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Showing papers by "Catholic University of the Sacred Heart published in 2012"


Journal ArticleDOI
TL;DR: In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glucose control than did medical therapy and preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures.
Abstract: Methods In this single-center, nonblinded, randomized, controlled trial, 60 patients between the ages of 30 and 60 years with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 35 or more, a history of at least 5 years of diabetes, and a glycated hemoglobin level of 7.0% or more were randomly assigned to receive conventional medical therapy or undergo either gastric bypass or biliopancreatic diversion. The primary end point was the rate of diabetes remission at 2 years (defined as a fasting glucose level of <100 mg per deciliter [5.6 mmol per liter] and a glycated hemoglobin level of <6.5% in the absence of pharmacologic therapy). Results At 2 years, diabetes remission had occurred in no patients in the medical-therapy group versus 75% in the gastric-bypass group and 95% in the biliopancreatic-diversion group (P<0.001 for both comparisons). Age, sex, baseline BMI, duration of diabetes, and weight changes were not significant predictors of diabetes remission at 2 years or of improvement in glycemia at 1 and 3 months. At 2 years, the average baseline glycated hemoglobin level (8.65±1.45%) had decreased in all groups, but patients in the two surgical groups had the greatest degree of improvement (average glycated hemoglobin levels, 7.69±0.57% in the medical-therapy group, 6.35±1.42% in the gastric-bypass group, and 4.95±0.49% in the biliopancreatic-diversion group). Conclusions In severely obese patients with type 2 diabetes, bariatric surgery resulted in better glu cose control than did medical therapy. Preoperative BMI and weight loss did not predict the improvement in hyperglycemia after these procedures. (Funded by Catholic University of Rome; ClinicalTrials.gov number, NCT00888836.)

1,264 citations


Journal ArticleDOI
TL;DR: This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice.
Abstract: Our objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition. The European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2 days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision. The Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1 week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO2/FiO2 thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy. This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice.

1,074 citations


Journal ArticleDOI
TL;DR: To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.
Abstract: Background The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. Methods In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P Conclusions KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.

861 citations


Journal ArticleDOI
Paul A. Northcott1, Paul A. Northcott2, David Shih1, John Peacock1, Livia Garzia1, A. Sorana Morrissy1, Thomas Zichner, Adrian M. Stütz, Andrey Korshunov2, Jüri Reimand1, Steven E. Schumacher3, Rameen Beroukhim4, Rameen Beroukhim3, David W. Ellison, Christian R. Marshall1, Anath C. Lionel1, Stephen C. Mack1, Adrian M. Dubuc1, Yuan Yao1, Vijay Ramaswamy1, Betty Luu1, Adi Rolider1, Florence M.G. Cavalli1, Xin Wang1, Marc Remke1, Xiaochong Wu1, Readman Chiu5, Andy Chu5, Eric Chuah5, Richard Corbett5, Gemma Hoad5, Shaun D. Jackman5, Yisu Li5, Allan Lo5, Karen Mungall5, Ka Ming Nip5, Jenny Q. Qian5, Anthony Raymond5, Nina Thiessen5, Richard Varhol5, Inanc Birol5, Richard A. Moore5, Andrew J. Mungall5, Robert A. Holt5, Daisuke Kawauchi, Martine F. Roussel, Marcel Kool2, David T.W. Jones2, Hendrick Witt6, Africa Fernandez-L7, Anna Kenney8, Robert J. Wechsler-Reya9, Peter B. Dirks1, Tzvi Aviv1, Wiesława Grajkowska, Marta Perek-Polnik, Christine Haberler10, Olivier Delattre11, Stéphanie Reynaud11, François Doz11, Sarah S. Pernet-Fattet12, Byung Kyu Cho13, Seung-Ki Kim13, Kyu-Chang Wang13, Wolfram Scheurlen, Charles G. Eberhart14, Michelle Fèvre-Montange15, Anne Jouvet15, Ian F. Pollack16, Xing Fan17, Karin M. Muraszko17, G. Yancey Gillespie18, Concezio Di Rocco19, Luca Massimi19, Erna M.C. Michiels20, Nanne K. Kloosterhof20, Pim J. French20, Johan M. Kros20, James M. Olson21, Richard G. Ellenbogen22, Karel Zitterbart23, Leos Kren23, Reid C. Thompson8, Michael K. Cooper8, Boleslaw Lach24, Boleslaw Lach25, Roger E. McLendon26, Darell D. Bigner26, Adam M. Fontebasso27, Steffen Albrecht28, Steffen Albrecht27, Nada Jabado27, Janet C. Lindsey29, Simon Bailey29, Nalin Gupta30, William A. Weiss30, László Bognár31, Almos Klekner31, Timothy E. Van Meter, Toshihiro Kumabe32, Teiji Tominaga32, Samer K. Elbabaa33, Jeffrey R. Leonard34, Joshua B. Rubin34, Linda M. Liau35, Erwin G. Van Meir36, Maryam Fouladi37, Hideo Nakamura38, Giuseppe Cinalli, Miklós Garami39, Peter Hauser39, Ali G. Saad40, Achille Iolascon41, Shin Jung42, Carlos Gilberto Carlotti43, Rajeev Vibhakar44, Young Shin Ra45, Shenandoah Robinson, Massimo Zollo41, Claudia C. Faria1, Jennifer A. Chan46, Michael J. Levy21, Poul H. Sorensen5, Matthew Meyerson3, Scott L. Pomeroy3, Yoon Jae Cho47, Gary D. Bader1, Uri Tabori1, Cynthia Hawkins1, Eric Bouffet1, Stephen W. Scherer1, James T. Rutka1, David Malkin1, Steven C. Clifford29, Steven J.M. Jones5, Jan O. Korbel, Stefan M. Pfister6, Stefan M. Pfister2, Marco A. Marra5, Michael D. Taylor1 
02 Aug 2012-Nature
TL;DR: Somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas are reported, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Groups 4, which suggest future avenues for rational, targeted therapy.
Abstract: Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

