Showing papers by "Rambam Health Care Campus published in 2017"
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TL;DR: The InTBIR Participants and Investigators have provided informed consent for the study to take place in Poland.
Abstract: Additional co-authors: Endre Czeiter, Marek Czosnyka, Ramon Diaz-Arrastia, Jens P Dreier, Ann-Christine Duhaime, Ari Ercole, Thomas A van Essen, Valery L Feigin, Guoyi Gao, Joseph Giacino, Laura E Gonzalez-Lara, Russell L Gruen, Deepak Gupta, Jed A Hartings, Sean Hill, Ji-yao Jiang, Naomi Ketharanathan, Erwin J O Kompanje, Linda Lanyon, Steven Laureys, Fiona Lecky, Harvey Levin, Hester F Lingsma, Marc Maegele, Marek Majdan, Geoffrey Manley, Jill Marsteller, Luciana Mascia, Charles McFadyen, Stefania Mondello, Virginia Newcombe, Aarno Palotie, Paul M Parizel, Wilco Peul, James Piercy, Suzanne Polinder, Louis Puybasset, Todd E Rasmussen, Rolf Rossaint, Peter Smielewski, Jeannette Soderberg, Simon J Stanworth, Murray B Stein, Nicole von Steinbuchel, William Stewart, Ewout W Steyerberg, Nino Stocchetti, Anneliese Synnot, Braden Te Ao, Olli Tenovuo, Alice Theadom, Dick Tibboel, Walter Videtta, Kevin K W Wang, W Huw Williams, Kristine Yaffe for the InTBIR Participants and Investigators
1,354 citations
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University of Belgrade1, Danube University Krems2, Max Planck Society3, University of Glasgow4, Vestre Viken Hospital Trust5, University Hospital Bonn6, Shaare Zedek Medical Center7, Radboud University Nijmegen8, Jewish General Hospital9, Pusan National University10, Samsung Medical Center11, Inha University12, Hallym University13, Gachon University14, University of Tuzla15, University of Michigan16, Technion – Israel Institute of Technology17, Rambam Health Care Campus18, University of Edinburgh19, university of lille20, Tel Aviv University21
TL;DR: PSD is proposed as a label for any dementia following stroke in temporal relation and no specific biomarkers have been proven to robustly discriminate vulnerable patients (‘at risk brains’) from those with better prognosis or to discriminate Alzheimer’s disease dementia from PSD.
Abstract: Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients (‘at risk brains’) from those with better prognosis or to discriminate Alzheimer’s disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing.
359 citations
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TL;DR: This review will address the concepts of AMI with the aim of focusing on specific areas where early diagnosis and management hold the strongest potential for improving outcomes in this disease process.
Abstract: Acute mesenteric ischemia (AMI) is typically defined as a group of diseases characterized by an interruption of the blood supply to varying portions of the small intestine, leading to ischemia and secondary inflammatory changes. If untreated, this process will eventuate in life threatening intestinal necrosis. The incidence is low, estimated at 0.09–0.2% of all acute surgical admissions. Therefore, although the entity is an uncommon cause of abdominal pain, diligence is always required because if untreated, mortality has consistently been reported in the range of 50%. Early diagnosis and timely surgical intervention are the cornerstones of modern treatment and are essential to reduce the high mortality associated with this entity. The advent of endovascular approaches in parallel with modern imaging techniques may provide new options. Thus, we believe that a current position paper from World Society of Emergency Surgery (WSES) is warranted, in order to put forth the most recent and practical recommendations for diagnosis and treatment of AMI. This review will address the concepts of AMI with the aim of focusing on specific areas where early diagnosis and management hold the strongest potential for improving outcomes in this disease process. Some of the key points include the prompt use of CT angiography to establish the diagnosis, evaluation of the potential for revascularization to re-establish blood flow to ischemic bowel, resection of necrotic intestine, and use of damage control techniques when appropriate to allow for re-assessment of bowel viability prior to definitive anastomosis and abdominal closure.
