Showing papers by "Catholic University of the Sacred Heart published in 2019"
Istanbul University1, Heidelberg University2, University of Liège3, Karolinska University Hospital4, University of Southampton5, Catholic University of the Sacred Heart6, University of Toulouse7, Newcastle upon Tyne Hospitals NHS Foundation Trust8, University of Erlangen-Nuremberg9, First Faculty of Medicine, Charles University in Prague10, University of Antwerp11, Public Health Research Institute12, University of Verona13
TL;DR: An emphasis is placed on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarc Openia diagnosis, and provides clear cut-off points for measurements of variables that identify and characterise sarc openia.
Abstract: Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.
6,250 citations
University of California, Santa Barbara1, University of Texas at Austin2, University of Wrocław3, Dresden University of Technology4, University of Tartu5, Gulu University6, Middle East University7, Stockholm University8, University of the Punjab9, University of Nigeria, Nsukka10, Istanbul University11, Franklin & Marshall College12, Norwegian University of Science and Technology13, University of Algiers14, Australian National University15, Russian State University for the Humanities16, Russian Academy of Sciences17, İzmir University of Economics18, University of Social Sciences and Humanities19, Université catholique de Louvain20, Ankara University21, Pontifical Catholic University of Peru22, Cumhuriyet University23, University of the Republic24, ISCTE – University Institute of Lisbon25, The Chinese University of Hong Kong26, National Autonomous University of Mexico27, University of Pécs28, University of Constantine the Philosopher29, University of Maribor30, University of Zagreb31, University of Malaya32, Central University of Finance and Economics33, University of Crete34, University of Primorska35, Institute of Molecular and Cell Biology36, University of Amsterdam37, Catholic University of the Sacred Heart38, VU University Amsterdam39, University of Granada40, University of Delhi41, University of Havana42, Pontifical Catholic University of Rio de Janeiro43, University of Vienna44, Universiti Utara Malaysia45, Vilnius University46, University of British Columbia47, University of Sussex48, Romanian Academy49, Comenius University in Bratislava50, Slovak Academy of Sciences51, University of Monterrey52, SAS Institute53, DHA Suffa University54, Pontifical Catholic University of Chile55, South-West University "Neofit Rilski"56, University of São Paulo57, Kyung Hee University58, University of Ljubljana59
TL;DR: This work combines this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets and finds that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.
Abstract: Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.
1,827 citations
10 Jan 2019
TL;DR: This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases.
Abstract: Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
1,502 citations
TL;DR: An overview of the global impact and burden of frailty, the usefulness of the frailty concept in clinical practice, potential targets for frailty prevention, and directions that need to be explored in the future are provided.
1,075 citations
Carlos III Health Institute1, University of Cologne2, University of Sydney3, Paris Descartes University4, Pontifícia Universidade Católica do Rio Grande do Sul5, Universidade Federal de Ciências da Saúde de Porto Alegre6, University of California, San Diego7, Medical University of Graz8, University of Copenhagen9, Katholieke Universiteit Leuven10, University of Bologna11, University of the Witwatersrand12, RMIT University13, McGill University14, Hacettepe University15, University of Paris16, Utrecht University17, Mazandaran University of Medical Sciences18, Tel Aviv University19, Hospital General de México20, Istituto Giannina Gaslini21, Mahidol University22, Federal University of São Paulo23, King's College, Aberdeen24, Comenius University in Bratislava25, Boston Children's Hospital26, Complutense University of Madrid27, Hospital General Universitario Gregorio Marañón28, University Hospital Heidelberg29, University of California, Los Angeles30, American University of Beirut31, Innsbruck Medical University32, University of Lausanne33, Catholic University of Korea34, Goethe University Frankfurt35, National and Kapodistrian University of Athens36, Erasmus University Rotterdam37, Monash University38, Federal University of Rio de Janeiro39, Catholic University of the Sacred Heart40, University of Health Sciences Antigua41, National Institutes of Health42, Amrita Institute of Medical Sciences and Research Centre43, University of Pittsburgh44, University of Melbourne45, Peter MacCallum Cancer Centre46, P. D. Hinduja Hospital and Medical Research Centre47, University of Southern California48, Duke University49, Singapore General Hospital50, NewYork–Presbyterian Hospital51, Cardiff University52, University of Texas Health Science Center at San Antonio53, Children's Hospital of Philadelphia54, Post Graduate Institute of Medical Education and Research55
TL;DR: Management of mucormycosis depends on recognising disease patterns and on early diagnosis, and limited availability of contemporary treatments burdens patients in low and middle income settings.
