title: Effects of allopurinol on in vivo suppression of arthritis in mice and ex vivo modulation of phagocytic production of oxygen radicals in whole human blood

text: Recently, we demonstrated elevated levels of xanthine oxidase in serum of patients with various inflammatory and autoimmune rheumatic diseases. The present study reports the antiarthritic efficacy of the xanthine oxidase inhibitor and immunosuppressant allopurinol in DBA/1xB10A(4r) mice suffering from peroxochromateinduced arthritis. A profound dose-dependent suppression of arthritis was noted (P <0.001). The ED(50) was 80±14μmol/kg/day. The arthritis index correlated positively to the phagocytic production of oxygen radicals (r (2)>0.672) and negatively to the concentration of allopurinol (r (2)=0.915). Ex vivo, allopurinol and various conventional antirheumatic drugs were screened for the inhibition of 12-otetradecanoylphorbol-13-acetate-stimulated whole human blood chemiluminescence. The concentrations of antirheumatic drugs required to inhibit the chemiluminescence by 50% were compared to the therapeutic doses administered to rheumatic patients. Whiled-penicillamine andcis-platinum(II) increased the phagocytic generation of superoxide, nonsteroidal antiinflammatory drugs (NSAIDs), steroids, and slow-acting antirheumatic drugs (SAARDs) inhibited the whole blood chemiluminescence in a dose-dependent manner. Therapeutic doses of NSAIDs, SAARDs, or steroids inhibited the phagocytic generation of reactive oxygen species by 10–50%. In addition to well-known mechanisms of action of NSAIDs and SAARDs, our results support the hypothesis that most common anti-rheumatic drugs act also by modulating the levels of reactive oxygen species, which serve important mediator and signal transduction functions in inflammatory and autoimmune diseases. Pharmacologically safe antioxidants like allopurinol, which simultaneously modify the oxidative burst of phagocytes, inhibit xanthine oxidase, and display immunosuppressive effects may well be suited to control the consequences of chronic phagocytic hyperreactivity in rheumatic patients.


title: Prospective observational cohort study of cerebrovascular CO(2) reactivity in patients with inflammatory CNS diseases

text: The purpose of this study was to evaluate the significance of cerebrovascular CO(2) reactivity (CO(2) R) in the course and outcome of inflammatory central nervous system (CNS) diseases. Sixty-eight patients with inflammatory CNS diseases and 30 healthy volunteers were included in this prospective observational cohort study. The observational period was between January 2005 and May 2009. The CO(2) R was measured by transcranial Doppler (TCD) ultrasound using the breath-holding method. We compared patients with normal CO(2) R (breath-holding index [BHI(m)] ≥ 1.18 = BHI(N) group) with patients who showed impaired CO(2) R (BHI(m) < 1.18 = BHI(R) group). We also analyzed the association of impaired CO(2) R with the etiology, severity, and outcome of disease. When compared to the BHI(N) group, the patients from the BHI(R) group were older, had a heavier consciousness disturbance, experienced more frequent respiratory failure, and, subsequently, had worse outcomes. There were no fatalities among the 28 patients in the BHI(N) group. The comparison of subjects with bacterial and non-bacterial meningitis revealed no significant differences. The unfavorable outcome of disease (Glasgow Outcome Scale [GOS] score 1–3) was significantly more common in subjects with impaired CO(2) R (62.5% vs. 10.7%). Logistic regression analysis was performed in order to establish the prognostic value of BHI(m). The outcome variable was unfavorable outcome (GOS 1–3), while the independent variables were age, Glasgow Coma Scale (GCS) score, and BHI(m). The age and BHI(m) showed the strongest influence on disease outcome. A decrease of BHI(m) for each 0.1 unit increased the risk of unfavorable outcome by 17%. Our study emphasizes the importance of CO(2) R assessment in patients with inflammatory CNS diseases.


title: Human herpes virus co-infection is associated with mortality in HIV-negative patients with Pneumocystis jirovecii pneumonia

text: The purpose of this investigation was to characterize the management and prognosis of severe Pneumocystis jirovecii pneumonia (PJP) in human immunodeficiency virus (HIV)-negative patients. An observational cohort study of HIV-negative adults with PJP documented by bronchoalveolar lavage (BAL) through Gomori–Grocott staining or immunofluorescence, admitted to one intensive care unit (ICU) for acute respiratory failure, was undertaken. From 1990 to 2010, 70 patients (24 females, 46 males) were included, with a mean age of 58.6 ± 18.3 years. The mean Simplified Acute Physiology Score (SAPS)-II was 36.9 ± 20.4. Underlying conditions included hematologic malignancies (n = 21), vasculitis (n = 13), and solid tumors (n = 13). Most patients were receiving systemic corticosteroids (n = 63) and cytotoxic drugs (n = 51). Not a single patient received trimethoprim–sulfamethoxazole as PJP prophylaxis. Endotracheal intubation (ETI) was required in 42 patients (60.0 %), including 38 with acute respiratory distress syndrome (ARDS). In-ICU mortality was 52.9 % overall, reaching 80.9 % and 86.8 %, respectively, for patients who required ETI and for patients with ARDS. In the univariate analysis, in-ICU mortality was associated with SAPS-II (p = 0.0131), ARDS (p < 0.0001), shock (p < 0.0001), and herpes simplex virus (HSV) or cytomegalovirus (CMV) on BAL (p = 0.0031). In the multivariate analysis, only ARDS was associated with in-ICU mortality (odds ratio [OR] 23.4 [4.5–121.9], p < 0.0001). PJP in non-HIV patients remains a serious disease with high in-hospital mortality. Pulmonary co-infection with HSV or CMV may contribute to fatal outcome.