749 citations


Journal ArticleDOI
TL;DR: Data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5+ ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration.
Abstract: The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high-dose radiation injury. After irradiation, however, the normally quiescent Bmi1+ ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1+ ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5+ ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration.

730 citations


Journal ArticleDOI
07 Sep 2012-Science
TL;DR: In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs, and a fusion gene detected in a small subset of human brain tumors encodes a potentially druggable target.
Abstract: The brain tumor glioblastoma multiforme (GBM) is among the most lethal forms of human cancer. Here, we report that a small subset of GBMs (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes (FGFR1 or FGFR3) to the transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3, respectively. The FGFR-TACC fusion protein displays oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrects the aneuploidy, and oral administration of an FGFR inhibitor prolongs survival of mice harboring intracranial FGFR3-TACC3–initiated glioma. FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition.

679 citations


Journal ArticleDOI
TL;DR: By combining measurements of enzyme activity in soil with expression (transcriptomics and proteomics) of genes, encoding the relative enzymes may contribute to understanding the mode and timing of microbial communities’ responses to substrate availability and persistence and stabilization of enzymes in the soil.
Abstract: It is still problematic to use enzyme activities as indicators of soil functions because: (1) enzyme assays determine potential and not real enzyme activities; (2) the meaning of measured enzyme activities is not known; (3) the assumption that a single enzyme activity is an indicator of nutrient dynamics in soil neglects that the many enzyme activities are involved in such dynamic processes; (4) spatio-temporal variations in natural environments are not always considered when measuring enzyme activities; and (5) many direct and indirect effects make difficult the interpretation of the response of the enzyme activity to perturbations, changes in the soil management, changes in the plant cover of soil, etc. This is the first review discussing the links between enzyme-encoding genes and the relative enzyme activity of soil. By combining measurements of enzyme activity in soil with expression (transcriptomics and proteomics) of genes, encoding the relative enzymes may contribute to understanding the mode and timing of microbial communities’ responses to substrate availability and persistence and stabilization of enzymes in the soil.

485 citations


Journal ArticleDOI
Jean Bousquet1, Holger J. Schünemann2, B. Samolinski3, Pascal Demoly  +233 moreInstitutions (127)
TL;DR: Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
Abstract: Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

453 citations



Journal ArticleDOI
TL;DR: How hormetic dose responses are mediated for endogenous cellular defense pathways including sirtuin, Nrfs and related pathways that integrate adaptive stress responses in the prevention of neurodegenerative diseases is described in mechanistic detail.