327 citations
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Marche Polytechnic University1, United Arab Emirates University2, Obafemi Awolowo University3, John Hunter Hospital4, Rambam Health Care Campus5, University of Hawaii at Manoa6, University of Santiago de Compostela7, University of California, San Diego8, Tbilisi State Medical University9, University of Maryland, Baltimore10, Russian National Research Medical University11, Virginia Commonwealth University12, State University of Campinas13, Mansoura University14, Yonsei University15, Ruhr University Bochum16, Inje University17, University of Southern California18, Erzincan University19, University of Belgrade20, Tel Aviv University21, Foothills Medical Centre22, Kyoto University23, Edendale Hospital24, University of Helsinki25, Universidad Nacional de Asunción26, University of Washington27, Pt. B.D. Sharma PGIMS Rohtak28, University of the West Indies29, University of Colorado Denver30, University of Ilorin31, Jordan University of Science and Technology32, University of Valle33, University of São Paulo34, Ehime University35, Tan Tock Seng Hospital36, Stavanger University Hospital37, University of Bergen38, Charles University in Prague39, Radboud University Nijmegen40, Harvard University41, Chang Gung University42, Sher-I-Kashmir Institute of Medical Sciences43, Royal Perth Hospital44
TL;DR: The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.
Abstract: Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide. The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important. In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs. The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.
289 citations
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University of Colorado Denver1, The Queen's Medical Center2, Örebro University3, Rambam Health Care Campus4, University of Pittsburgh5, Virginia Commonwealth University6, UC San Diego Health System7, State University of Campinas8, St. Michael's Hospital9, Foothills Medical Centre10, University of Grenoble11, Harvard University12, John Hunter Hospital13, University of KwaZulu-Natal14, Royal Perth Hospital15, United Arab Emirates University16
TL;DR: The World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines are presented.
Abstract: Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be ultimately based on the physiology of the patient and the anatomy of the injury. This paper presents the World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines.
260 citations
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Rambam Health Care Campus1, The Queen's Medical Center2, Denver Health Medical Center3, Military Academy4, Hadassah Medical Center5, Goethe University Frankfurt6, Harvard University7, Virginia Commonwealth University8, Stavanger University Hospital9, Örebro University10, Radboud University Nijmegen11, State University of Campinas12, LAC+USC Medical Center13, Tel Aviv University14, University of Western Ontario15, Foothills Medical Centre16, United Arab Emirates University17, Universidade Federal de Juiz de Fora18, University of KwaZulu-Natal19, University of Grenoble20, University of Michigan21, University of Helsinki22, Stanford University23, Yale University24, Westchester Medical Center25, Tokyo Medical and Dental University26, UC San Diego Health System27, University of Washington28, University of Toronto29, University of California, Davis30, University of Buea31, Royal Perth Hospital32, University of Pittsburgh33
TL;DR: The World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines are presented to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management.
Abstract: Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.
218 citations
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TL;DR: Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, and treatment discontinuation.
Abstract: Background Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. Methods PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. Results A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. Conclusion PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer.
206 citations
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TL;DR: In vitro and in vivo effects of Moses technology in Holmium laser resulted in more efficient laser lithotripsy, in addition to significantly reduced stone retropulsion, and displayed a margin of safety that may result in a shorter procedural time and safer lithotRIpsy.
Abstract: Objective: To evaluate in vitro and in vivo effects of Moses technology in Holmium laser and to compare it with the Regular mode in terms of lithotripsy efficiency and laser-tissue interactions. Methods: The Lumenis® Pulse™ P120H holmium laser system together with Moses D/F/L fibers were used to compare the Regular mode with the Moses modes in stone retropulsion by using a high-speed camera, and stone ablation efficiency. In addition, a porcine ureteroscopy model was used to assess stone fragmentation and dusting as well as laser-tissue interaction with the ureteral wall. Results: After a laser pulse, in vitro stone displacement experiments showed a significant reduction in retropulsion when using the Moses mode. The stone movement was reduced by 50 times at 0.8 J and 10 Hz (p < 0.01). The pronounced reduction of retropulsion in the Moses mode was clearly observed during fragmentation setting (high energy) and dusting (low energy, high Hz). In addition, stone fragmentation tests showed that the M...