title: Granulomatosis with polyangiitis: clinical course and outcome of 60 patients from a single center in South India

text: Granulomatosis with polyangiitis (GPA) previously known as Wegener’s granulomatosis is one of the forms of idiopathic systemic vasculitis. There is very scanty data available on GPA in Asian and Indian population. We studied data of 60 patients from southern India, diagnosed with GPA to describe the physical characteristics, the treatment, and outcome. Patients who fulfilled any two of the four criteria proposed by the American College of Rheumatology, and those with clinical features of GPA with ANCA positivity and histopathological confirmation, were included in the study. Disease activity and damage were assessed by Birmingham Vasculitis Activity Score v. 3 (BVAS v. 3) and Vasculitis Damage Index (VDI), respectively. Relapses were defined as recurrence of GPA of sufficient severity to require treatment or increase in the dose of treatment on a patient who was previously stable. Out of 60 patients, initial BVAS evaluation showed that 57 (95%) patients had severe disease and 3 (5%) patients had limited disease where median BVAS was 21.5 (range 17–44). Follow-up BVAS evaluation for severe disease showed that 13 (22.8%) patients continued with severe disease of which 9 patients did not survive, 24 (42.3%) had remission, 11 (19.2%) had persistent disease, and 9 (15.7%) were lost to follow-up. The mean VDI score was 2.5 ± 2. Renal involvement was established in 42 (70%) patients. Upper and lower respiratory involvement was seen in 38 (63%) patients. Nervous system involvement was noted in the 15 (25%) patients. Articular manifestations were seen in 16 (27%) patients. Diverse clinical manifestation delay early diagnosis and treatment of this potentially treatable vasculitis. Focused approach could expedite early diagnosis and can reduce the mortality.


title: Bone marrow transplantation from alternative donors for thalassemia: HLA-phenotypically identical relative and HLA-nonidentical sibling or parent transplants

text: Twenty-nine patients with thalassemia and a median age of 6 years (range 1.1–33 years) were given a BMT from an alternative donor. Six of the 29 donors were HLA-phenotypically identical and two were mismatched relatives, 13 were mismatched siblings and eight were mismatched parents. Six patients received no antigen (relatives), 15 patients one antigen, five patients two antigen and three patients three antigen disparate grafts. Twenty-three patients were in class 2 or class 3, whereas six patients were in class 1. Thirteen patients were given BUCY, nine patients BUCY plus ALG, six patients BUCY plus TBI or TLI and one patient BUCY with prior cytoreductive-immunosuppressive treatment as conditioning. As GVHD prophylaxis four patients received MTX, 22 CsA + MTX + methylprednisolone (MP) and three patients CsA + MP. Thirteen of 29 patients (44.8%) had sustained engraftment. The probability of graft failure or rejection was 55%. There were no significant differences between antigen disparities and graft failure. The incidence of grade II–IV acute GVHD was 47.3% and chronic GVHD was 37.5%. The incidence of acute GVHD was higher in patients receiving one or two antigen disparate in the GVHD direction grafts (vs no antigen) (P EQ 0.04; odds ratio 10.8; 95% CI 1.5–115). The probability of overall and event-free survival was 65% and 21%, respectively, with median follow-up of 7.5 years (range 0.6–17 years) for surviving patients. The degree of HLA disparity between patient and donor did not have a significant effect on survival. The incidence of nonhematologic toxicity was low. Transplant-related mortality was 34%. GVHD (acute or chronic) was a major contributing cause of death (50%) followed by infections (30%). We conclude that at present, due to high graft failure and GVHD rates, BMT from alternative donors should be restricted to patients who have poor life expectancies because they cannot receive adequate conventional treatment or because of alloimmunization to minor blood antigens. Bone Marrow Transplantation (2000) 25, 815–821.


Evaluation of TNF as antiviral, antibacterial and antiparasitic agent


title: Apoptotic neutrophils undergoing secondary necrosis induce human lung epithelial cell detachment

text: Clearance of apoptotic neutrophils by alveolar macrophages plays an important role in the resolution phase of lung inflammation. If not cleared, apoptotic neutrophils are postulated to release histotoxic granular contents. Since numerous cellular proteins are degraded during apoptosis, we sought to determine whether functional serine proteinases are indeed released by apoptosing neutrophils in vitro. In a coculture system, cytokine-activated neutrophils induced detachment in the human epithelial cell line, A549. This process was CD18- and serine proteinase-dependent. Early apoptotic neutrophils induced significant detachment, but live, senescent, resting neutrophils and terminal, secondary necrotic neutrophils had a different effect. This detachment process was CD18-independent but serine proteinase-dependent. Similarly, detachment occurred with primary human small airway epithelial cells. Notably, epithelial cell detachment correlated with the transition of early apoptotic neutrophils to secondary necrosis and with the accumulation of elastase in the supernatant. The membrane integrity of lung epithelial cells was damaged in advance of significant cell detachment. These observations suggest that not only live activated neutrophils but also apoptosing neutrophils can reveal functional elastase activities. Furthermore, the rapidity of the transition emphasizes the importance of the prompt clearance of apoptotic neutrophils before they progress to secondary necrosis at the site of lung inflammation.


docid: xeazvkdt

title: „Off-label use“ in der Herzchirurgie

text: In the view of off-label use, special concern should be granted to obtaining informed consent from the patient. It is important to point out the test character of the treatment. The patient has to be informed about the risks that exist with the treatment. The patient has to know that a drug not yet approved for this treatment is being used and the risks linked with its use have to be addressed. In addition, informed consent has to be documented and the differences compared with the standard treatment have to be pointed out.


