Mediastinitis after cardiac surgery

Departamentul Cardiochirurgie SCR, Al XI-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova și cea de-a XXXIII-a Reuniune a Chirurgilor din Moldova „Iacomi-Răzeșu” 27-30 septembrie 2011Scopul lucrării. Mediastenita anterioară după operații pe cord, determină o rată sporită a morbidității, care denotă mărirea costului mediu a cazului tratat a acestui contingent de pacienți. Scopul acestui studiu a fost de a determina cauzele ce condiționează apariția mediastinitei postoperatorie. Metode şi materiale. În perioada anilor 2000 - 2010 au suportat intervenţie chirurgicală pe cord 2634 pacienţi. La 44 (1,67%) de pacienți perioada postoperatorie s-a complicat cu infectarea plăgii. În 22 (50%) cazuri s-a dezvoltat mediastenita anterioară și în 22 (50%) cazuri infectarea plăgii pînă la stern, ulterior s-a dezvoltat mediastinita cu sau fără dehiscența sternului.Grupul de pacienți a fost constituit din 30 (68,1%) bărbați şi 14(31,9%) femei, cu vîrsta medie de 59 de ani. Preoperator 20 (45%) pacienți erau obezi, 6 (13,6%) sufereau de diabet zaharat și 7 (16%) bronhopneumopatie cronică obstructivă. Pentru By-pass aortocoronarian s-a folosit artera toracică internă (ATI) unilateral în 18 (40%) şi bilateral la 1 (2,3%) pacient. Timpul intervenției chirurgicale în mediu a alcătuit 345min. Transfuzii masive postoperator au necesitat 5 (11,3%) pacienți. Diagnosticul de mediastenita a fost stabilit la a 5 - 17 zi postoperator. Restabilirea integrității sternale cu aplicarea procedeului Robicsek s-a efectuat la 14(31,8%) pacienți. A decedat 1 pacient (2,3%) din acest grup, cu mediastinita sero-purulentă la a - 20 zi postoperaror din cauza insuficienței poliorganice. La 4 pacienți s-a dezvoltat osteomielită sternală, care a necesitat tratament de lungă durată (3 - 6 luni). Concluzia: Studiul sugerează că utilizarea ATI uni sau bilaterale, bronhopneumopatie cronica obstructivă, diabetul zaharat, obezitatea, transfuziile masive, timpul îndelungat a operației sunt predictori importanți de mediastinită anterioară.Abstract. Background: Mediastinitis is a serious complication of cardiac surgery. It has a significantsocioeconomic impact and high morbidity. The purpose of this study was to determine perioperative predictors of mediastinitis. Methods and results: From 2634 consecutive pacients, which underwent cardiac surgery in 2000-2010. In forty-four pacients (1.67%) postoperative period was complicated by wound infection. In 22 (50%) cases developed earlier mediastenitis and 22 (50%) cases sternum wound infection subsequently developed mediastinitis with or without dehiscence of the sternum. In this group of pacients 30 were men (68.1%) and 14 women (31.9%) of average age 59 years. Preoperator, 20 (45%) of them had obesity, 6 (13.6%) suffered of diabetes mellitus and 7 (16%) of chronic obstructive pulmonary disease. As a graft for Coronary Artery Bypass (IMA) was used unilaterally 18 (40%) and bilateral 1 (2.3%) pacient. The average time of surgery duration was 345 min. Massive transfusion after surgery was certified on five pacients (11.3%). Diagnosis of Mediastenitis was established at the 5 - 17 days postoperatively. Restoration of sternal integrity with the Robicsek proceeding was performed in 14 (31.8%) pacients.One pacient 1(2.3%) of this group with mediastinitis diet after 20 days postoperative, due to failure Multiple Organ System Dysfunctions. In four pacients developed sternal osteomyelitis, requiring long-term treatment (3-6 months). Conclusion: The present study suggest that uni/bilateral internal mammary artery grafting, chronic obstructive pulmonary disease, obesity, massive transfused units and long surgery duration are important predictors of mediastinitis

CONFIDENCE: achievements and way forward

The project CONFIDENCE (COping with uNcertainties For Improved modelling and DEcision making in Nuclear emergenCiEs) final dissemination event attracted 88 participants to review and discuss the project results and provide ideas for future research work. The workshop highlighted progress in understanding uncertainties in all phases of an emergency. It was also demonstrated that consideration of uncertainties are important when developing countermeasure strategies. Stakeholder engagement as well as societal and ethical aspects in decision making have to be considered. Formal decision making tools were improved and tested. In addition, CONFIDENCE participants, representatives of international organisations and end users, provided their ideas on research needs and the way forward

