before entering human clinical trials.

Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The Second ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on management of patients with non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, early stage disease, locally advanced disease and advanced (metastatic) disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on recommendations for pathology and molecular biomarkers in relation to the diagnosis of lung cancer, primarily non-small-cell carcinomas.