title: T follicular regulatory cells infiltrate the human airways during the onset of acute respiratory distress syndrome and regulate the development of B regulatory cells

text: T follicular regulatory (Tfr) cell is a CXCR5(+)Foxp3(+) subset of T regulatory (Treg) cell with critical roles in regulating germinal center responses and modulating the immune environment in the lymph nodes. Studies have shown that the proportion of Tfr cells may increase during acute inflammation. In this study, we investigated the role of Tfr cells in acute respiratory distress syndrome (ARDS). We found that Tfr cells were significantly enriched in peripheral blood and in mini-bronchoalveolar lavage (BAL) during the onset of ARDS. Notably, Tfr cells represented the majority of Treg cells in the mini-BAL samples. Tfr cells also showed CTLA-4, IL-10, and TGF-β expression, but compared to the non-Tfr Treg cells, the CTLA-4 and IL-10 expression by Tfr cells were slightly reduced. Both Tfr cells and non-Tfr Treg cells suppressed the proliferation of autologous CD4(+)CD25(−) T cells; however, the Tfr cells displayed slightly reduced suppression capacity. Subsequently, B cells were co-incubated with autologous Tfr cells or non-Tfr Treg cells. Interestingly, we found that the frequency of IL-10(+) Breg cells was significantly higher following incubation with Tfr cells than with non-Tfr Treg cells, which suggested that Tfr cells were more potent at inducing IL-10(+) Breg cells. Together, these results demonstrated that Tfr cells were a similar but distinctive subset of Treg cells. Given that Tfr cells were strongly enriched in ARDS patients, especially in the lung infiltrates, they may exert critical ameliorating effects in ARDS.


title: Diagnostic value of direct examination of protected specimen brush samples in nosocomial pneumonia

text: The value of direct examination of Giemsa and Gram stains of cytospin preparations of protected specimen brush samples was compared to that of quantitative culture. Sixty-one samples from patients suspected to have nosocomial pneumonia were analysed. Twenty-five samples were positive by quantitative culture, 21 of which contained microorganisms seen by direct examination. The presence of leucocytes was not specific for a positive culture, but in their absence, a positive culture was unlikely. The presence of intracellular organisms always correlated with a positive culture, but was not very sensitive.


title: Executive Dysfunction Following Critical Illness: Exploring Risk Factors and Management Options in Geriatric Populations

text: Cognitive impairment is a common occurrence that has been shown to occur in over 50 % of patients following critical illness. This impairment occurs across a range of domains including attention, memory, processing speed, and executive dysfunction. In this article, we will discuss the pathophysiology behind cognitive impairment including hypoxemia and cytokines. Secondly, we will describe the risk factors for cognitive impairment including age, length of stay, and delirium. Lastly, we will review emerging data related to the use of cognitive rehabilitation, formation of postintensive care clinics in qualifying patients, and potential neuropharmacologic therapy. While our chapter focuses on cognitive impairment generally, it places a particular emphasis on executive dysfunction, not because impairment occurs solely in this domain but because impairments of an executive nature may be uniquely debilitating.


Procalcitonin — A new indicator of the systemic response to severe infections


Reply to swine flu and hemophagocytic syndrome


title: Downregulation of Paralemmin-3 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Rats by Regulating Inflammatory Response and Inhibiting Formation of TLR4/MyD88 and TLR4/TRIF Complexes

text: Previous studies have demonstrated paralemmin-3 (PALM3) participates in Toll-like receptor (TLR) signaling. This study investigated the effect of PALM3 knockdown on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its underlying mechanisms. We constructed a recombinant adenoviral vector containing short hairpin RNA for PALM3 to knockdown PALM3 expression. A transgene-free adenoviral vector was used as a negative control. The ALI rat model was established by LPS peritoneal injection at 48-h post-transfection. Results showed that downregulation of PALM3 improved the survival rate, attenuated lung pathological changes, alleviated pulmonary edema, lung vascular leakage and neutrophil infiltration, inhibited the production of proinflammatory cytokines and activation of nuclear factor κB and interferon β regulatory factor 3, and promoted the secretion of anti-inflammatory cytokine interleukin-10 and expression of suppressor of cytokine signaling-3 in the ALI rat model. However, PALM3 knockdown had no effect on TLR4, myeloid differentiation factor 88 (MyD88), and Toll-interleukin-1 receptor domain-containing adaptor inducing interferon β (TRIF) expression. Moreover, PALM3 knockdown reduced the interaction of TLR4 with MyD88 or TRIF induced by LPS in rat lungs. Therefore, the downregulation of PALM3 protected rats from LPS-induced ALI and its mechanisms were partially associated with the modulation of inflammatory responses and inhibition of TLR4/MyD88 and TLR4/TRIF complex formation.


title: Exhaled nitric oxide and pulmonary complications after paediatric stem cell transplantation

text: Pulmonary complications are major causes of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). We hypothesise that elevated exhaled nitric oxide (FeNO) levels early after HSCT in children are predictive for pulmonary complications. The present prospective study included 30 children (age, 4–18 years) before HSCT. FeNO levels were evaluated 10 days before transplant, at day 0, day +28 and day +60 after HSCT. During the follow-up period until day +100, pulmonary complications and lung function were assessed. Before HSCT, the mean FeNO levels were comparable in children with or without post-transplant pulmonary complications. However, they differed at day 0 and day +28 with a mean of 7 (±1.95) and 13 (±3.44) ppb at day 0 and a mean of 13 (±3.44) and 14 (±3.57) ppb at day +28, respectively. Conclusion: Children with pulmonary complications after day +28 have higher mean FeNO levels 28 days after HSCT than children without later pulmonary complications. Therefore, FeNO could be an important diagnostic tool for hyperinflammatory response in bronchial epithelium after paediatric HSCT.