Abstract: Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.
842 citations
University of Siena1, Boston Children's Hospital2, University of Florence3, University of Naples Federico II4, University of Brescia5, University of Messina6, University of Palermo7, University of Bari8, Seconda Università degli Studi di Napoli9, University of Padua10, Catholic University of the Sacred Heart11
TL;DR: In this article, the authors investigated the drug retention rate of interleukin (IL)-1 inhibitors on systemic JIA (sJIA) patients and evaluated predictive factors of drug survival based on data from a real-world setting concerning sJIA.
Abstract: Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA. Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers. Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002). Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.
615 citations
Heidelberg University1, Saint Louis University2, Maastricht University3, National Institutes of Health4, Baker IDI Heart and Diabetes Institute5, University of Alberta6, Duke University7, Charité8, Pennington Biomedical Research Center9, Mayo Clinic10, University of California, Irvine11, Catholic University of the Sacred Heart12, Agostino Gemelli University Polyclinic13, Sapienza University of Rome14, University of Pisa15, University of St. Gallen16
TL;DR: It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life‐long approach.
Abstract: The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.
346 citations
TL;DR: The most recent identified mechanisms underlying CAF-mediated control of tumor progression and therapy resistance, which include induction of the epithelial-to-mesenchymal transition (EMT), activation of survival pathways or stemness-related programs and metabolic reprogramming in tumor cells are dissected.
Abstract: In the last decades, the role of the microenvironment in tumor progression and therapeutic outcome has gained increasing attention. Cancer-associated fibroblasts (CAFs) have emerged as key players among stromal cells, owing to their abundance in most solid tumors and their diverse tumor-restraining/promoting roles. The interplay between tumor cells and neighboring CAFs takes place by both paracrine signals (cytokines, exosomes and metabolites) or by the multifaceted functions of the surrounding extracellular matrix. Here, we dissect the most recent identified mechanisms underlying CAF-mediated control of tumor progression and therapy resistance, which include induction of the epithelial-to-mesenchymal transition (EMT), activation of survival pathways or stemness-related programs and metabolic reprogramming in tumor cells. Importantly, the recently unveiled heterogeneity in CAFs claims tailored therapeutic efforts aimed at eradicating the specific subset facilitating tumor progression, therapy resistance and relapse. However, despite the large amount of pre-clinical data, much effort is still needed to translate CAF-directed anti-cancer strategies from the bench to the clinic.
314 citations
TL;DR: The present review aimed to focus on the impact of single food components, salt, food additives, and different dietary habits (i.e., vegan and vegetarian, gluten-free, ketogenic, high sugar, low FODMAP, Western-type, and Mediterranean diets) on gut microbiota composition in order to define the optimal diet for a healthy modulation of gut microbiota.
Abstract: The gut microbiota is a changing ecosystem, containing trillions of bacteria, continuously shaped by many factors, such as dietary habits, seasonality, lifestyle, stress, antibiotics use, or diseases. A healthy host–microorganisms balance must be respected in order to optimally maintain the intestinal barrier and immune system functions and, consequently, prevent disease development. In the past several decades, the adoption of modern dietary habits has become a growing health concern, as it is strongly associated with obesity and related metabolic diseases, promoting inflammation and both structural and behavioral changes in gut microbiota. In this context, novel dietary strategies are emerging to prevent diseases and maintain health. However, the consequences of these different diets on gut microbiota modulation are still largely unknown, and could potentially lead to alterations of gut microbiota, intestinal barrier, and the immune system. The present review aimed to focus on the impact of single food components (macronutrients and micronutrients), salt, food additives, and different dietary habits (i.e., vegan and vegetarian, gluten-free, ketogenic, high sugar, low FODMAP, Western-type, and Mediterranean diets) on gut microbiota composition in order to define the optimal diet for a healthy modulation of gut microbiota.