159 citations
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Harvard University1, Paris Descartes University2, French Institute of Health and Medical Research3, Université Paris-Saclay4, University of Paris5, Autonomous University of Barcelona6, McGill University7, Massachusetts Institute of Technology8, Ghent University9, University of Freiburg10, Yonsei University11, University of Erlangen-Nuremberg12, University of Münster13, Max Planck Society14, National Institutes of Health15, Iran University of Medical Sciences16, King Edward Memorial Hospital17, GeneDx18, Hospital Kuala Lumpur19, Mackay Memorial Hospital20, Boston Children's Hospital21, Oklahoma Medical Research Foundation22, University of Michigan23, King Abdulaziz University24, Université de Montréal25, Baylor College of Medicine26, University of Jordan27, University of Tehran28, Yamagata University29, Hacettepe University30, University of Western Ontario31, University of Groningen32, Guy's and St Thomas' NHS Foundation Trust33, Cairo University34, Taipei Medical University35, University of Duisburg-Essen36, University of Utah37, Mahidol University38, University of Oklahoma39, University of Texas Southwestern Medical Center40, Tuen Mun Hospital41, Singapore–MIT alliance42, Yale University43, Rockefeller University44, University of Toronto45, Rambam Health Care Campus46
TL;DR: Four new monogenic causes of GAMOS are identified, a link between KEOPS function and human disease is described, and potential pathogenic mechanisms are delineated.
Abstract: Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.
149 citations
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TL;DR: Although the health-care system itself is very well integrated in relation to the country's two main ethnic groups, it is thought that health in its widest sense might help provide a bridge to peace and reconciliation between the country and its neighbours.
128 citations
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TL;DR: This external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source.
Abstract: Summary Background A physician is frequently unable to distinguish bacterial from viral infections. ImmunoXpert is a novel assay combining three proteins: tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma induced protein-10 (IP-10), and C-reactive protein (CRP). We aimed to externally validate the diagnostic accuracy of this assay in differentiating between bacterial and viral infections and to compare this test with commonly used biomarkers. Methods In this prospective, double-blind, international, multicentre study, we recruited children aged 2–60 months with lower respiratory tract infection or clinical presentation of fever without source at four hospitals in the Netherlands and two hospitals in Israel. A panel of three experienced paediatricians adjudicated a reference standard diagnosis for all patients (ie, bacterial or viral infection) using all available clinical and laboratory information, including a 28-day follow-up assessment. The panel was masked to the assay results. We identified majority diagnosis when two of three panel members agreed on a diagnosis and unanimous diagnosis when all three panel members agreed on the diagnosis. We calculated the diagnostic performance (ie, sensitivity, specificity, positive predictive value, and negative predictive value) of the index test in differentiating between bacterial (index test positive) and viral (index test negative) infection by comparing the test classification with the reference standard outcome. Findings Between Oct 16, 2013 and March 1, 2015, we recruited 777 children, of whom 577 (mean age 21 months, 56% male) were assessed. The majority of the panel diagnosed 71 cases as bacterial infections and 435 as viral infections. In another 71 patients there was an inconclusive panel diagnosis. The assay distinguished bacterial from viral infections with a sensitivity of 86·7% (95% CI 75·8–93·1), a specificity of 91·1% (87·9–93·6), a positive predictive value of 60·5% (49·9–70·1), and a negative predictive value of 97·8% (95·6–98·9). In the more clear cases with unanimous panel diagnosis (n=354), sensitivity was 87·8% (74·5–94·7), specificity 93·0% (89·6–95·3), positive predictive value 62·1% (49·2–73·4), and negative predictive value 98·3% (96·1–99·3). Interpretation This external validation study shows the diagnostic value of a three-host protein-based assay to differentiate between bacterial and viral infections in children with lower respiratory tract infection or fever without source. This diagnostic based on CRP, TRAIL, and IP-10 has the potential to reduce antibiotic misuse in young children. Funding MeMed Diagnostics.
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TL;DR: A rapid antibiotic susceptibility test and automated data analysis algorithm that can, unlike traditional methods, deliver results on the same working day in an efficient and translatable manner for clinical use and an algorithm for automated dataAnalysis and a multiplexing system promoting practicality and translatability for clinical settings are introduced.
Abstract: Antibiotic resistance is a major global health concern that requires action across all sectors of society. In particular, to allow conservative and effective use of antibiotics clinical settings require better diagnostic tools that provide rapid determination of antimicrobial susceptibility. We present a method for rapid and scalable antimicrobial susceptibility testing using stationary nanoliter droplet arrays that is capable of delivering results in approximately half the time of conventional methods, allowing its results to be used the same working day. In addition, we present an algorithm for automated data analysis and a multiplexing system promoting practicality and translatability for clinical settings. We test the efficacy of our approach on numerous clinical isolates and demonstrate a 2-d reduction in diagnostic time when testing bacteria isolated directly from urine samples.