361 citations


Journal ArticleDOI
TL;DR: Some non-motor symptoms improve after DBS, partly because of motor benefit or reduction of drug treatment, and partly as a direct effect of stimulation.
Abstract: Summary Deep brain stimulation (DBS) is an established procedure for the symptomatic treatment of Parkinson's disease. Several deep brain nuclei have been stimulated, producing a wide range of effects on the motor and non-motor symptoms of Parkinson's disease. Long-term, high-quality evidence is available for stimulation of the subthalamic nucleus and globus pallidus internus, both of which uniformly improve motor features, and for stimulation of the thalamic ventralis intermedius, which improves tremor. Short-term data are available for stimulation of other deep brain targets, such as the pedunculopontine nucleus and the centremedian/parafascicular thalamic complex. Some non-motor symptoms improve after DBS, partly because of motor benefit or reduction of drug treatment, and partly as a direct effect of stimulation. More evidence on the effects of DBS on non-motor symptoms is needed and specifically designed studies are warranted.


Journal ArticleDOI
TL;DR: These Guidelines have been a big effort of SOSORT to paint the actual situation of CTIS, starting from the evidence, and filling all the gray areas using a scientific method, and it is possible to understand the lack of research in general on CTIS.
Abstract: The International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT), that produced its first Guidelines in 2005, felt the need to revise them and increase their scientific quality. The aim is to offer to all professionals and their patients an evidence-based updated review of the actual evidence on conservative treatment of idiopathic scoliosis (CTIS). All types of professionals (specialty physicians, and allied health professionals) engaged in CTIS have been involved together with a methodologist and a patient representative. A review of all the relevant literature and of the existing Guidelines have been performed. Documents, recommendations, and practical approach flow charts have been developed according to a Delphi procedure. A methodological and practical review has been made, and a final Consensus Session was held during the 2011 Barcelona SOSORT Meeting. The contents of the document are: methodology; generalities on idiopathic scoliosis; approach to CTIS in different patients, with practical flow-charts; literature review and recommendations on assessment, bracing, physiotherapy, Physiotherapeutic Specific Exercises (PSE) and other CTIS. Sixty-five recommendations have been given, divided in the following topics: Bracing (20 recommendations), PSE to prevent scoliosis progression during growth (8), PSE during brace treatment and surgical therapy (5), Other conservative treatments (3), Respiratory function and exercises (3), Sports activities (6), Assessment (20). No recommendations reached a Strength of Evidence level I; 2 were level II; 7 level III; and 20 level IV; through the Consensus procedure 26 reached level V and 10 level VI. The Strength of Recommendations was Grade A for 13, B for 49 and C for 3; none had grade D. These Guidelines have been a big effort of SOSORT to paint the actual situation of CTIS, starting from the evidence, and filling all the gray areas using a scientific method. According to results, it is possible to understand the lack of research in general on CTIS. SOSORT invites researchers to join, and clinicians to develop good research strategies to allow in the future to support or refute these recommendations according to new and stronger evidence.

Journal ArticleDOI
TL;DR: This observational study, the first ever formally to appraise OCT guidance for PCI decision-making, suggests that the use of OCT can improve clinical outcomes of patients undergoing PCI.
Abstract: Aims Angiographic guidance for percutaneous coronary intervention (PCI) has substantial limitations. The superior spatial resolution of optical coherence tomography (OCT) could translate into meaningful clinical benefits. We aimed to compare angiographic guidance alone versus angiographic plus OCT guidance for PCI. Methods and results Patients undergoing PCI with angiographic plus OCT guidance (OCT group) were compared with matched patients undergoing PCI with angiographic only guidance (Angio group) within 30 days. The primary endpoint was the one-year rate of cardiac death or myocardial infarction (MI). A total of 670 patients were included, 335 in the OCT group and 335 in the Angio group. OCT disclosed adverse features requiring further interventions in 34.7%. Unadjusted analyses showed that the OCT group had a significantly lower one-year risk of cardiac death (1.2% vs. 4.5%, p=0.010), cardiac death or MI (6.6% vs. 13.0%, p=0.006), and the composite of cardiac death, MI, or repeat revascularisation (9.6% vs. 14.8%, p=0.044). Angiographic plus OCT guidance was associated with a significantly lower risk of cardiac death or MI even at extensive multivariable analysis adjusting for baseline and procedural differences between the groups (OR=0.49 [0.25-0.96], p=0.037) and at propensity-score adjusted analyses. Conclusions This observational study, the first ever formally to appraise OCT guidance for PCI decision-making, suggests that the use of OCT can improve clinical outcomes of patients undergoing PCI.