Mediastinitis after open heart surgery

IMSP Spitalul Clinic RepublicanScopul lucrării: Mediastinita anterioară după operaţii pe cord este asociată cu o rată sporită a morbidităţii, care duce la mărirea costului mediu de spitalizare a acestui contingent de pacienţi. Scopul acestui studiu a fost de a determina predictorii anteriori de dezvoltare a mediastinitei pre-, intra-, şi postoperatorie. Metode: În perioada anilor 2000 – 2012, în Centrul de Chirurgie cardiacă au suportat intervenţie chirurgicală pe cord 3134 pacienţi, dintre care la 46 (1,46%) de pacienţi evoluţia postoperatorie s-a coplicat cu clinică de mediastinită 23 (0.73%) şi infectarea plăgii postoperatorii cu sau fără dehiscenţa sternului 23 (0.73%). Grupul de pacienţi a fost constituit din 31 (67,3%) bărbaţi şi 15 (32,7%) femei, cu vârsta medie de 59 de ani. Preoperatoriu 21 (45%) din ei erau obezi, 8 (17%) aveau diabet zaharat, 31 (67%) bronşită cronică obstructivă. Pentru By-pass aortocoronarian s-a folosit artera toracică internă unilateral (ATI) 21 (45%) şi ATI bilateral la 2 (4%) pacienţi. Timpul intervenţiei chirurgicale a constituit, în mediu 345min. Transfuzii masive postoperatoriu au necesitat doar la 6 (13%) pacienţi. Diagnosticul de mediastinită a fost stabilit la a 5 - 17 zi postoperatoriu. Restabilirea integrităţii sternale cu aplicarea procedeului Robicsek s-a efectuat la 14(30%) pacienţi. Decesul a fost înregistrat la un pacient 1 (2,1%) a 20-a zi postoperator cauzat de mediastinită seropurulentă şi de insuficienţă poliorganică. La 4 pacienţi s-a dezvoltat osteomielită sternală, care a necesitat tratament de lungă durată (3-6 luni). Concluzia: Studiul sugerează că ATI uni sau bilaterale, bronhopneumonia cronica obstructivă, diabetul zaharat, obezitatea, transfuziile masive, timpul îndelungat a operaţiei sunt predicatori importanţi de mediastinită.Background: Mediastinitis is a serious complication of cardiac surgery. It has a significant socioeconomic impact and high morbidity. The purpose of this study was to determine pre-, intra-, and postoperative predictors of mediastinitis. Methods and results: From 3134 consecutive pacients, which underwent cardiac surgery in 2000-2012, forty-six patients (1.46%) developed postoperator mediastinitis 23 (0.73%) and postoperator wound infection with or without dehiscence of the sternum 23 (0.73%). In this group of pacients 31 were men (67,3%) and 15 women (32,7%) of average age 59 years. Preoperative 21 (45%) of them were obes, 8 (17%) suffered of diabetes mellitus and 31 (67%) of chronic obstructive pulmonary disease. As a Coronary Artery Bypass Graft in 21(45%) was used unilateral IMA, and in 2 (4%) cases BIMA. The average duration of surgery was 345min. Massive transfusion after surgery was needed on six patients (13%). Diagnosis of Mediastenitis was established at the 5 - 17 days postoperatively. Restoration of sternal integrity with the Robicsek proceeding was performed in 14 (30%) patients. One patients dead at the 20th day after surgery due to mediastenitis and failure Multiple Organ System Dysfunctions. Four patients developed sternal osteomyelitis, requiring long-term treatment (3-6 months). Conclusion: The present study suggest that uni/ bilateral internal mammary artery grafting, chronic obstructive pulmonary disease, obesity, transfused units and long surgery duration are important predictors of mediastinitis

Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving

The large diversity of cells that comprise the human immune system requires methods that can resolve the individual contributions of specific subsets to an immunological response. Microengraving is process that uses a dense, elastomeric array of microwells to generate microarrays of proteins secreted from large numbers of individual live cells ([similar]10⁴–10⁵ cells/assay). In this paper, we describe an approach based on this technology to quantify the rates of secretion from single immune cells. Numerical simulations of the microengraving process indicated an operating regime between 30 min–4 h that permits quantitative analysis of the rates of secretion. Through experimental validation, we demonstrate that microengraving can provide quantitative measurements of both the frequencies and the distribution in rates of secretion for up to four cytokines simultaneously released from individual viable primary immune cells. The experimental limits of detection ranged from 0.5 to 4 molecules/s for IL-6, IL-17, IFNγ, IL-2, and TNFα. These multidimensional measures resolve the number and intensities of responses by cells exposed to stimuli with greater sensitivity than single-parameter assays for cytokine release. We show that cells from different donors exhibit distinct responses based on both the frequency and magnitude of cytokine secretion when stimulated under different activating conditions. Primary T cells with specific profiles of secretion can also be recovered after microengraving for subsequent expansion in vitro. These examples demonstrate the utility of quantitative, multidimensional profiles of single cells for analyzing the diversity and dynamics of immune responses in vitro and for identifying rare cells from clinical samples.National Institute of Allergy and Infectious Diseases (U.S.) (Award no. 5U19AI050864-07)National Institute of Allergy and Infectious Diseases (U.S.) (Award no. F32AI651003)National Institute of Allergy and Infectious Diseases (U.S.) (Award no. U19AI070352)National Institute of Allergy and Infectious Diseases (U.S.) (Award no. U19AI046130)National Institute of Allergy and Infectious Diseases (U.S.) (Award no. P01AI045757)National Institute of Neurological Disorders and Stroke (U.S.) (Jacob Javits Merit Award (NS2427))Massachusetts Institute of Technology (Texaco- Mangelsdorf Career Development Professor

T Cell Epitope Immunotherapy Induces a CD4(+) T Cell Population with Regulatory Activity

BACKGROUND: Synthetic peptides, representing CD4(+) T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. METHODS AND FINDINGS: In this study we address the mechanism of action of peptide immunotherapy (PIT) in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs) after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4(+) cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4(neg) PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4(+) and CD8(+) PBMCs. CONCLUSION: This study provides evidence for the induction of a population of CD4(+) T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen

Efficacy of the Enquiring About Tolerance (EAT) study among infants at high risk of developing food allergy.

BACKGROUND: The Enquiring About Tolerance (EAT) study was a randomized trial of the early introduction of allergenic solids into the infant diet from 3 months of age. The intervention effect did not reach statistical significance in the intention-to-treat analysis of the primary outcome. OBJECTIVE: We sought to determine whether infants at high risk of developing a food allergy benefited from early introduction. METHODS: A secondary intention-to-treat analysis was performed of 3 groups: nonwhite infants; infants with visible eczema at enrollment, with severity determined by SCORAD; and infants with enrollment food sensitization (specific IgE ≥0.1 kU/L). RESULTS: Among infants with sensitization to 1 or more foods at enrollment (≥0.1 kU/L), early introduction group (EIG) infants developed significantly less food allergy to 1 or more foods than standard introduction group (SIG) infants (SIG, 34.2%; EIG, 19.2%; P = .03), and among infants with sensitization to egg at enrollment, EIG infants developed less egg allergy (SIG, 48.6%; EIG, 20.0%; P = .01). Similarly, among infants with moderate SCORAD (15-<40) at enrollment, EIG infants developed significantly less food allergy to 1 or more foods (SIG, 46.7%; EIG, 22.6%; P = .048) and less egg allergy (SIG, 43.3%; EIG, 16.1%; P = .02). CONCLUSION: Early introduction was effective in preventing the development of food allergy in specific groups of infants at high risk of developing food allergy: those sensitized to egg or to any food at enrollment and those with eczema of increasing severity at enrollment. This efficacy occurred despite low adherence to the early introduction regimen. This has significant implications for the new national infant feeding recommendations that are emerging around the world

A global research priority agenda to advance public health responses to fatty liver disease

Background & aims An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. Methods Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. Results The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of ‘agree’ responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement (‘agree’ + ‘somewhat agree’); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% ‘agree’), 13 priorities had 90% combined agreement. Conclusions Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community’s efforts to advance and accelerate responses to this widespread and fast-growing public health threat. Impact and implications An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat

Age of Information in CSMA-based Networks with Bursty Update Traffic

Exchanging status information between closely located mobile agents is an underlying process in numerous future Cyber Physical Systems (CPS). Real-time updates including positions of neighboring nodes is performed when, for example, autonomous vehicles execute a cooperative maneuver, industrial robots collaborate with each other on a task, or Unmanned Aerial Vehicles (UAVs) execute a mission in a swarm. For the design of networked automatic control strategies in these scenarios, it is essential to understand the performance of such Machine-to-Machine (M2M) communications from the information freshness perspective. To this end, we introduce a mathematical framework which allows characterizing the Age of Information (AoI) in networks governed by the Carrier-Sense Multiple Access (CSMA) protocol. Differently from existing work, we take into account the fact that update packets sent by mobile nodes are not necessarily periodic, since packet triggering is often coupled with agents’ mobility. Our approach is based on the assumption that diverse mobility-triggered message generation patterns can be modeled by a wide class of update traffic arrival processes. We apply Discrete Markovian Arrival Process (DMAP), which is a versatile arrival model able to fit arrival patterns that are modulated by a finite state machine, including bursty traffic. We develop an accurate and efficient analytical model of nodes exchanging one-hop broadcast update messages with bursty arrivals to evaluate the moments as well as entire probability distribution of several performance metrics, including AoI. An asymptotic analysis for large networks suggests a simple way to control the update message rate to minimize the AoI. We show that the optimal update rate that minimizes the mean AoI coincides with the optimum of the wireless channel utilization. Numerical examples point out that the asymptotic theory provides accurate predictions also for small values of the number of nodes