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TL;DR: Dietary treatment combining PEN with the Crohn's Disease Exclusion Diet may be a useful salvage regimen for patients failing biological therapy despite dose escalation.
Abstract: Background: Loss of response (LoR) to biologics in Crohn's disease (CD) is a significant clinical problem. Dietary therapy as a treatment strategy in this setting has not been previously reported. We report the use of dietary strategies using enteral nutrition coupled with the Crohn's Disease Exclus
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TL;DR: Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits of using corticosteroids as mentioned in this paper.
Abstract: Background Pneumonia is a common and potentially serious illness. Corticosteroids have been suggested for the treatment of different types of infection, however their role in the treatment of pneumonia remains unclear. This is an update of a review published in 2011. Objectives To assess the efficacy and safety of corticosteroids in the treatment of pneumonia. Search methods We searched the Cochrane Acute Respiratory Infections Group's Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS on 3 March 2017, together with relevant conference proceedings and references of identified trials. We also searched three trials registers for ongoing and unpublished trials. Selection criteria We included randomised controlled trials (RCTs) that assessed systemic corticosteroid therapy, given as adjunct to antibiotic treatment, versus placebo or no corticosteroids for adults and children with pneumonia. Data collection and analysis We used standard methodological procedures expected by Cochrane. Two review authors independently assessed risk of bias and extracted data. We contacted study authors for additional information. We estimated risk ratios (RR) with 95% confidence intervals (CI) and pooled data using the Mantel-Haenszel fixed-effect model when possible. Main results We included 17 RCTs comprising a total of 2264 participants; 13 RCTs included 1954 adult participants, and four RCTs included 310 children. This update included 12 new studies, excluded one previously included study, and excluded five new trials. One trial awaits classification.All trials limited inclusion to inpatients with community-acquired pneumonia (CAP), with or without healthcare-associated pneumonia (HCAP). We assessed the risk of selection bias and attrition bias as low or unclear overall. We assessed performance bias risk as low for nine trials, unclear for one trial, and high for seven trials. We assessed reporting bias risk as low for three trials and high for the remaining 14 trials.Corticosteroids significantly reduced mortality in adults with severe pneumonia (RR 0.58, 95% CI 0.40 to 0.84; moderate-quality evidence), but not in adults with non-severe pneumonia (RR 0.95, 95% CI 0.45 to 2.00). Early clinical failure rates (defined as death from any cause, radiographic progression, or clinical instability at day 5 to 8) were significantly reduced with corticosteroids in people with severe and non-severe pneumonia (RR 0.32, 95% CI 0.15 to 0.7; and RR 0.68, 95% CI 0.56 to 0.83, respectively; high-quality evidence). Corstocosteroids reduced time to clinical cure, length of hospital and intensive care unit stays, development of respiratory failure or shock not present at pneumonia onset, and rates of pneumonia complications.Among children with bacterial pneumonia, corticosteroids reduced early clinical failure rates (defined as for adults, RR 0.41, 95% CI 0.24 to 0.70; high-quality evidence) based on two small, clinically heterogeneous trials, and reduced time to clinical cure.Hyperglycaemia was significantly more common in adults treated with corticosteroids (RR 1.72, 95% CI 1.38 to 2.14). There were no significant differences between corticosteroid-treated people and controls for other adverse events or secondary infections (RR 1.19, 95% CI 0.73 to 1.93). Authors' conclusions Corticosteroid therapy reduced mortality and morbidity in adults with severe CAP; the number needed to treat for an additional beneficial outcome was 18 patients (95% CI 12 to 49) to prevent one death. Corticosteroid therapy reduced morbidity, but not mortality, for adults and children with non-severe CAP. Corticosteroid therapy was associated with more adverse events, especially hyperglycaemia, but the harms did not seem to outweigh the benefits.
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TL;DR: This commentary discusses hypothetical explanations and takes a step beyond BMI or simple weights alone to present other useful and more specific body composition metrics, such as muscle tissue mass, visceral fat mass, and subcutaneous fat mass.