Journal ArticleDOI
TL;DR: Whether the main characteristics of the activity evoked by single- and paired-pulse and repetitive TMS, can be accounted by the interaction of the induced currents in the brain with the key anatomic features of a simple cortical circuit, which represents the minimum architecture necessary for capturing the most essential cortical input-output operations of neocortex is evaluated.

Journal ArticleDOI
TL;DR: The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling.
Abstract: This article is the second of a two-part publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided Trucut biopsy. The first part (the Clinical Guideline) focused on the results obtained with EUS-guided sampling, and the role of this technique in patient management, and made recommendations on circumstances that warrant its use. The current Technical Guideline discusses issues related to learning, techniques, and complications of EUS-guided sampling, and to processing of specimens. Technical issues related to maximizing the diagnostic yield (e.g., rapid on-site cytopathological evaluation, needle diameter, microcore isolation for histopathological examination, and adequate number of needle passes) are discussed and recommendations are made for various settings, including solid and cystic pancreatic lesions, submucosal tumors, and lymph nodes. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling. A two-page executive summary of evidence statements and recommendations is provided.

Journal ArticleDOI
TL;DR: The interRAI LTCF appears to be a reliable instrument that enables the creation of databases that can be used to govern the provision of long-term care across different health systems in Europe, to answer relevant research and policy questions and to compare characteristics of NH residents across countries, languages and cultures.
Abstract: Aims of the present study are the following: 1. to describe the rationale and methodology of the Services and Health for Elderly in Long TERm care (SHELTER) study, a project funded by the European Union, aimed at implementing the interRAI instrument for Long Term Care Facilities (interRAI LTCF) as a tool to assess and gather uniform information about nursing home (NH) residents across different health systems in European countries; 2. to present the results about the test-retest and inter-rater reliability of the interRAI LTCF instrument translated into the languages of participating countries; 3 to illustrate the characteristics of NH residents at study entry. A 12 months prospective cohort study was conducted in 57 NH in 7 EU countries (Czech Republic, England, Finland, France, Germany, Italy, The Netherlands) and 1 non EU country (Israel). Weighted kappa coefficients were used to evaluate the reliability of interRAI LTCF items. Mean age of 4156 residents entering the study was 83.4 ± 9.4 years, 73% were female. ADL disability and cognitive impairment was observed in 81.3% and 68.0% of residents, respectively. Clinical complexity of residents was confirmed by a high prevalence of behavioral symptoms (27.5% of residents), falls (18.6%), pressure ulcers (10.4%), pain (36.0%) and urinary incontinence (73.5%). Overall, 197 of the 198 the items tested met or exceeded standard cut-offs for acceptable test-retest and inter-rater reliability after translation into the target languages. The interRAI LTCF appears to be a reliable instrument. It enables the creation of databases that can be used to govern the provision of long-term care across different health systems in Europe, to answer relevant research and policy questions and to compare characteristics of NH residents across countries, languages and cultures.

Journal ArticleDOI
TL;DR: The understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS.
Abstract: Fragile X syndrome (FXS) is the most frequent form of inherited intellectual disability and is also linked to other neurologic and psychiatric disorders. FXS is caused by a triplet expansion that inhibits expression of the FMR1 gene; the gene product, FMRP, regulates mRNA metabolism in the brain and thus controls the expression of key molecules involved in receptor signaling and spine morphology. While there is no definitive cure for FXS, the understanding of FMRP function has paved the way for rational treatment designs that could potentially reverse many of the neurobiological changes observed in FXS. Additionally, behavioral, pharmacological, and cognitive interventions can raise the quality of life for both patients and their families.