314 citations
University of Texas MD Anderson Cancer Center1, City of Hope National Medical Center2, University of Pennsylvania3, University of Kansas4, University of Nottingham5, German Cancer Research Center6, Paris Diderot University7, Vancouver General Hospital8, University of California, Davis9, University of Hong Kong10, Carlos III Health Institute11, University of Mainz12, Catholic University of the Sacred Heart13, Daiichi Sankyo14, Johns Hopkins University15
TL;DR: This trial aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy in the intention-to-treat population of patients with relapsed or refractory acute myeloid leukaemia.
Abstract: Summary Background Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy. Methods QuANTUM-R is a randomised, controlled, phase 3 trial done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG performance status 0–2 with relapsed or refractory (duration of first composite complete remission ≤6 months) FLT3-ITD acute myeloid leukaemia after standard therapy with or without allogeneic haemopoietic stem-cell transplantation were randomly assigned (2:1; permuted block size of 6; stratified by response to previous therapy and choice of chemotherapy via a phone-based and web-based interactive response system) to quizartinib (60 mg [30 mg lead-in] orally once daily) or investigator's choice of preselected chemotherapy: subcutaneous low-dose cytarabine (subcutaneous injection of cytarabine 20 mg twice daily on days 1–10 of 28-day cycles); intravenous infusions of mitoxantrone (8 mg/m2 per day), etoposide (100 mg/m2 per day), and cytarabine (1000 mg/m2 per day on days 1–5 of up to two 28-day cycles); or intravenous granulocyte colony-stimulating factor (300 μg/m2 per day or 5 μg/kg per day subcutaneously on days 1–5), fludarabine (intravenous infusion 30 mg/m2 per day on days 2–6), cytarabine (intravenous infusion 2000 mg/m2 per day on days 2–6), and idarubicin (intravenous infusion 10 mg/m2 per day on days 2–4 in up to two 28-day cycles). Patients proceeding to haemopoietic stem-cell transplantation after quizartinib could resume quizartinib after haemopoietic stem-cell transplantation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02039726, and follow-up is ongoing. Findings Between May 7, 2014, and Sept 13, 2017, 367 patients were enrolled, of whom 245 were randomly allocated to quizartinib and 122 to chemotherapy. Four patients in the quizartinib group and 28 in the chemotherapy group were not treated. Median follow-up was 23·5 months (IQR 15·4–32·3). Overall survival was longer for quizartinib than for chemotherapy (hazard ratio 0·76 [95% CI 0·58–0·98; p=0·02]). Median overall survival was 6·2 months (5·3–7·2) in the quizartinib group and 4·7 months (4·0–5·5) in the chemotherapy group. The most common non-haematological grade 3–5 treatment-emergent adverse events (within ≤30 days of last dose or >30 days if suspected to be a treatment-related event) for quizartinib (241 patients) and chemotherapy (94 patients) were sepsis or septic shock (46 patients [19%] for quizartinib vs 18 [19%] for chemotherapy), pneumonia (29 [12%] vs eight [9%]), and hypokalaemia (28 [12%] vs eight [9%]). The most frequent treatment-related serious adverse events were febrile neutropenia (18 patients [7%]), sepsis or septic shock (11 [5%]), QT prolongation (five [2%]), and nausea (five [2%]) in the quizartinib group, and febrile neutropenia (five [5%]), sepsis or septic shock (four [4%]), pneumonia (two [2%]), and pyrexia (two [2%]) in the chemotherapy group. Grade 3 QT prolongation in the quizartinib group was uncommon (eight [3%] by central reading, ten [4%] by investigator report); no grade 4 events occurred. There were 80 (33%) treatment-emergent deaths in the quizartinib group (31 [13%] of which were due to adverse events) and 16 (17%) in the chemotherapy group (nine [10%] of which were due to adverse events). Interpretation Treatment with quizartinib had a survival benefit versus salvage chemotherapy and had a manageable safety profile in patients with rapidly proliferative disease and very poor prognosis. Quizartinib could be considered a new standard of care. Given that there are only a few available treatment options, this study highlights the value of targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor. Funding Daiichi Sankyo.
285 citations
TL;DR: CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options.
Abstract: Background Ceftazidime-avibactam (CAZ-AVI) has been approved in Europe for the treatment of complicated intra-abdominal and urinary tract infections, as well as hospital-acquired pneumonia, and for gram-negative infections with limited treatment options. CAZ-AVI displays in vitro activity against Klebsiella pneumoniae carbapenemase (KPC) enzyme producers, but clinical trial data on its efficacy in this setting are lacking. Methods We retrospectively reviewed 138 cases of infections caused by KPC-producing K. pneumoniae (KPC-Kp) in adults who received CAZ-AVI in compassionate-use programs in Italy. Case features and outcomes were analyzed, and survival was then specifically explored in the large subcohort whose infections were bacteremic. Results The 138 patients started CAZ-AVI salvage therapy after a first-line treatment (median, 7 days) with other antimicrobials. CAZ-AVI was administered with at least 1 other active antibiotic in 109 (78.9%) cases. Thirty days after infection onset, 47 (34.1%) of the 138 patients had died. Thirty-day mortality among the 104 patients with bacteremic KPC-Kp infections was significantly lower than that of a matched cohort whose KPC-Kp bacteremia had been treated with drugs other than CAZ-AVI (36.5% vs 55.8%, P = .005). Multivariate analysis of the 208 cases of KPC-Kp bacteremia identified septic shock, neutropenia, Charlson comorbidity index ≥3, and recent mechanical ventilation as independent predictors of mortality, whereas receipt of CAZ-AVI was the sole independent predictor of survival. Conclusions CAZ-AVI appears to be a promising drug for treatment of severe KPC-Kp infections, especially those involving bacteremia.
TL;DR: This is the first prospective demonstration that a rechallenge strategy with cetuximab and irinotecan may be active in patients with RAS and BRAF wild-type mCRC with acquired resistance to first-line irinOTecan- and cetUXimab-based therapy.
Abstract: Importance Based on a small retrospective study, rechallenge with cetuximab-based therapy for patients withKRASwild-type metastatic colorectal cancer (mCRC) who were previously treated with the same anti–epidermal growth factor receptor–based regimen might be efficacious. Recent data suggest the role of liquid biopsy as a tool to track molecular events in circulating tumor DNA (ctDNA). Objective To prospectively assess the activity of cetuximab plus irinotecan as third-line treatment for patients withRASandBRAFwild-type mCRC who were initially sensitive to and then resistant to first-line irinotecan- and cetuximab-based therapy. Design, Setting, and Participants Multicenter phase 2 single-arm trial conducted from January 7, 2015, to June 19, 2017. Liquid biopsies for analysis of ctDNA were collected at baseline. Main eligibility criteria includedRASandBRAFwild-type status on tissue samples; prior first-line irinotecan- and cetuximab-based regimen with at least partial response, progression-free survival of at least 6 months with first-line therapy, and progression within 4 weeks after last dose of cetuximab; and prior second-line oxaliplatin- and bevacizumab-based treatment. Interventions Biweekly cetuximab, 500 mg/m2, plus irinotecan, 180 mg/m2. Main Outcomes and Measures Overall response rate according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included progression-free survival and overall survival and, as an exploratory analysis,RASmutations in ctDNA. Results Twenty-eight patients (9 women and 19 men; median age, 69 years [range, 45-79 years]) were enrolled. Six partial responses (4 confirmed) and 9 disease stabilizations were reported (response rate, 21%; 95% CI, 10%-40%; disease control rate, 54%; 95% CI, 36%-70%). Primary end point was met because lower limit of 95% CI of response rate was higher than 5%.RASmutations were found in ctDNA collected at rechallenge baseline in 12 of 25 evaluable patients (48%). NoRASmutations were detected in samples from patients who achieved confirmed partial response. Patients withRASwild-type ctDNA had significantly longer progression-free survival than those withRASmutated ctDNA (median progression-free survival, 4.0 vs 1.9 months; hazard ratio, 0.44; 95% CI, 0.18-0.98;P = .03). Conclusions and Relevance This is the first prospective demonstration that a rechallenge strategy with cetuximab and irinotecan may be active in patients withRASandBRAFwild-type mCRC with acquired resistance to first-line irinotecan- and cetuximab-based therapy. The evaluation ofRASmutational status on ctDNA might be helpful in selecting candidate patients. Trial Registration ClinicalTrials.gov Identifier:NCT02296203
University of Liège1, University of Toulouse2, Heidelberg University3, University of Erlangen-Nuremberg4, University of Southampton5, University of Oxford6, King Saud University7, World Health Organization8, Vrije Universiteit Brussel9, Catholic University of the Sacred Heart10, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico11, University of Milan12, Tufts University13, Australian Catholic University14, University of Sheffield15, Ghent University Hospital16, Medical University of Graz17, Public Health Research Institute18, Geneva College19
TL;DR: An overview of different methods available and applicable in clinical settings and the use of grip strength to measure muscle strength and theUse of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice are proposed.
Abstract: It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).
TL;DR: The mechanisms that underlie superficial erosion, a cause of coronary thrombosis distinct from plaque rupture, have garnered recent interest as mentioned in this paper, and a substantial shift in the mechanisms of the complications of atherosclerosis has been proposed.
Abstract: The mechanisms that underlie superficial erosion, a cause of coronary thrombosis distinct from plaque rupture, have garnered recent interest. In an era of improved control of traditional risk factors, such as LDL (low-density lipoprotein), plaque erosion may assume greater clinical importance. Plaques complicated by erosion tend to be matrix-rich, lipid-poor, and usually lack prominent macrophage collections, unlike plaques that rupture, which characteristically have thin fibrous caps, large lipid pools, and abundant foam cells. Thrombi that complicate superficial erosion seem more platelet-rich than the fibrinous clots precipitated by plaque rupture. The pathogenesis of plaque rupture probably does not pertain to superficial erosion, a process heretofore little understood mechanistically. We review here data that support a substantial shift in the mechanisms of the thrombotic complications of atherosclerosis. We further consider pathophysiologic processes recently implicated in the mechanisms of erosion. Multiple processes likely predispose plaques to superficial erosion, including experiencing disturbed flow, basement membrane breakdown, endothelial cell death, and detachment potentiated by innate immune activation mediated through pattern-recognition receptors and endothelial-to-mesenchymal transition. Monocytes/macrophages predominate in the pathogenesis of plaque rupture and consequent thrombosis, but polymorphonuclear leukocytes likely promote endothelial damage during superficial erosion. The formation of neutrophil extracellular traps probably perpetuates and propagates intimal injury and potentiates thrombosis due to superficial erosion. These considerations have profound clinical implications. Acute coronary syndromes because of erosion may not require immediate invasive therapy. Understanding the biological bases of erosion points to novel therapies for acute coronary syndrome caused by erosion. Future research should probe further the mechanisms of superficial erosion, and develop point-of-care tests to distinguish acute coronary syndromes provoked by erosion versus rupture that may direct more precision management. Future clinical investigations should evaluate intervening on the targets that have emerged from experimental studies and the management strategies that they inform.
TL;DR: Treatment with POEM compared with pneumatic dilation resulted in a significantly higher treatment success rate at 2 years, and these findings support consideration of POEM as an initial treatment option for patients with achalasia.
Abstract: Importance Case series suggest favorable results of peroral endoscopic myotomy (POEM) for treatment of patients with achalasia Data comparing POEM with pneumatic dilation, the standard treatment for patients with achalasia, are lacking Objective To compare the effects of POEM vs pneumatic dilation as initial treatment of treatment-naive patients with achalasia Design, Setting, and Participants This randomized multicenter clinical trial was conducted at 6 hospitals in the Netherlands, Germany, Italy, Hong Kong, and the United States Adult patients with newly diagnosed achalasia and an Eckardt score greater than 3 who had not undergone previous treatment were included The study was conducted between September 2012 and July 2015, the duration of follow-up was 2 years after the initial treatment, and the final date of follow-up was November 22, 2017 Interventions Randomization to receive POEM (n = 67) or pneumatic dilation with a 30-mm and a 35-mm balloon (n = 66), with stratification according to hospital Main Outcomes and Measures The primary outcome was treatment success (defined as an Eckardt score ≤3 and the absence of severe complications or re-treatment) at the 2-year follow-up A total of 14 secondary end points were examined among patients without treatment failure, including integrated relaxation pressure of the lower esophageal sphincter via high-resolution manometry, barium column height on timed barium esophagogram, and presence of reflux esophagitis Results Of the 133 randomized patients, 130 (mean age, 486 years; 73 [56%] men) underwent treatment (64 in the POEM group and 66 in the pneumatic dilation group) and 126 (95%) completed the study The primary outcome of treatment success occurred in 58 of 63 patients (92%) in the POEM group vs 34 of 63 (54%) in the pneumatic dilation group, a difference of 38% ([95% CI, 22%-52%];P Conclusions and Relevance Among treatment-naive patients with achalasia, treatment with POEM compared with pneumatic dilation resulted in a significantly higher treatment success rate at 2 years These findings support consideration of POEM as an initial treatment option for patients with achalasia Trial Registration Netherlands Trial Register number:NTR3593
TL;DR: The focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites, considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach.
Abstract: Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites. MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.
TL;DR: The genetic epigenetic theory is compatible with all observations on endometriosis and a polygenetic/polyepigenetic mechanism is proposed to explain the hereditary aspects, the predisposition, and the endometiosis-associated changes in theendometrium, immunology, and placentation.
Université libre de Bruxelles1, Catholic University of the Sacred Heart2, Agostino Gemelli University Polyclinic3, University of Paris-Sud4, Nottingham University Hospitals NHS Trust5, Erasmus University Medical Center6, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico7, University of Amsterdam8
TL;DR: Endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas is suggested.
Abstract: ESGE suggests endoscopic therapy and/or extracorporeal shockwave lithotripsy (ESWL) as the first-line therapy for painful uncomplicated chronic pancreatitis (CP) with an obstructed main pancreatic duct (MPD) in the head/body of the pancreas. The clinical response should be evaluated at 6 – 8 weeks; if it appears unsatisfactory, the patient’s case should be discussed again in a multidisciplinary team and surgical options should be considered. Weak recommendation, low quality evidence. ESGE suggests, for the selection of patients for initial or continued endoscopic therapy and/or ESWL, taking into consideration predictive factors associated with a good long-term outcome. These include, at initial work-up, absence of MPD stricture, a short disease duration, non-severe pain, absence or cessation of cigarette smoking and of alcohol intake, and, after initial treatment, complete removal of obstructive pancreatic stones and resolution of pancreatic duct stricture with stenting. Weak recommendation, low quality evidence. ESGE recommends ESWL for the clearance of radiopaque obstructive MPD stones larger than 5 mm located in the head/body of the pancreas and endoscopic retrograde cholangiopancreatography (ERCP) for MPD stones that are radiolucent or smaller than 5 mm. Strong recommendation, moderate quality evidence. ESGE suggests restricting the use of endoscopic therapy after ESWL to patients with no spontaneous clearance of pancreatic stones after adequate fragmentation by ESWL. Weak recommendation, moderate quality evidence. ESGE suggests treating painful dominant MPD strictures with a single 10-Fr plastic stent for one uninterrupted year if symptoms improve after initial successful MPD drainage. The stent should be exchanged if necessary, based on symptoms or signs of stent dysfunction at regular pancreas imaging at least every 6 months. ESGE suggests consideration of surgery or multiple side-by-side plastic stents for symptomatic MPD strictures persisting beyond 1 year after the initial single plastic stenting, following multidisciplinary discussion. Weak recommendation, low quality evidence. ESGE recommends endoscopic drainage over percutaneous or surgical treatment for uncomplicated chronic pancreatitis (CP)-related pseudocysts that are within endoscopic reach. Strong recommendation, moderate quality evidence. ESGE recommends retrieval of transmural plastic stents at least 6 weeks after pancreatic pseudocyst regression if MPD disruption has been excluded, and long-term indwelling of transmural double-pigtail plastic stents in patients with disconnected pancreatic duct syndrome. Strong recommendation, low quality evidence. ESGE suggests the temporary insertion of multiple side-by-side plastic stents or of a fully covered self-expandable metal stent (FCSEMS) for treating CP-related benign biliary strictures. Weak recommendation, moderate quality evidence. ESGE recommends maintaining a registry of patients with biliary stents and recalling them for stent removal or exchange. Strong recommendation, low quality evidence.
TL;DR: The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events.
Abstract: Aims The CLIMA study, on the relationship between coronary plaque morphology of the left anterior descending artery and twelve months clinical outcome, was designed to explore the predictive value of multiple high-risk plaque features in the same coronary lesion [minimum lumen area (MLA), fibrous cap thickness (FCT), lipid arc circumferential extension, and presence of optical coherence tomography (OCT)-defined macrophages] as detected by OCT. Composite of cardiac death and target segment myocardial infarction was the primary clinical endpoint.Methods and results From January 2013 to December 2016, 1003 patients undergoing OCT evaluation of the untreated proximal left am :sults anterior descending coronary artery in the context of clinically indicated coronary angiogram were prospectively enrolled at 11 independent centres (clinicattriaLgov identifier NCT02883088). At 1-year, the primary clinical endpoint was observed in 37 patients (3.7%). In a total of 1776 lipid plaques, presence of MLA 180' (HR 2.4, 95% CI 1.2-4.8), and OCT-defined macrophages (HR 2.7, 95% CI 1.2-6.1) were all associated with increased risk of the primary endpoint. The pre-specified combination of plaque features (simultaneous presence of the four OCT criteria in the same plaque) was observed in 18.9% of patients experiencing the primary endpoint and was an independent predictor of events (HR 7.54, 95% CI 3.1-18.6).Conclusion The simultaneous presence of four high-risk OCT plaque features was found to be associated with a higher risk of major coronary events.
TL;DR: The aim of this narrative review was to determine the magnitude of interaction between the Mediterranean diet and more widespread types of cancer so as to give a first and useful overview on this relationship identifying, with a nutritional approach, those nutrients of Mediterranean diet able to reduce cancer incidence.
Abstract: The Mediterranean diet is considered one of the most worldwide healthy dietary patterns thanks to a combination of foods rich mainly in antioxidants and anti-inflammatory nutrients. Many studies have demonstrated a strong and inverse relationship between a high level of Mediterranean diet adherence and some chronic diseases (such as cardiovascular diseases, diabetes, etc.) and cancer. Given its protective effects in reducing oxidative and inflammatory processes of cells and avoiding DNA damages, cell proliferation, and their survival, angiogenesis, inflammations and metastasis, the Mediterranean diet is considered a powerful and manageable method to fight cancer incidence. The aim of this narrative review was to determine the magnitude of interaction between the Mediterranean diet and more widespread types of cancer so as to give a first and useful overview on this relationship identifying, with a nutritional approach, those nutrients of Mediterranean diet able to reduce cancer incidence.
TL;DR: This study found that the addition of SIRT with 90yttrium-loaded resin microspheres to sorafenib treatment in people with advanced HCC did not significantly improve overall survival compared with sorafinib treatment alone, however, the results suggest how future studies on this combination therapy in patients withadvanced HCC could be designed.
TL;DR: In the treatment of ROP, ranibizumab 0·2 mg might be superior to laser therapy, with fewer unfavourable ocular outcomes than laser therapy and with an acceptable 24-week safety profile.
TL;DR: The perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin is opened.
Abstract: S100B is a Ca2+ -binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage-Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia-1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over-expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.
TL;DR: The different modalities to quantify exercise intolerance, the pathophysiology of HF, and comorbid conditions as they lead to reductions in exercise and functional capacity are reviewed, highlighting the fact that distinct causes may coexist and variably contribute to exercise intolerance in patients with HF.
20 Feb 2019
TL;DR: This study shows that sensory substitution based on intraneural stimulation can deliver position feedback in real time and in conjunction with somatotopic tactile feedback, and paves a way to more sophisticated bidirectional bionic limbs conveying richer, multimodal sensations.
Abstract: Current myoelectric prostheses allow transradial amputees to regain voluntary motor control of their artificial limb by exploiting residual muscle function in the forearm. However, the overreliance on visual cues resulting from a lack of sensory feedback is a common complaint. Recently, several groups have provided tactile feedback in upper limb amputees using implanted electrodes, surface nerve stimulation, or sensory substitution. These approaches have led to improved function and prosthesis embodiment. Nevertheless, the provided information remains limited to a subset of the rich sensory cues available to healthy individuals. More specifically, proprioception, the sense of limb position and movement, is predominantly absent from current systems. Here, we show that sensory substitution based on intraneural stimulation can deliver position feedback in real time and in conjunction with somatotopic tactile feedback. This approach allowed two transradial amputees to regain high and close-to-natural remapped proprioceptive acuity, with a median joint angle reproduction precision of 9.1° and a median threshold to detection of passive movements of 9.5°, which was comparable with results obtained in healthy participants. The simultaneous delivery of position information and somatotopic tactile feedback allowed both amputees to discriminate the size and compliance of four objects with high levels of performance (75.5%). These results demonstrate that tactile information delivered via somatotopic neural stimulation and position information delivered via sensory substitution can be exploited simultaneously and efficiently by transradial amputees. This study paves a way to more sophisticated bidirectional bionic limbs conveying richer, multimodal sensations.
TL;DR: Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age‐related health deterioration; this review provides an overview of knowledge gaps and future directions.
Abstract: This review discusses the interplay between multimorbidity (i.e. co-occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians' fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug-drug and drug-disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age-related health deterioration; this review provides an overview of knowledge gaps and future directions.
TL;DR: The main evidence on the use of sourdough fermentation for salt reduction in baked goods, management of irritable bowel syndrome (IBS), synthesis/release of bioactive compounds, and exploitation of the potential of non-conventional flours and milling by-products are reported.
TL;DR: This systematic review confirms that both OLP and OLL, the latter with a slightly higher TR, may be considered potentially malignant disorders and suggest that erosive type, female gender and tongue site should be considered as risk factors for OLP transformation.
Abstract: Objective The aim of this study was to systematically review the literature to determine: (a) the malignant transformation rate (TR) of oral lichen planus (OLP) and its risk factors; (b) whether or not oral lichenoid lesions (OLL) have a different malignant TR. Materials and methods PubMed, Scopus, and Web of Science were used as search engines: only observational, full-length, English language studies were investigated. PRISMA protocol was used to evaluate and present results. PROSPERO registration code is CRD42016048529. Results Among 7,429 records screened, only 21 were included in this review. Ninety-two of 6,559 patients developed oral squamous cell carcinoma, with an overall TR of 1.40% (1.37% for OLP and 2.43% for OLL), an annual TR of 0.20%. Female gender, red clinical forms, and tongue site seem to slightly increase the transformation risk. Conclusions This systematic review confirms that both OLP and OLL, the latter with a slightly higher TR, may be considered potentially malignant disorders and suggest that erosive type, female gender and tongue site should be considered as risk factors for OLP transformation. Major efforts should be done to establish strict clinical and histological criteria to diagnose OLP and to perform sounder methodological observational studies.
TL;DR: The heritable core microbes, therefore, present primary targets for rumen manipulation toward sustainable and environmentally friendly agriculture.
Abstract: A 1000-cow study across four European countries was undertaken to understand to what extent ruminant microbiomes can be controlled by the host animal and to identify characteristics of the host rumen microbiome axis that determine productivity and methane emissions. A core rumen microbiome, phylogenetically linked and with a preserved hierarchical structure, was identified. A 39-member subset of the core formed hubs in co-occurrence networks linking microbiome structure to host genetics and phenotype (methane emissions, rumen and blood metabolites, and milk production efficiency). These phenotypes can be predicted from the core microbiome using machine learning algorithms. The heritable core microbes, therefore, present primary targets for rumen manipulation toward sustainable and environmentally friendly agriculture.
TL;DR: The landscape of therapeutic developments in paediatric NAFLD is expanding, bringing the identification of safe and effective treatments closer and the development of drugs that can modify liver steatosis, inflammation and fibrosis is expanding.
Abstract: Nonalcoholic fatty liver disease (NAFLD) has rapidly become the most common form of chronic liver disease in children and adolescents. Over the past 5 years, developments have revolutionized our understanding of the genetic factors, natural history, diagnostic modalities and therapeutic targets for this disease. New polymorphisms, such as those in PNPLA3, TM6SF2, MBOAT7 and GCKR, have been identified and used to predict the development and severity of NAFLD in both adults and children, and their interaction with environmental factors has been elucidated. Studies have demonstrated the true burden of paediatric NAFLD and its progression to end-stage liver disease in adulthood. In particular, nonalcoholic steatohepatitis can progress to advanced fibrosis and cirrhosis, emphasizing the importance of early diagnosis. Non-invasive imaging tests, such as transient elastography, will probably replace liver biopsy for the diagnosis of nonalcoholic steatohepatitis and the assessment of fibrosis severity in the near future. The therapeutic landscape is also expanding rapidly with the development of drugs that can modify liver steatosis, inflammation and fibrosis, indicating that pharmacotherapy for NAFLD will become available in the future. In this Review, we summarize current knowledge and new advances related to the pathogenesis and management of paediatric NAFLD.