Abstract: Body mass index (BMI) and simple counts of weight are easy and available tools in the clinic and in research. Recent studies have shown that cancer patients with a low normal BMI (or those with weight loss) have worse outcomes than obese patients. These results suggest that obesity has a protective effect and has been termed the "obesity paradox." In this commentary, we discuss hypothetical explanations and take a step beyond BMI or simple weights alone to present other useful and more specific body composition metrics, such as muscle tissue mass, visceral fat mass, and subcutaneous fat mass. Body composition is highly variable between individuals with significant differences seen between various races and ages. Therefore, it is critical to consider that patients with the exact same BMI can have significantly different body compositions and different outcomes. We encourage further studies to examine body composition beyond BMI and to use other body composition metrics to develop individualized treatments and intervention strategies. Cancer Epidemiol Biomarkers Prev; 26(1); 13-16. ©2017 AACR SEE ALL THE ARTICLES IN THIS CEBP FOCUS SECTION, "THE OBESITY PARADOX IN CANCER EVIDENCE AND NEW DIRECTIONS".
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University of Bologna1, Erasmus University Medical Center2, University of Colorado Denver3, University of Pittsburgh4, Harvard University5, University of Florida6, University of Hawaii7, Kyoto University8, Rambam Health Care Campus9, State University of Campinas10, University of Valle11, Medical University Plovdiv12, Danylo Halytsky Lviv National Medical University13, Sher-I-Kashmir Institute of Medical Sciences14, Universidade Federal de Juiz de Fora15, Tbilisi State Medical University16, Yonsei University17, Catholic University of the Sacred Heart18, Tianjin Medical University19, Mansoura University20, University of Health Sciences Antigua21, College of Health Sciences, Bahrain22, Universidad Nacional de Asunción23, Jagiellonian University24, University of California, San Diego25, University Hospitals Birmingham NHS Foundation Trust26, University of Catania27, Foothills Medical Centre28
TL;DR: This document represents the executive summary of the consensus conference on emergency repair of abdominal wall hernias in adults approved by a WSES expert panel and the guidelines have been revised and updated according to the most recent available literature.
Abstract: Emergency repair of complicated abdominal wall hernias may be associated with worsen outcome and a significant rate of postoperative complications. There is no consensus on management of complicated abdominal hernias. The main matter of debate is about the use of mesh in case of intestinal resection and the type of mesh to be used. Wound infection is the most common complication encountered and represents an immense burden especially in the presence of a mesh. The recurrence rate is an important topic that influences the final outcome. A World Society of Emergency Surgery (WSES) Consensus Conference was held in Bergamo in July 2013 with the aim to define recommendations for emergency repair of abdominal wall hernias in adults. This document represents the executive summary of the consensus conference approved by a WSES expert panel. In 2016, the guidelines have been revised and updated according to the most recent available literature.
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TL;DR: Anti‐adalimumab antibodies (AAA) are associated with loss of clinical response (LOR) and addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy.
Abstract: SummaryBackground
Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking.
Aim
To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients.
Methods
The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as ‘sero-reversal’, elevation of drug levels and regained clinical response were the sought outcomes.
Results
Twenty-three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero-reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero-reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics.
Conclusions
In almost half of inflammatory bowel disease patients developing anti-adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico-biological response. However, these observations need to be confirmed with larger studies.
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TL;DR: Frontal EEG parameters do not readily discriminate volitional responsiveness and unresponsiveness during anaesthesia, and none of the derived depth-of-anaesthesia indices could robustly discrimate IFT responders and non-responders.