Journal ArticleDOI
TL;DR: Existing evidence suggests a role for glutathione metabolism, the transmethylation cycle, and the transsulfuration pathway, although these findings should be interpreted with caution, and larger, more standardized studies are warranted.

Journal ArticleDOI
TL;DR: It is suggested that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.
Abstract: Summary Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC-1a, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.

Journal ArticleDOI
TL;DR: Excessive polypharmacy was directly associated not only with presence of chronic diseases but also with depression, and specific symptoms, age, functional, and cognitive status among nursing home residents in Europe.
Abstract: Background: This study assesses prevalence and patients characteristics related to polypharmacy in a sample of nursing home residents. Methods: We conducted a cross-sectional analysis on 4,023 nursing home residents participating to the Services and Health for Elderly in Long TERm care (SHELTER) project, a study collecting information on residents admitted to 57 nursing home in 8 countries. Data were collected using the interRAI instrument for long-term care facilities. Polypharmacy status was categorized in 3 groups: non-polypharmacy (0-4 drugs), polypharmacy (5-9 drugs) and excessive polypharmacy (≥ 10 drugs). Results: Polypharmacy was observed in 2,000 (49.7%) residents and excessive polypharmacy in 979 (24.3%) residents. As compared with non-polypharmacy, excessive polypharmacy was directly associated not only with presence of chronic diseases but also with depression (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.38-2.37), pain (OR 2.31; 95% CI 1.80-2.97), dyspnoea (OR 2.29; 95% CI 1.61-3.27), and gastrointestinal symptoms (OR 1.73; 95% CI 1.35-2.21). An inverse association with excessive polypharmacy was shown for age (OR for 10 years increment 0.85; 95% CI 0.74-0.96), activities of daily living disability (OR for assistance required vs independent 0.90; 95% CI 0.64-1.26; OR for dependent vs independent 0.59; 95% CI 0.40-0.86), and cognitive impairment (OR for mild or moderate vs intact 0.64; 95% CI 0.47-0.88; OR for severe vs intact 0.39; 95% CI 0.26-0.57). Conclusions: Polypharmacy and excessive polypharmacy are common among nursing home residents in Europe. Determinants of polypharmacy status include not only comorbidity but also specific symptoms, age, functional, and cognitive status.

Journal ArticleDOI
TL;DR: The authors' data showed that patient engagement is gaining increasing attention by all the academic disciplines involved in health research with a predominance of medicine and nursing, and there is still a lack of an evidence-based theoretical foundation of the construct as well as of the organizational dimensions that foster it.
Abstract: Patients' engagement in healthcare is at the forefront of policy and research practice and is now widely recognized as a critical ingredient for high-quality healthcare system This study aims to analyze the current academic literature (from 2002 to 2012) about patient engagement by using bibliometric and qualitative content analyses Extracting data from the electronic databases more likely to cover the core research publications in health issues, the number of yearly publications, the most productive countries, and the scientific discipline dealing with patient engagement were quantitatively described Qualitative content analysis of the most cited articles was conducted to distinguish the core themes Our data showed that patient engagement is gaining increasing attention by all the academic disciplines involved in health research with a predominance of medicine and nursing Engaging patients is internationally recognized as a key factor in improving health service delivery and quality Great attention is up to now paid to the clinical and organizational outcomes of engagement, whereas there is still a lack of an evidence-based theoretical foundation of the construct as well as of the organizational dimensions that foster it

Journal ArticleDOI
TL;DR: This research presents a meta-analyses of the immune system’s response to chemotherapy, which shows clear patterns of decline in the immune systems of patients with symptomatic oncologists and patients with a history of liver disease.
Abstract: a Department of Digestive and Liver Disease, Ospedale Sant’Andrea, Rome , Italy; b Department of Oncology, Royal Free University UFR Bichat-Beaujon-Louis Mourier, Colombes , France; c Digestive Oncology, University Hospital Gasthuisberg/Leuven, Leuven , Belgium; d Institute of Pathology, Catholic University – Policlinic A. Gemelli, Rome , Italy; e Department of Endocrinology, Medical University of Silesia, Katowice , Poland; f Department of Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen , Denmark; g Department of Pathology, Tohoku University Graduate School of Medicine, Sendai , Japan; h Department of Internal Medicine and Gastroenterology, St. Orsola Hospital, University of Bologna, Bologna , Italy; i Institut Catala d’Oncologia (IDIBELL), Barcelona , Spain; j Department of Gastroenterology, Beaujon Hospital, Clichy , France