title: Relevance of granulocyte apoptosis to resolution of inflammation at the respiratory mucosa

text: The respiratory mucosa is responsible for gas exchange and is therefore, of necessity, exposed to airborne pathogens, allergens, and foreign particles. It has evolved a multi-faceted, physical and immune defense system to ensure that in the majority of instances, potentially injurious invaders are repelled. Inflammation, predominantly mediated by effector cells of the granulocyte lineage including neutrophils and eosinophils, is a form of immune defense. Where inflammation proves unable to remove an inciting stimulus, chronic inflammatory disease may supervene because of the potential for tissue damage conferred by the presence of large numbers of frustrated, activated granulocytes. Successful recovery from inflammatory disease and resolution of inflammation rely on the clearance of these cells. Ideally, they should undergo apoptosis prior to phagocytosis by macrophage, dendritic, or epithelial cells. The outcome of inflammation can have serious sequelae for the integrity of the respiratory mucosa leading to disease. Therapeutic strategies to drive resolution of inflammation may be directed at the induction of granulocyte apoptosis and the enhancement of granulocyte clearance. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/mi.2008.31) contains supplementary material, which is available to authorized users.


title: Diagnostic and Prognostic Values of Admission Procalcitonin Levels in Community–Acquired Pneumonia in an Intensive Care Unit

text: BACKGROUND: Measurement of procalcitonin (PCT) has been studied for several years in infectious diseases. Some studies have focused on community–acquired pneumonia (CAP) but only one was conducted in critically ill patients hospitalized in an intensive care unit (ICU). PATIENTS AND METHODS: To determine the diagnostic and prognostic role of PCT in patients admitted in an intensive care unit for severe CAP, 110 patients hospitalized in our unit were prospectively studied. Within 48 hours following ICU admission, PCT serum level was measured with a quantitative method above a threshold value of 0.5 ng/ml. RESULTS: Initially focusing on the diagnostic value of PCT, 20% of the patients had a serum PCT level < 0.5 ng/ml, 30% between 0.5 ng/ml and 2 ng/ml, and 50% ≥ 2 ng/ml. Serum PCT level was higher in microbiologically documented CAP (median = 4.9 ng/ml vs 1.5 ng/ml if no bacteria were found; p = 0.001), but was not predictive of any specific bacterial agent. Concerning the prognostic value, the serum PCT level was higher for bacteremic patients and/or septic shock patients (4.9 ng/ml vs 1.5 ng/ml; p = 0.0003). Moreover, PCT levels were increased in patients who developed, during their ICU stay, infection–related complications (septic shock, multiorgan dysfunction, acute respiratory distress syndrome and disseminated intravascular coagulation). Finally, the initial PCT level was significantly higher in patients who died during the ICU stay (5.6 ng/ml vs 1.5 ng/ml; p < 0.0001). Such a relationship was not found with C–reactive protein (CRP). CONCLUSION: In ICU patients admitted for severe CAP, initial PCT values could be an interesting predictor for complications and mortality.


title: The role of inflammation in the development of chronic lung disease in neonates

text: Chronic lung disease (CLD) has been associated with chorioamnionitis and upper respiratory tract colonisation with Ureaplasma urealyticum. The aim of this review is to describe the increasing evidence that inflammation plays a critical role in the early stages of CLD of the neonate. Ongoing lung damage in the premature infant may be caused by failure to downregulate and control this inflammatory response. Tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-8 are important pro-inflammatory cytokines of which IL-8 is an important chemotactic factor in the lung. Data suggest that preterm newborns with lung inflammation may be unable to activate the anti-inflammatory cytokine IL-10. Therefore, early post-natal anti-inflammatory therapy could help in preventing development of CLD. Prophylactic dexamethasone therapy cannot yet be recommended. There are a number of potential interactions between surfactant and cytokine effects on the preterm lung which have not been evaluated. Surfactant protein A may be an important modulator of the immune response to lung injury. The role of high-frequency ventilation in the prevention of CLD still remains unclear. Conclusion Many aspects of the pathogenesis of the inflammatory response in the development of chronic lung disease remain to be elucidated. Further research to identify preterm infants at highest risk for the development of this multifactorial and complex disease is needed.


title: Effects of in vivo Soluble Selectin Gene Introduction on LPS-Induced Leukocyte Accumulation in the Murine Lung

text: The selectin family adhesion molecules exert a crucial role in accumulation of leukocytes at the site of inflammation. To test the biological effects of soluble selectin on lung inflammation, we introduced an expression plasmid vector of soluble selectin gene via HVJ-liposome into a murine model of LPS-induced lung injury. The myeloperoxidase activity in LPS-injected mice was suppressed by the in vivo injection of soluble P-selectin gene relative to control mice. On the contrary, soluble E- or L-selectin genes did not exert suppressive effects. Our observations suggest that P-selectin plays a crucial role in the initial steps of lung inflammation, and exogenous introduction of soluble P-selectin by in vivo gene transfer method may be a useful strategy for regulating inflammation of the lung.


title: Clinical Characteristics and Outcomes of Primary Immunodeficiencies in Thai Children: An 18-year Experience from a Tertiary Care Center

text: INTRODUCTION: Early diagnosis and treatment are keys to improve survival of patients with primary immunodeficiency diseases (PID). The clinical characteristics of these patients in Thailand were not well defined. OBJECTIVE: This study aimed to determine the clinical characteristics and outcomes of patients with PID in Thailand. METHODS: Medical records of PID patients in the past 18 years were reviewed. RESULTS: Sixty-seven children were registered. Antibody deficiencies were the most common PID (52.2%), followed by combined T cell and B cell immunodeficiencies (25.4%), other well-defined immunodeficiency syndromes (11.9%), and phagocytic defects (10.4%). The most common presentations of antibody deficiencies, combined T cell and B cell immunodeficiencies, and phagocytic defects were infection in the upper respiratory tract (74.3%), gastrointestinal tract (82.4%), and skin (85.7%), respectively. The highest mortality rate (52.9%) was found in severe combined immunodeficiency. CONCLUSION: These results provide clinical features of PID in Thailand. Knowing these features will lead to prompt diagnosis and appropriate management.