Abstract: Background The isolated forearm test (IFT) is the gold standard test of connected consciousness (awareness of the environment) during anaesthesia. The frontal alpha-delta EEG pattern (seen in slow wave sleep) is widely held to indicate anaesthetic-induced unconsciousness. A priori we proposed that one responder with the frontal alpha-delta EEG pattern would falsify this concept. Methods Frontal EEG was recorded in a subset of patients from three centres participating in an international multicentre study of IFT responsiveness following tracheal intubation. Raw EEG waveforms were analysed for power–frequency spectra, depth-of-anaesthesia indices, permutation entropy, slow wave activity saturation and alpha-delta amplitude-phase coupling. Results Volitional responses to verbal command occurred in six out of 90 patients. Three responses occurred immediately following intubation in patients (from Sites 1 and 2) exhibiting an alpha-delta dominant (delta power >20 dB, alpha power >10 dB) EEG pattern. The power–frequency spectra obtained during these responses were similar to those of non-responders (P>0.05) at those sites. A further three responses occurred in (Site 3) patients not exhibiting the classic alpha-delta EEG pattern; these responses occurred later relative to intubation, and in patients had been co-administered ketamine and less volatile anaesthetic compared with Site 1 and 2 patients. None of the derived depth-of-anaesthesia indices could robustly discrimate IFT responders and non-responders. Conclusions Connected consciousness can occur in the presence of the frontal alpha-delta EEG pattern during anaesthesia. Frontal EEG parameters do not readily discriminate volitional responsiveness (a marker of connected consciousness) and unresponsiveness during anaesthesia. Clinical trial registration NCT02248623
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TL;DR: The effectiveness of nivolumab is reasonable yet less prominent than it has been demonstrated in clinical trials, and ECOG PS ≥2 is associated with poor prognosis.
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Virginia Commonwealth University1, The Queen's Medical Center2, University of Pittsburgh3, UC San Diego Health System4, St. Michael's Hospital5, Rambam Health Care Campus6, United Arab Emirates University7, Harvard University8, State University of Campinas9, Foothills Medical Centre10, University of Bergen11, Stavanger University Hospital12, Washington University in St. Louis13, Vanderbilt University Medical Center14, University of Paris15, University of Maryland, Baltimore16
TL;DR: The World Society of Emergency Surgery, Abdominal Compartment Society, and the Donegal Research Academy united a worldwide group of experts in an international consensus conference to review and thereafter propose the basis for evidence-directed utilization of OA management in non-trauma emergency surgery and critically ill patients.
Abstract: The open abdomen (OA) is defined as intentional decision to leave the fascial edges of the abdomen un-approximated after laparotomy (laparostomy). The abdominal contents are potentially exposed and therefore must be protected with a temporary coverage, which is referred to as temporal abdominal closure (TAC). OA use remains widely debated with many specific details deserving detailed assessment and clarification. To date, in patients with intra-abdominal emergencies, the OA has not been formally endorsed for routine utilization; although, utilization is seemingly increasing. Therefore, the World Society of Emergency Surgery (WSES), Abdominal Compartment Society (WSACS) and the Donegal Research Academy united a worldwide group of experts in an international consensus conference to review and thereafter propose the basis for evidence-directed utilization of OA management in non-trauma emergency surgery and critically ill patients. In addition to utilization recommendations, questions with insufficient evidence urgently requiring future study were identified.
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Sheba Medical Center1, Tel Aviv University2, Tel Aviv Sourasky Medical Center3, Rabin Medical Center4, Hebrew University of Jerusalem5, Shaare Zedek Medical Center6, Technion – Israel Institute of Technology7, Rambam Health Care Campus8, Hadassah Medical Center9, Soroka Medical Center10, Emek Medical Center11
TL;DR: In a large real-world Israeli cohort of anti-tumor necrosis factor–experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.
Abstract: BACKGROUND Vedolizumab (VDZ) is an anti-integrin monoclonal antibody effective in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to examine the "real world" efficacy and safety of VDZ in a large national patient cohort. METHODS Patients with inflammatory bowel disease treated with VDZ were prospectively followed for 14 weeks. Patients who completed the induction protocol (week 0/2/6/14) or discontinued the treatment before week 14 for adverse events (AEs) or primary nonresponse were included. The primary outcome was induction of clinical remission at week 14; secondary outcomes included clinical response and corticosteroid-free clinical remission. RESULTS A total of 204 patients (CD-130, UC-69, inflammatory bowel disease-unclassified-5) from 8 centers in Israel were included. Fifteen (7.4%) of the patients were anti-tumor necrosis factor naive and 46 (35.4%) had a previous surgery. For patients with CD, 69/130 (53.1%) responded to treatment; 45 (34.6%) achieved clinical remission; and 38 (29.2%) achieved corticosteroid-free remission at week 14. Fourteen (10.7%) patients discontinued VDZ before week 14 due to primary nonresponse or AEs. For UC, 32/74 (43.2%) responded to treatment; 20 (28.4%) achieved clinical remission, and 18 (24.3%) achieved corticosteroid-free remission at week 14. Fifteen (20.3%) patients with UC did not complete the induction due to primary nonresponse or AEs. AEs were reported by 29 (14.2%) patients (CD and UC combined), most common being nasopharyngitis and skin eruptions. CONCLUSIONS In a large real-world Israeli cohort of anti-tumor necrosis factor-experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.
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TL;DR: Evidence is provided that aging-related neural changes start early in adult life within high-order cognitive networks and in contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline.
Abstract: As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21-85 years old, N=887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21-40 years, mean±SD:25.5±4.8, n=543); middle-aged (41-60 years, 50.6±5.4, n=238); and old (61 years and above, 69.0±6.3, n=106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in internetwork interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life.
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TL;DR: A pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes.
Abstract: APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub-Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D. melanogaster, with no effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human disease risk. We also observed a congruent pattern of cellular damage with tissue-specific expression of APOL1. In particular, expression of APOL1 risk variants in D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic tracer atrial natriuretic factor-red fluorescent protein at early stages and nephrocyte loss at later stages. We also observed differential toxicity of the APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae, including impairment of vacuole acidification. Yeast strains defective in endosomal trafficking or organelle acidification but not those defective in autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of differential injury by the APOL1 risk alleles compared with the nonrisk alleles across evolutionarily divergent species is consistent with an impairment of conserved core intracellular endosomal trafficking processes. This finding should facilitate the identification of cell injury pathways and corresponding therapeutic targets of interest in these amenable experimental platforms.
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TL;DR: There is no high-quality evidence on several cardinal issues in PNM management, including the effectiveness of intraventricular or intrathecal (IV/IT) antibiotics, effectiveness of dual antibiotic therapy for multidrug-resistant Gram-negative bacteria; clinical benefit of routine therapeutic drug monitoring; and safest timing of shunt replacement.
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TL;DR: Findings indicate that functions at intracellular membranes, specifically those of the endoplasmic reticulum and mitochondria, are crucial factors in APOL1 renal risk variant-mediated cell injury.
Abstract: Population genetic approaches have uncovered a strong association between kidney diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism whereby these variants lead to disease manifestation and, in particular, whether this involves an intracellular or extracellular pool of APOL1 remains unclear. Herein, we show a predominantly intracellular localization of APOL1 G0 and the renal risk variants, which localized to membranes of the endoplasmic reticulum in podocyte cell lines. This localization did not depend on the N-terminal signal peptide that mediates APOL1 secretion into the circulation. Additionally, a fraction of these proteins localized to structures surrounding mitochondria. In vitro overexpression of G1 or G2 lacking the signal peptide inhibited cell viability, triggered phosphorylation of stress-induced kinases, increased the phosphorylation of AMP-activated protein kinase, reduced intracellular potassium levels, and reduced mitochondrial respiration rates. These findings indicate that functions at intracellular membranes, specifically those of the endoplasmic reticulum and mitochondria, are crucial factors in APOL1 renal risk variant–mediated cell injury.
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TL;DR: Skeletal muscle mass as assessed from CT imaging was not associated with physical function impairments and skeletal muscle radiodensity was more associated withPhysical function and may aid in identifying older adults at risk for functional impairments.
Abstract: // Grant R. Williams 1, 2 , Allison M. Deal 3 , Hyman B. Muss 2, 3 , Marc S. Weinberg 2 , Hanna K. Sanoff 2, 3 , Kirsten A. Nyrop 2, 3 , Mackenzi Pergolotti 2, 4 , Shlomit Strulov Shachar 2, 5 1 The University of Alabama at Birmingham, Birmingham, AL, USA 2 The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 3 UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA 4 Colorado State University, Fort Collins, CO, USA 5 Division of Oncology, Rambam Health Care Campus, Haifa, Israel Correspondence to: Grant R. Williams, email: gwillia@uab.edu Keywords: sarcopenia, myopenia, skeletal muscle index, cancer, geriatric oncology Received: December 28, 2016 Accepted: March 25, 2017 Published: April 05, 2017 ABSTRACT Background: Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent in older adults and linked with adverse outcomes in cancer, yet the definition and role of sarcopenia remains uncertain. The aim of this study was to examine the association of Computerized Tomography (CT) assessed skeletal muscle measures with physical function in older adults with cancer. Results: CTs for 185 patients were available. Median age 73 (IQR 68–76) and 56.5% female. After controlling for sex and BMI, we found no evidence that SMI was associated with physical function impairments. Both SMD and SMG were associated physical function impairments and higher values were associated with decreased limitations in instrumental activities of daily living (RR 0.84 [CI 0.73–0.96] and 0.94 [CI 0.89–0.99], respectively), climbing stairs (RR 0.84 [CI 0.76–0.94] and 0.91 [CI 0.87–0.96]), walking 1 block (RR 0.77 [CI 0.67–0.90] and 0.91 [CI 0.85–0.97]), and prolonged Timed Up and Go (RR 0.83 [CI 0.75–0.92] and 0.92 [CI 0.88–0.96]). Materials and Methods: Using the Carolina Senior Registry, we identified patients with CT imaging performed within 60 days +/− of baseline geriatric assessment (GA). Skeletal muscle area and density (SMD) were analyzed from L3 lumbar segments. Muscle area and height (m 2 ) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. Conclusions: Skeletal muscle mass as assessed from CT imaging was not associated with physical function impairments. Skeletal muscle radiodensity was more associated with physical function and may aid in identifying older adults at risk for functional impairments.
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TL;DR: A novel 3-protein host-assay’s diagnostic performance for distinguishing between bacterial and viral etiologies is validated in a double-blind, investigator-driven study in febrile children to support its potential to improve antimicrobial treatment decisions.
Abstract: BACKGROUND: Reliably distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse. A novel assay that integrates measurements of blood-borne host-proteins (tumor necrosis factor-related apoptosis-inducing ligand, interferon γ-induced protein-10, and C-reactive protein [CRP]) was developed to assist in differentiation between bacterial and viral disease. METHODS: We performed double-blind, multicenter assay evaluation using serum remnants collected at 5 pediatric emergency departments and 2 wards from children ≥3 months to ≤18 years without ( n = 68) and with ( n = 529) suspicion of acute infection. Infectious cohort inclusion criteria were fever ≥38°C and symptom duration ≤7 days. The reference standard diagnosis was based on predetermined criteria plus adjudication by experts blinded to assay results. Assay performers were blinded to the reference standard. Assay cutoffs were predefined. RESULTS: Of 529 potentially eligible patients with suspected acute infection, 100 did not fulfill infectious inclusion criteria and 68 had insufficient serum. The resulting cohort included 361 patients, with 239 viral, 68 bacterial, and 54 indeterminate reference standard diagnoses. The assay distinguished between bacterial and viral patients with 93.8% sensitivity (95% confidence interval: 87.8%–99.8%) and 89.8% specificity (85.6%–94.0%); 11.7% had an equivocal assay outcome. The assay outperformed CRP (cutoff 40 mg/L; sensitivity 88.2% [80.4%–96.1%], specificity 73.2% [67.6%–78.9%]) and procalcitonin testing (cutoff 0.5 ng/mL; sensitivity 63.1% [51.0%–75.1%], specificity 82.3% [77.1%–87.5%]). CONCLUSIONS: Double-blinded evaluation confirmed high assay performance in febrile children. Assay was significantly more accurate than CRP, procalcitonin, and routine laboratory parameters. Additional studies are warranted to support its potential to improve antimicrobial treatment decisions.
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TL;DR: Advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair are highlighted, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.
Abstract: Podocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3-6, 2016, the 11th International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.
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TL;DR: It is suggested that there may be a role for probiotics in promoting weight loss in adults and weight gain in children, however additional studies are needed.
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University of Bologna1, Rambam Health Care Campus2, University of Jena3, Sapienza University of Rome4, University of Barcelona5, University of Pavia6, Hospital General Universitario Gregorio Marañón7, University of Turin8, University of Zagreb9, University of Naples Federico II10, Museo Nacional Del Prado11
TL;DR: MDRO account for nearly one-third of BSI in cirrhotic patients, often resulting in delayed or inadequate empirical antimicrobial therapy and increased mortality rates, and improved prevention and treatment strategies for MDRO are urgently needed in the liver cirrhosis patients.