Journal ArticleDOI
TL;DR: This version is an updated version of the guideline that was published in 2012 and updated in 2014 and needs to be targeted, multimodal and performed in a step-wise procedure requiring an interdisciplinary approach.
Abstract: Pruritus is a frequent symptom in medicine. Population-based studies show that every 5th person in the general population has suffered from chronic pruritus at least once in the lifetime with a 12-month incidence of 7%. In patient populations its frequency is much higher depending on the underlying cause, ranging from around 25% in haemodialysis patients to 100% in skin diseases such as urticaria and atopic dermatitis (AD). Pruritus may be the result of a dermatological or non-dermatological disease. Especially in non-diseased skin it may be caused by systemic, neurological or psychiatric diseases, as well as being a side effect of medications. In a number of cases chronic pruritus may be of multifactorial origin. Pruritus needs a precise diagnostic work-up. Management of chronic pruritus comprises treatment of the underlying disease and topical treatment modalities, including symptomatic antipruritic treatment, ultraviolet phototherapy and systemic treatment. Treating chronic pruritus needs to be targeted, multimodal and performed in a step-wise procedure requiring an interdisciplinary approach. We present the updated and consensus based (S2k) European guideline on chronic pruritus by a team of European pruritus experts from different disciplines. This version is an updated version of the guideline that was published in 2012 and updated in 2014 (www.euroderm.org).

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TL;DR: In this article, a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used for species identification through direct surface analysis of the fungal culture.

Journal ArticleDOI
TL;DR: The results indicate that LFI and LFI-related parameters could be used to identify cows at risk in the transition period toward an improved farm management and indicates that disease cases in periparturient, high-yielding dairy cows are correlated with signs of accentuated IL-6 response and other markers of inflammatory phenomena.

Journal ArticleDOI
TL;DR: In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity, and these accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicions of neuroendocrine tumours.
Abstract: Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. Results: Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91–95%) and 91% (95% CI: 82–97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.


Journal ArticleDOI
TL;DR: It is demonstrated that Mtb alters the autophagic machinery through the ESX-1 system, and thereby opens new exciting perspectives to better understand the relationship between Mtb virulence and its ability to escape the DC-mediated immune response.
Abstract: Emerging evidence points to an important role of autophagy in the immune response mediated by dendritic cells (DC) against Mycobacterium tuberculosis (Mtb) Since current vaccination based on Bacillus Calmette-Guerin (BCG) is unable to stop the tuberculosis epidemic, a deeper comprehension of the alterations induced by Mtb in DC is essential for setting new vaccine strategies Here, we compared the capacity of virulent (H37Rv) and avirulent (H37Ra) Mtb strains as well as BCG to modulate autophagy in human primary DC We found that Mtb H37Rv impairs autophagy at the step of autophagosome-lysosome fusion In contrast, neither Mtb H37Ra nor BCG strains were able to hamper autophagosome maturation Both these attenuated strains have a functional inhibition of the 6kD early secreted antigenic target ESAT-6, an effector protein of the ESAT-6 Secretion System-1(ESX-1)/type VII secretion system Notably, the ability to inhibit autophagy was fully restored in recombinant BCG and Mtb H37Ra strains in which ESAT-6 secretion was re-established by genetic complementation using either the ESX-1 region from Mtb (BCG::ESX-1) or the PhoP gene (Mtb H37Ra::PhoP), a regulator of ESAT-6 secretion Importantly, the autophagic block induced by Mtb was overcome by rapamycin treatment leading to an increased interleukin-12 expression and, in turn, to an enhanced capacity to expand a Th1-oriented response Collectively, our study demonstrated that Mtb alters the autophagic machinery through the ESX-1 system, and thereby opens new exciting perspectives to better understand the relationship between Mtb virulence and its ability to escape the DC-mediated immune response