Zur Medienberichterstattung über den in Österreich verfügbaren Impfstoff gegen pandemische Influenza A/H1N1


docid: dernekty

title: Phenylalanine and Tyrosine Kinetics in Critically Ill Children with Sepsis

text: ABSTRACT: To better understand the impact of severe illness on the amino acid economy and nutritional needs of pediatric patients, we studied plasma phenylalanine and tyrosine kinetics in eleven critically ill patients (six full-term newborns and five young infants). Within 48 h of the diagnosis of sepsis they were given primed constant i.v. infusions of L-[1-(13)C]phenylalanine and L-[3,3,(2)H(2)]tyrosine for 4 h. Routine nutritional support continued during this period by parentcral administration of dextrose, lipid emulsion, and an amino acid mixture low in tyrosine. Phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation did not differ significantly between the two age groups, and so the data were combined for evaluation. For the entire group, values (μmol-kg(−1)-h(−1); mean ± SD) for phenylalanine and tyrosine fluxes and rate of phenylalanine hydroxylation were 132 ± 24, 66 ± 16, and 29 ± 12, respectively. Plasma phenylalanine to tyrosine concentration ratio was 1.67 ± 0.6. From a comparison of the rate of phenylalanine hydroxylation with measured phenylalanine intakes, it was concluded that their routine, clinical nutritional support was inadequate to achieve body phenylalanine balance. In comparison with published data, the relative rate of phenylalanine hydroxylation appears to be high. We speculate that tyrosine is a conditionally indispensable amino acid under these conditions; it would be desirable to establish the intake levels and ratio of phenylalanine to tyrosine that effectively support aromatic amino acid balance in these critically ill patients.


title: Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors

text: The development of new mechanisms of resistance among pathogens, the occurrence and transmission of genes responsible for antibiotic insensitivity, as well as cancer diseases have been a serious clinical problem around the world for over 50 years. Therefore, intense searching of new leading structures and active substances, which may be used as new drugs, especially against strain resistant to all available therapeutics, is very important. Dihydrofolate reductase (DHFR) has attracted a lot of attention as a molecular target for bacterial resistance over several decades, resulting in a number of useful agents. Trimethoprim (TMP), (2,4-diamino-5-(3′,4′,5′-trimethoxybenzyl)pyrimidine) is the well-known dihydrofolate reductase inhibitor and one of the standard antibiotics used in urinary tract infections (UTIs). This review highlights advances in design, synthesis, and biological evaluations in structural modifications of TMP as DHFR inhibitors. In addition, this report presents the differences in the active site of human and pathogen DHFR. Moreover, an excellent review of DHFR inhibition and their relevance to antimicrobial and parasitic chemotherapy was presented.


title: The FGF metabolic axis

text: Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.


title: Impact of comorbidity on outcomes and overall survival after open and minimally invasive esophagectomy for locally advanced esophageal cancer

text: BACKGROUND: The aim of this study was to examine the impact of the Charlson Comorbidity Index-Grade (CCI-G) on predicting outcomes and overall survival after open and minimally invasive esophagectomy (MIE). METHODS: One hundred and forty-six patients who underwent esophagectomy between 1995 and 2011 for stage II and III cancer were selected and separated into open esophagectomy (Open) and MIE groups. Risk adjustment was performed using the CCI-G. The outcomes of interest were operative time, estimated blood loss (EBL), lymph node harvest, length of hospital stay (LOS), major complications, 30-day mortality, and overall survival. RESULTS: Sixty-four patients (44 %) underwent Open while 71 (49 %) had MIE. An additional (7 %) were converted and classified with MIE. There was no significant difference between MIE and Open in terms of operative time. MIE had less EBL (mean difference = 234 mL, p < 0.001), higher lymph node harvest (mean = 7.4 nodes, p < 0.001), and shorter LOS (median = 1.5 days, p = 0.02). Atrial arrhythmias were the most frequent complication, occurring in 33 % of patients in both the MIE and the Open group (p = 0.988). Thirty-day mortality was 2 % for MIE and 5 % for Open (p = 0.459). Five-year survival was 41 % for MIE and 33 % for Open (p = 0.513). Operative approach, age, gender, BMI, clinical stage, and neoadjuvant therapy did not have any significant effect on the outcomes or overall survival. CCI-G influenced outcomes with operative time, LOS, cardiovascular complication, and anastomotic leak rate, favoring CCI-G 0 compared to CCI-G 3. Overall survival was worse for CCI-G 1 in comparison with CCI-G 0 [hazard ratio (HR) 1.99, p = 0.027]. CONCLUSIONS: MIE is a safe alternative to open esophagectomy for the treatment of locally advanced esophageal cancer. The presence of comorbidities increased operative time, length of hospital stay, and postoperative complications while worsening overall survival.


title: Surveillance of the first case of human avian influenza A (H7N9) virus in Beijing, China

text: PURPOSE: Human infections with avian influenza A (H7N9) virus manifested in China in March 2013. The first case infected with H7N9 virus in Beijing involved a family member of a chicken dealer and was reported in April 2013. The clinical and epidemiological characteristics of this case and her parents were examined to illustrate some key traits regarding this novel H7N9 virus. METHODS: The index case was subjected to intensive clinical examination in order to observed the clinical process. Real-time PCR was used to confirm cases infected with H7N9 virus. The index case was administered oseltamivir (45 mg, twice daily) at the early stage of the infection. Sera were collected from the index case and her parents from the onset of illness onwards. The subjects were followed for 4 weeks. RESULTS: The sera were confirmed by neutralizing antibody tests. The index case’s clinical manifestation progressed quickly. The pharyngeal swab tested positive for influenza A based on the detection of influenza A antigen (rapid influenza diagnostic test) 15 h after the onset of fever and was positive for H7N9 virus. The patient’s temperature dropped to 36.2 °C 18 h after treatment by oseltamivir (32 h after fever). Cough and other symptoms alleviated rapidly. A number of specimens from the environment of this cluster and from the feces specimens tested positive for viral RNA of the H7N9 virus on the fourth day following onset of the index case’s illness. Pharyngeal swabs of the mother tested positive for H7N9 virus twice, but she showed no clinical symptoms. Four weeks after disease onset, the family did not present any clinical symptoms, and the results of the physical examination and blood tests were normal. The mother and the case’s sera had a fourfold increased neutralizing antibody titer. CONCLUSION: Early diagnosis and early initiation of the treatment of confirmed infections is the most effective strategy for managing H7N9 virus infection. Human beings exposed to H7N9 virus may develop asymptomatic infection.


title: Infektionen als Notfall der Onkologie: Übersicht über die aktuellen Leitlinien

text: BACKGROUND: Patients with oncologic diseases, particularly those with hematologic malignancies, are at an increased risk of common infections and unique treatment-related complications with high mortality and morbidity. The annual incidence and prevalence of cancer in Germany is rising. Although modern treatments have generally led to improved survival, increasing age, comorbidities, and frailty of the patients require multidisciplinary strategies for handling complex therapeutic concepts and treatment of the associated complications. METHODS: A selective literature search and guidelines from the European Society for Medical Oncology (ESMO), the German Society of Hematology and Medical Oncology (Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, DGHO), the Infectious Diseases Working Group of the DGHO (Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie, AGIHO), and the American Society of Clinical Oncology (ASCO) formed the basis of this study. CONCLUSION: Recognition of severe infections in cancer patients and their discrimination from treatment-associated complications is a challenge. Neutropenic fever is the most frequent infectious emergency in oncology. Early empiric treatment with broad-spectrum antibiotics and escalated diagnostic strategies are needed to successfully treat this vulnerable patient group. In this article, a range of potentially life-threatening infections in immunocompromised patients are discussed.


title: Challenges in the Diagnosis of Invasive Fungal Infections in Immunocompromised Hosts

text: PURPOSE OF REVIEW: The expanding population of immunocompromised patients coupled with the recognition of a growing number of different species of fungi responsible for diseases in such hosts makes the diagnosis of invasive fungal infection (IFI) a challenging task. The recent advances and challenges in the diagnosis of IFI in the setting of immunocompromised hosts are reviewed. The advantages and limitations of histopathology and the role of culture-independent methods, such as those based on the use of nucleic acids applied to fresh and formalin-fixed, paraffin-embedded sections, besides culture- and non-culture-based diagnostic methods, to obtain a timely and correct diagnosis of IFI are highlighted. RECENT FINDINGS: The therapeutic implications of identifying the genus and species of the fungus present in the specimen with the molecular diagnostics applied to tissue specimens are reviewed. No method alone is efficient in correctly identifying fungi and it is essential to combine the traditional histochemical staining with molecular methods to achieve a rapid and genus-/species-specific diagnosis of IFI. SUMMARY: We review the recent findings and challenges in the hystopathologic diagnosis of IFI in the setting of immunocompromised hosts. Non method alone is efficient in correctly identify fungi and pathologists should combine classic staining with molecular methods to achieve a rapid and genus/species fungal diagnosis.


docid: cpqmdung

title: Evidence-Based Support for Nutrition Therapy in Head and Neck Cancer

text: PURPOSE OF REVIEW: Patients diagnosed with head and neck (H&N) cancer often present in a malnourished state for varied reasons; nutritional optimization is therefore critical to the success of treatment for these complex patients. This article aims to review the current nutrition literature pertaining to H&N cancer patients and to present evidence-based strategies for nutritional support specific to this population. RECENT FINDINGS: Aggressive nutritional intervention is frequently required in the H&N cancer patient population. Rehabilitating nutrition during operative and nonoperative treatment improves compliance with treatment, quality of life, and clinical outcomes. When and whether to establishing alternative enteral access are points of controversy, although recent evidence suggests prophylactic enteral feeding tube placement should not be universally applied. Perioperative nutritional optimization including preoperative carbohydrate loading and provision of arginine-supplemented immunonutrition has been shown to benefit at-risk H&N cancer patients. SUMMARY: With multidisciplinary collaboration, H&N cancer patients can receive individualized nutritional support to withstand difficult cancer treatment regimens and return to acceptable states of nutritional health.


title: Dengue Hemorrhagic Fever: A State-of-the-Art Review Focused in Pulmonary Involvement

text: Dengue fever is an arboviral disease transmitted to humans through the bites of infected female Aedes mosquitoes. Dengue virus is a member of the Flaviviridae family, and human infection can be caused by any of the four antigenically distinct serotypes (DENV 1–4). The infection has become recognized as the most important and prevalent arboviral disease in humans, endemic in almost 100 countries worldwide. Nearly 3 billion people live in areas with transmission risk. Autochthonous transmission of the virus in previously disease-free areas, increased incidence in endemic areas, and epidemic resurgence in controlled regions could increase the risk of contracting more severe forms of the disease, such as dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Symptomatic dengue virus infection can present with a wide range of clinical manifestations, from mild fever to life-threatening DSS. Thoracic complications may manifest as pleural effusion, pneumonitis, non-cardiogenic pulmonary edema, and hemorrhage/hemoptysis. No vaccine is currently available and no specific treatment for dengue fever exists, but prevention and prompt management of complications in patients with DHF can help reduce mortality. This review describes the main clinical, pathological, and imaging findings of thoracic involvement in DHF.


title: Endemic Mycoses: What’s New About Old Diseases?

text: Infections with geographically constrained dimorphic fungi cause the endemic mycoses, which include blastomycosis, coccidioidomycosis, emmonsiosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and penicilliosis. In the last 5 years, our understanding of the epidemiology, diagnostics, and to a lesser extent management of these diseases has advanced. Specifically, the application of molecular techniques for genotyping fungal pathogens has resulted in the recognition of cryptic species within several genera, including Blastomyces, and Paracoccidioides; the reclassification of Penicillium marneffei, the agent of penicilliosis, to the genus Talaromyces; and the global emergence of dimorphic fungi of the genus Emmonsia, cause disease in immunocompromised persons. New and refined diagnostic tests are available based on the detection of circulating antigens and antibodies, mass spectrometry, and targeted gene amplification. In contrast, the development of new therapeutic options remains stalled, although isavuconazole may hold promise. Finally, advances have been made in the prospect of viable vaccines for preventing animal and human disease.


title: Effects of bile acids and endotoxin on the function and morphology of cultured hamster Kupffer cells

text: The mechanisms of hepatic reticuloendothelial cell dysfunction in obstructive jaundice were investigated using cultured hamster Kupffer cells. The introduction of free bile acids, cholic acid (CA) at concentrations over 2 mM and chenodeoxycholic acid (CDCA) over 1 mM inhibited colloidal carbon pinocytosis. CA and CDCA at concentrations over 0.5 mM inhibited IgG-coated sheep red blood cell phagocytosis. With the application of conjugated bile acid and endotoxin at concentrations over 50 μg/ml, endocytic function was inhibited. With bile acids, a dose-dependent increase in the concentration of β-glucuronidase occurred in the culture medium, and with endotoxin a timedependent increase in β-glucuronidase was noted. Bile acids produced alterations in cell organelles before destruction of the cell membrane. The presence of endotoxin led to the appearance of large vacuoles in the cytoplasm. These observations suggest that bile acids and endotoxin inhibit Kupffer cells by different mechanisms. We tentatively conclude that bile acids rather than endotoxin influence Kupffer cells in vivo.


title: Multiagent imaging of inflammation and infection with radionuclides

text: Molecular imaging with single photon- and positron-emitting tracers plays an important role in the evaluation of inflammation and infection. Although supplanted by labeled leukocyte imaging for most indications, gallium-67 remains useful for opportunistic infections, pulmonary inflammation and interstitial nephritis and, when [(18)F]FDG is not available, spinal infection and fever of unknown origin. In vitro labeled leukocyte imaging is the radionuclide procedure of choice for most infections in immunocompetent patients. When performed for musculoskeletal infection, complementary bone marrow imaging usually is necessary. Recent data suggest that dual time point imaging might be an alternative to marrow imaging. Several methods of labeling leukocytes in vivo, with agents including antigranulocyte antibodies and antibody fragments, peptides and cytokines, have been investigated, with variable results. These agents are not widely available and none of them are available in the USA. Radiolabeled antibiotics have been investigated as “infection-specific” tracers, but the results to date have been disappointing. Conversely, radiolabeled antimicrobial peptides do hold promise as infection-specific tracers. The use of positron-emitting tracers for diagnosing inflammation and infection has generated considerable interest. [(18)F]FDG is useful in fever of unknown origin, spinal osteomyelitis, vasculitis and sarcoidosis. Other positron-emitting tracers that have been investigated include [(18)F]FDG-labeled leukocytes, copper-64-labeled leukocytes, gallium-68 citrate and iodine-124 FIAU. Although radiolabeled tracers are used primarily for diagnosis, they also offer objective biomarkers for assessing response to therapeutic interventions in inflammatory diseases. They could also potentially be used to target cells and molecules with specific receptor expression for histological characterization, select patients for receptor-targeted therapy and predict response to treatment.


title: Severe juvenile dermatomyositis: two patients complicated with extra musculocutaneous involvement

text: Here we report two patients with severe juvenile dermatomyositis (JDM) complicated with extra musculocutaneous involvement. The first case (a 10-year-old boy) had unusual initial presentation of JDM complicated with interstitial lung disease documented with high-resolution computed tomography. He had a rapidly progressive course and died in 7 weeks after the onset of the disease despite steroid and immunosuppressive treatment. The second case (a 14-year-old boy) was presented with myositis complicated with hepatitis. He also had a chronic course of JDM with unfavorable outcome. It appears that the prognosis of patients with severe JDM is related with the degree of autoimmune vasculitis on extra musculocutaneous involvement.


title: A retrospective cohort study examining the association between body mass index and mortality in severe sepsis

text: Body mass index (BMI) is an easily calculated indicator of a patient’s body mass including muscle mass and body fat percentage and is used to classify patients as underweight or obese. This study is to determine if BMI extremes are associated with increased 28-day mortality and hospital length of stay (LOS) in emergency department (ED) patients presenting with severe sepsis. We performed a retrospective chart review at an urban, level I trauma center of adults admitted with severe sepsis between 1/2005 and 10/2007, and collected socio-demographic variables, comorbidities, initial and most severe vital signs, laboratory values, and infection sources. The primary outcome variables were mortality and LOS. We performed bivariable analysis, logistic regression and restricted cubic spline regression to determine the association between BMI, mortality, and LOS. Amongst 1,191 severe sepsis patients (median age, 57 years; male, 54.7 %; median BMI, 25.1 kg/m(2)), 28-day mortality was 19.9 % (95 % CI 17.8–22.4) and 60-day mortality was 24.4 % (95 % CI 21.5–26.5). Obese and morbidly obese patients were younger, less severely ill, and more likely to have soft tissue infections. There was no difference in adjusted mortality for underweight patients compared to the normal weight comparator (OR 0.74; CI 0.42–1.39; p = 0.38). The obese and morbidly obese experienced decreased mortality risk, vs. normal BMI; however, after adjustment for baseline characteristics, this was no longer significant (OR 0.66; CI 0.42–1.03; p = 0.06). There was no significant difference in LOS across BMI groups. Neither LOS nor adjusted 28-day mortality was significantly increased or decreased in underweight or obese patients with severe sepsis. Morbidly obese patients may have decreased 28-day mortality, partially due to differences in initial presentation and source of infection. Larger, prospective studies are needed to validate these findings related to BMI extremes in patients with severe sepsis.


title: Prediction of Survival After Liver Transplantation for Chronic Severe Hepatitis B Based on Preoperative Prognostic Scores: A Single Center’s Experience in China

text: BACKGROUND: The aim of this study was to estimate the utility of a preoperative model of end-stage liver disease (MELD) score and Child-Turcotte-Pugh (CTP) score in predicting the prognosis after othotopic liver transplantation (OLT) for chronic severe hepatitis B (CSHB) and explore the prognostic factors. METHODS: The outcome of 137 patients who underwent OLT using donors after cardiac death (DCDs) for CSHB in our center was reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method; the log-rank test was used for univariate analysis; and the Cox proportional hazards regression model was used for prognostic factors screening. RESULTS: The overall mortality rate was 33.6% (46/137); and 1-month, 6-month, 1-year, and 5-year patient survival rates were 75.8, 72.0, 71.0, and 60.1%, respectively. Most patients (33/46) died during the first month after OLT. The area under the curve values generated by the receiver operating characteristics curves were 0.82 [95% confidence interval (CI) 0.72–0.92] and 0.68 (95% CI 0.58–0.79), respectively (P < 0.01), for the MELD and CTP models in predicting 1-month mortality after OLT. Patients with a preoperative MELD score <33.8 or a CTP score <12.5 had significantly better prognosis than those with higher scores (P < 0.05). Other mortality predictors include hepatic encephalopathy, preoperative infection, serum creatinine ≥1.5 mg/dl. CONCLUSIONS: The MELD score was more efficient than the CTP score for evaluating the short-term prognosis in patients with CSHB undergoing OLT using DCDs, which should be taken into consideration during graft allocation.


docid: cgcuzxdt

title: The Race to Zero?: China's Poaching of Taiwan's Diplomatic Allies

text: The election of Tsai Ing-wen as President of the Republic of China (Taiwan) in 2016 reignited Beijing's quest to poach Taiwan's diplomatic allies. Between her election in January 2016 and reelection in January 2020, Taiwan has lost seven countries to China. After eight years of a “diplomatic truce” under President Ma Ying-jeou, China re-started its multi-pronged strategy to pressure Taiwan into eventual unification, and one of the key tactics is to poach all of Taiwan's now-15 remaining diplomatic allies to eliminate its international legitimacy. This article seeks to explain what, if any, benefits formal diplomatic relations provide Taiwan and the ways in which Beijing induces countries to switch ties. It concludes by providing recommendations for what actions the United States can undertake to slow the impending completion of the “race to zero.”


Severe Cellular Immunodeficiency Triggered by the CDK4/6 Inhibitor Palbociclib


Clinical spectrum of the Middle East respiratory syndrome coronavirus (MERS-CoV)


title: Respiratory muscle ultrasonography: methodology, basic and advanced principles and clinical applications in ICU and ED patients—a narrative review

text: Respiratory muscle ultrasound is used to evaluate the anatomy and function of the respiratory muscle pump. It is a safe, repeatable, accurate, and non-invasive bedside technique that can be successfully applied in different settings, including general intensive care and the emergency department. Mastery of this technique allows the intensivist to rapidly diagnose and assess respiratory muscle dysfunction in critically ill patients and in patients with unexplained dyspnea. Furthermore, it can be used to assess patient–ventilator interaction and weaning failure in critically ill patients. This paper provides an overview of the basic and advanced principles underlying respiratory muscle ultrasound with an emphasis on the diaphragm. We review different ultrasound techniques useful for monitoring of the respiratory muscle pump and possible therapeutic consequences. Ideally, respiratory muscle ultrasound is used in conjunction with other components of critical care ultrasound to obtain a comprehensive evaluation of the critically ill patient. We propose the ABCDE-ultrasound approach, a systematic ultrasound evaluation of the heart, lungs and respiratory muscle pump, in patients with weaning failure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05892-8) contains supplementary material, which is available to authorized users.


title: Lung–kidney interactions in critically ill patients: consensus report of the Acute Disease Quality Initiative (ADQI) 21 Workgroup

text: BACKGROUND: Multi-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO). METHODS: A consensus conference on the spectrum of lung–kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function. CONCLUSION: The ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung–kidney interactions to improve care processes and outcomes in critical illness. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05869-7) contains supplementary material, which is available to authorized users.


September 10-14 Munich, Germany CIRSE 2011


EANM'17


October 2-6 Valencia, Spain CIRSE 2010


CIRSE 2012 ABSTRACTS & AUTHOR INDEX: September 15-19 Lisbon, Portugal


International Surgical Week ISW 2011: Yokohama, Japan, August 28–September 1, 2011


title: Thoracic imaging with (67)gallium

text: In the past, gallium-67 imaging has undergone several ups and downs related to its clinical importance. After a period of initial enthusiasm, its role and indications are now established. At present, there are two fields of clinical interest for (67)Ga-imaging: (1) mediastinal staging in bronchogenic carcinoma and the staging of malignant lymphoma; (2) assessment of activity in interstitial lung diseases, especially sarcoidosis and inflammatory lung disorders. The advantage of (67)Ga-imaging is that it is highly sensitive for the detection of neoplastic and inflammatory processes, independent of anatomical barriers. