Showing papers by "Catholic University of the Sacred Heart published in 2014"

Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic

Abstract: An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

Cryptogenic stroke and underlying atrial fibrillation

Abstract: Background Current guidelines recommend at least 24 hours of electrocardiographic (ECG) monitoring after an ischemic stroke to rule out atrial fibrillation. However, the most effective duration and type of monitoring have not been established, and the cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in 20 to 40% of cases (cryptogenic stroke). Detection of atrial fibrillation after cryptogenic stroke has therapeutic implications. Methods We conducted a randomized, controlled study of 441 patients to assess whether long-term monitoring with an insertable cardiac monitor (ICM) is more effective than conventional follow-up (control) for detecting atrial fibrillation in patients with cryptogenic stroke. Patients 40 years of age or older with no evidence of atrial fibrillation during at least 24 hours of ECG monitoring underwent randomization within 90 days after the index event. The primary end point was the time to first detection of atrial fibrillation (lasting >30 seconds) within 6 months. Among the secondary end points was the time to first detection of atrial fibrillation within 12 months. Data were analyzed according to the intention-to-treat principle. Results By 6 months, atrial fibrillation had been detected in 8.9% of patients in the ICM group (19 patients) versus 1.4% of patients in the control group (3 patients) (hazard ratio, 6.4; 95% confidence interval [CI], 1.9 to 21.7; P<0.001). By 12 months, atrial fib rillation had been detected in 12.4% of patients in the ICM group (29 patients) versus 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6 to 20.8; P<0.001). Conclusions ECG monitoring with an ICM was superior to conventional follow-up for detecting atrial fibrillation after cryptogenic stroke. (Funded by Medtronic; CRYSTAL AF ClinicalTrials.gov number, NCT00924638.)

Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS)

Abstract: OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.

Lanreotide in metastatic enteropancreatic neuroendocrine tumors.

Abstract: Background Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. Methods We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor–positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. Results Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant betweengroup differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). Conclusions Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.)

International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer

Abstract: Purpose To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. Methods SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. Results GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensit...

Ancient human genomes suggest three ancestral populations for present-day Europeans

Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

Restoring Natural Sensory Feedback in Real-Time Bidirectional Hand Prostheses

Abstract: Hand loss is a highly disabling event that markedly affects the quality of life. To achieve a close to natural replacement for the lost hand, the user should be provided with the rich sensations that we naturally perceive when grasping or manipulating an object. Ideal bidirectional hand prostheses should involve both a reliable decoding of the user's intentions and the delivery of nearly "natural" sensory feedback through remnant afferent pathways, simultaneously and in real time. However, current hand prostheses fail to achieve these requirements, particularly because they lack any sensory feedback. We show that by stimulating the median and ulnar nerve fascicles using transversal multichannel intrafascicular electrodes, according to the information provided by the artificial sensors from a hand prosthesis, physiologically appropriate (near-natural) sensory information can be provided to an amputee during the real-time decoding of different grasping tasks to control a dexterous hand prosthesis. This feedback enabled the participant to effectively modulate the grasping force of the prosthesis with no visual or auditory feedback. Three different force levels were distinguished and consistently used by the subject. The results also demonstrate that a high complexity of perception can be obtained, allowing the subject to identify the stiffness and shape of three different objects by exploiting different characteristics of the elicited sensations. This approach could improve the efficacy and "life-like" quality of hand prostheses, resulting in a keystone strategy for the near-natural replacement of missing hands.

Bone substitutes in orthopaedic surgery: from basic science to clinical practice

Abstract: Bone substitutes are being increasingly used in surgery as over two millions bone grafting procedures are performed worldwide per year. Autografts still represent the gold standard for bone substitution, though the morbidity and the inherent limited availability are the main limitations. Allografts, i.e. banked bone, are osteoconductive and weakly osteoinductive, though there are still concerns about the residual infective risks, costs and donor availability issues. As an alternative, xenograft substitutes are cheap, but their use provided contrasting results, so far. Ceramic-based synthetic bone substitutes are alternatively based on hydroxyapatite (HA) and tricalcium phosphates, and are widely used in the clinical practice. Indeed, despite being completely resorbable and weaker than cortical bone, they have exhaustively proved to be effective. Biomimetic HAs are the evolution of traditional HA and contains ions (carbonates, Si, Sr, Fl, Mg) that mimic natural HA (biomimetic HA). Injectable cements represent another evolution, enabling mininvasive techniques. Bone morphogenetic proteins (namely BMP2 and 7) are the only bone inducing growth factors approved for human use in spine surgery and for the treatment of tibial nonunion. Demineralized bone matrix and platelet rich plasma did not prove to be effective and their use as bone substitutes remains controversial. Experimental cell-based approaches are considered the best suitable emerging strategies in several regenerative medicine application, including bone regeneration. In some cases, cells have been used as bioactive vehicles delivering osteoinductive genes locally to achieve bone regeneration. In particular, mesenchymal stem cells have been widely exploited for this purpose, being multipotent cells capable of efficient osteogenic potential. Here we intend to review and update the alternative available techniques used for bone fusion, along with some hints on the advancements achieved through the experimental research in this field.

Coronary microvascular dysfunction: an update

Abstract: Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy

Environmental Regulation and Competitiveness: Empirical Evidence on the Porter Hypothesis from European Manufacturing Sectors

Abstract: This paper represents an empirical investigation of the “weak” and “strong” Porter Hypothesis (PH) focusing on the manufacturing sectors of European countries between 1997 and 2009. By and large, the literature has analyzed the impact of environmental regulation on innovation and on productivity generally in separate analyses and mostly focusing on the USA. The few existing studies focusing on Europe investigate the effect of environmental regulation either on green innovation or on performance indicators such as exports. We instead look at overall innovation and productivity impact that are the most relevant indicators for the “strong” PH. This approach allows us to account for potential opportunity costs of induced innovations. As a proxy of environmental policy stringency we use pollution abatement and control expenditures (PACE), which represent one of the few indicators available at the sectoral level. We remedy upon its main drawback, that of potential endogeneity of PACE, by adopting an instrumental variable estimation approach. We find evidence of a positive impact of environmental regulation on the output of innovation activity, as proxied by patents, thus providing support in favor of the “weak” PH in line with most of the literature. On the other front, we find no evidence in favor or against the “strong” PH, as productivity appears to be unaffected by the degree of pollution control and abatement efforts.

Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches

Abstract: Bone fusion represents a challenge in the orthopedics practice, being especially indicated for spine disorders. Spinal fusion can be defined as the bony union between two vertebral bodies obtained through the surgical introduction of an osteoconductive, osteoinductive, and osteogenic compound. Autogenous bone graft provides all these three qualities and is considered the gold standard. However, a high morbidity is associated with the harvest procedure. Intensive research efforts have been spent during the last decades to develop new approaches and technologies for successful spine fusion. In recent years, cell and gene therapies have attracted great interest from the scientific community. The improved knowledge of both mesenchymal stem cell biology and osteogenic molecules allowed their use in regenerative medicine, representing attractive approaches to achieve bone regeneration also in spinal surgery applications. In this review we aim to describe the developing gene- and cell-based bone regenerative approaches as promising future trends in spine fusion.

The frailty phenotype and the frailty index: different instruments for different purposes

Abstract: The integration of frailty measures in clinical practice is crucial for the development of interventions against disabling conditions in older persons. The frailty phenotype (proposed and validated by Fried and colleagues in the Cardiovascular Health Study) and the Frailty Index (proposed and validated by Rockwood and colleagues in the Canadian Study of Health and Aging) represent the most known operational definitions of frailty in older persons. Unfortunately, they are often wrongly considered as alternatives and/or substitutables. These two instruments are indeed very different and should rather be considered as complementary. In the present paper, we discuss about the designs and rationals of the two instruments, proposing the correct ways for having them implemented in the clinical setting.

A Large Cross-Sectional Survey Investigating the Knowledge of Cervical Cancer Risk Aetiology and the Predictors of the Adherence to Cervical Cancer Screening Related to Mass Media Campaign

Abstract: Objectives. The aims of this study were to compare the characteristics of women who got a Pap-test during the mass media campaign, carried out in an Italian region by broadcasts advertising, and two years later and to identify the determinants of knowledge of cervical cancer etiology and of the adherence to the mass media campaign. Methods. A cross-sectional survey was carried out through a self-administered questionnaire. Results. A total of 8570 randomly selected women were surveyed, 823 of these had a Pap-test during the mass media campaign period and 7747 two years later. Higher educational level, being not married, and living in urban areas were the main independent characteristics associated with a higher level of knowledge of cervical cancer etiology, although a previous treatment following a Pap smear abnormality was the strongest predictor (OR = 2.88; 95% CI: 2.43–3.41). During the campaign period women had the Pap-test more frequently as a consequence of the mass media campaign (OR = 8.28; 95% CI; 5.51–12.45). Conclusions. Mass media campaign is a useful tool to foster cervical screening compliance; however, its short-term effect suggests repeating it regularly.

Ancient human genomes suggest three ancestral populations for present-day Europeans

Abstract: We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had ∼44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.

Nasal high-flow versus Venturi mask oxygen therapy after extubation. Effects on oxygenation, comfort, and clinical outcome

Abstract: Rationale Oxygen is commonly administered after extubation. Although several devices are available, data about their clinical efficacy are scarce. Objectives To compare the effects of the Venturi mask and the nasal high-flow (NHF) therapy on PaO2/FiO2SET ratio after extubation. Secondary endpoints were to assess effects on patient discomfort, adverse events, and clinical outcomes. Methods Randomized, controlled, open-label trial on 105 patients with a PaO2/FiO2 ratio less than or equal to 300 immediately before extubation. The Venturi mask (n = 52) or NHF (n = 53) were applied for 48 hours postextubation. Measurements and main results PaO2/FiO2SET, patient discomfort caused by the interface and by symptoms of airways dryness (on a 10-point numerical rating scale), interface displacements, oxygen desaturations, need for ventilator support, and reintubation were assessed up to 48 hours after extubation. From the 24th hour, PaO2/FiO2SET was higher with the NHF (287 ± 74 vs. 247 ± 81 at 24 h; P = 0.03). Discomfort related both to the interface and to airways dryness was better with NHF (respectively, 2.6 ± 2.2 vs. 5.1 ± 3.3 at 24 h, P = 0.006; 2.2 ± 1.8 vs. 3.7 ± 2.4 at 24 h, P = 0.002). Fewer patients had interface displacements (32% vs. 56%; P = 0.01), oxygen desaturations (40% vs. 75%; P Conclusions Compared with the Venturi mask, NHF results in better oxygenation for the same set FiO2 after extubation. Use of NHF is associated with better comfort, fewer desaturations and interface displacements, and a lower reintubation rate. Clinical trial registered with www.clinicaltrials.gov (NCT 01575353).

Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial

Abstract: Background—Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results—This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfa...

Italy: Health System Review

Abstract: Italy is the sixth largest country in Europe and has the second highest average life expectancy, reaching 79.4 years for men and 84.5 years for women in 2011. There are marked regional differences for both men and women in most health indicators, reflecting the economic and social imbalance between the north and south of the country. The main diseases affecting the population are circulatory diseases, malignant tumours and respiratory diseases. Italy's health care system is a regionally based national health service that provides universal coverage largely free of charge at the point of delivery. The main source of financing is national and regional taxes, supplemented by copayments for pharmaceuticals and outpatient care. In 2012, total health expenditure accounted for 9.2 percent of GDP (slightly below the EU average of 9.6 percent). Public sources made up 78.2 percent of total health care spending. While the central government provides a stewardship role, setting the fundamental principles and goals of the health system and determining the core benefit package of health services available to all citizens, the regions are responsible for organizing and delivering primary, secondary and tertiary health care services as well as preventive and health promotion services. Faced with the current economic constraints of having to contain or even reduce health expenditure, the largest challenge facing the health system is to achieve budgetary goals without reducing the provision of health services to patients. This is related to the other key challenge of ensuring equity across regions, where gaps in service provision and health system performance persist. Other issues include ensuring the quality of professionals managing facilities, promoting group practice and other integrated care organizational models in primary care, and ensuring that the concentration of organizational control by regions of health-care providers does not stifle innovation.

Sarcopenia and Physical Frailty: Two Sides of the Same Coin

Abstract: Since the last decade, geriatrics and geron-tology researchers have been devoting anincreasing amount of efforts in the attemptof designing, developing, and implement-ing preventive interventions against con-ditions determining/driving the disablingcascade. The urgency of moving ahead inthe field is not merely dictated by scientificinterests; such need has indeed become afrequent and central item in the agendas ofpublic health authorities (Guralnik et al.,1996). In fact, there is a growing demandfor the identification of effective solutionsagainst the detrimental consequences thatage-related conditions (in particular, dis-abilities) exert on our healthcare systems.Specialattentionhasbeengiventosarcope-nia (Janssen et al., 2004) and frailty (Clegget al., 2013) because both are (1) highlyprevalent in the elderly, (2) associated withnegative health-related events, (3) poten-tially reversible, and (4) relatively easy toimplement in the clinical practice.The term “sarcopenia” was coined byRosenberg to indicate the loss of musclemass that accompanies aging. He clearlystated that “there is probably no decline instructureandfunctionmoredramaticthanthe decline in lean body mass or musclemass over the decades of life” (Rosenberg,1997). The muscle loss was therefore seenasameansof convenienceforexploringtheaging process and its consequences on anindividual’s health. Nevertheless, the skele-talmusclecannotbeisolatedbythehostingorganism. As such, it is still subject to theinfluence of all the positive and negativestressors to which the organism is exposed.In other words,the endogenous and exoge-nous phenomena capable of modifying theaging trajectory of the organism can also(more or less directly) influence the qualityand quantity of the muscle.Frailtyisthetermusedtoindicateageri-atric syndrome characterized by reducedhomeostatic reserves, which exposes theindividual at increased risk of negativehealth-related events (including falls, hos-pitalizations, worsening disability, institu-tionalization, and mortality) (Rodriguez-Manas et al., 2012; Clegg et al., 2013).Different operational definitions have beenproposed for capturing the frailty status,each one focusing on specific aspects of thesyndrome and detecting slightly differentrisk profiles (Theou et al., 2014). Never-theless, there is an overall agreement aboutthe key role that physical function (in par-ticular, mobility) plays in the determina-tion of the status of extreme vulnerability(Ferrucci et al., 2004; Daniels et al., 2008;Abellan van Kan et al., 2009).Since the beginning (roughly about 15–20years ago), sarcopenia and frailty havebeen studied in parallel. Being organ-specific, sarcopenia was more frequentlyobject of research in basic science, whereasthe concept of frailty tended to be moreeasily applied in the clinical setting (Bauerand Sieber, 2008). However, it was quiteinevitable that the two would have sooneror later started converging due to theirclose relationship with the aging process.Unfortunately, the definition of a clearframework within which sarcopenia andfrailty can be accommodated and stud-ied has yet to come. One major issue inthis context is the long-lasting, tiring, andpotentially pointless controversy about thecausal relationship existing between thetwo. Determining whether frailty is dueto sarcopenia, or sarcopenia is a clinicalmanifestation of frailty is consuming con-siderable efforts,and (from a very practicalviewpoint) rather resembles the problemof “the egg and the chicken.”We realize that the clarification of thispoint might have major consequences inthe field,determining different risk profilesto be detected and, consequently, redraw-ing outcomes as well as interventions to beadopted.Yet,theisolationof asinglepatho-physiological determinant responsible forthesecomplexconditions(aswellasforanyother age-related process) is quite unlikelyto be obtained, simply because aging isa complicated and still largely unknownphenomenon (Cesari et al., 2013).By stating this, we are not surrenderingto the current limitations of science. Weare instead soliciting the taking of morepragmatic decisions on this topic, waitingthat next-to-come scientific advancementsallow a better clarification and definitionof such urgent and pivotal matters. Fromthis perspective, deconstructing the innerfoundations of these“twin”conditions andtrying to focus on the shared and clinicalrelevant features of them might representa possible solution. By this way, we mighthave the opportunity to (1) define a uniquetarget for both sarcopenia and frailty, (2)simplify their operational definition, and(3)promotetheimplementationof thetwoconditions in both clinical and researchsettings.As shown in

Ataluren treatment of patients with nonsense mutation dystrophinopathy

Abstract: Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double-blind, placebo-controlled study; males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N = 57); ataluren 20, 20, 40 mg/kg (N = 60); or placebo (N = 57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the week 48 6MWD Δ = 31.3 meters, post hoc P = 0.056. Secondary endpoints (timed function tests) showed meaningful differences between ataluren 10, 10, 20 mg/kg, and placebo. Conclusions: As the first investigational new drug targeting the underlying cause of nm-dystrophinopathy, ataluren offers promise as a treatment for this orphan genetic disorder with high unmet medical need. Muscle Nerve 50: 477–487, 2014

Italian consensus for the classification and reporting of thyroid cytology

Abstract: IntroductionThyroid nodules are diagnosed with increasing frequencyin clinical practice. The first step in the management ofpatients presenting with thyroid nodules is an accuratetriage of those who should be referred to surgery [1–5]. Inspite of the advances in ultrasound (US) imaging [6–8] andthe promising results of molecular analysis [9–16], thisbasic step still strongly relies on cytology [3]. Among theacronyms used to indicate the sampling technique forthyroid cytology (FNA, FNAB, FNAC, FNC), fine-needleaspiration (FNA) is the most frequently adopted and it willbe employed in this document. When the cytologicspecimen is obtained without aspiration the term FNC(fine-needle cytology) may be used [2].In the recent years, a variety of four- to six-tieredreporting schemes for thyroid cytology have been proposedby different societies and institutions, with the aim ofimproving the communication between cytopathologistsand clinicians [17].With the aim to standardize the diagnostic terminologyin thyroid FNA, in 2007 the United States National CancerInstitute (NCI) has proposed a reporting system for thyroidcytology based on the NCI Thyroid FNA State-Of-ScienceConsensus Conference [18]. This system has gained widediffusion and the atlas ‘‘The Bethesda System for Report-ing Thyroid Cytology’’ (BSRTC) provided well-definedcriteria with exhaustive explanatory notes [19]. Followingthe recommendations of the 2009 European Federation ofCytology Societies (EFCS) symposium aiming at theworldwide unification of the reporting systems for thyroidcytology [20], a working group of the Royal College ofPathologists (RCPath) updated the reporting systemalready in use in UK since 2007 [21] using criteria that aresimilar to those used in BSRTC [22].In Italy, a 5-tiered classification, proposed in 2007 bythe Italian Society for Anatomic Pathology and Cytologyjoint with the Italian Division of the International Academyof Pathology (SIAPEC-IAP) [2], is currently used by mostinstitutions. In 2012 the Italian Societies of Endocrinology,i.e., the Italian Thyroid Association (AIT), the ItalianAssociation of Clinical Endocrinologists (AME), the Ital-ian Society of Endocrinology (SIE) and the SIAPEC-IAPappointed a working panel of experts to update the formerconsensus in line with the indications of the EFCS. Thepresent document provides a reporting scheme for thyroidcytology and the suggested clinical actions. This Consen-sus is not meant to address in detail all the morphological

Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.

Abstract: Objectives To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours. Design Observational diagnostic study using prospectively collected clinical and ultrasound data. Setting 24 ultrasound centres in 10 countries. Participants Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients. Main outcome measures Histological classification and surgical staging of the mass. Results The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate. Conclusions The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology.

Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial.

Abstract: Summary Background Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks. Methods We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC–IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m 2 ) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m 2 ) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842. Findings 822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2–30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2–20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8–20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80–1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3–4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen. Interpretation A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. Funding None.

Incorporation of Pazopanib in Maintenance Therapy of Ovarian Cancer

Abstract: Purpose Pazopanib is an oral, multikinase inhibitor of vascular endothelial growth factor receptor (VEGFR) -1/-2/-3, platelet-derived growth factor receptor (PDGFR) -α/-β, and c-Kit. Preclinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment. This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy. Patients and Methods Nine hundred forty patients with histologically confirmed cancer of the ovary, fallopian tube, or peritoneum, International Federation Gynecology Obstetrics (FIGO) stages II-IV, no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy were randomized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months. The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators. Results Maintenance pazopanib prolonged progression-fre...

Genetic PTX3 Deficiency and Aspergillosis in Stem-Cell Transplantation

Abstract: Background The soluble pattern-recognition receptor known as long pentraxin 3 (PTX3) has a nonredundant role in antifungal immunity. The contribution of single-nucleotide polymorphisms (SNPs) in PTX3 to the development of invasive aspergillosis is unknown. Methods We screened an initial cohort of 268 patients undergoing hematopoietic stem-cell transplantation (HSCT) and their donors for PTX3 SNPs modifying the risk of invasive aspergillosis. The analysis was also performed in a multicenter study involving 107 patients with invasive aspergillosis and 223 matched controls. The functional consequences of PTX3 SNPs were investigated in vitro and in lung specimens from transplant recipients. Results Receipt of a transplant from a donor with a homozygous haplotype (h2/h2) in PTX3 was associated with an increased risk of infection, in both the discovery study (cumulative incidence, 37% vs. 15%; adjusted hazard ratio, 3.08; P=0.003) and the confirmation study (adjusted odds ratio, 2.78; P=0.03), as well as with d...

Innovation, Employment and Skills in Advanced and Developing Countries: A Survey of Economic Literature

Abstract: I discuss the theoretical and empirical literature on the quantitative and qualitative employment impact of technological change. I also compare the relative explanatory power of competing economic theories, while detailing the macro, sectoral, and micro evidence on the issue with reference to advanced and developing economies. The main purpose of the paper is to offer a critical meta-analysis of both the theory and recent empirical achievements stemming from the relationship of technology and employment. More specifically, I draw some general conclusions about possible consequences of that relationship.

Cytogenetic Prognostication Within Medulloblastoma Subgroups

Abstract: Purpose Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication.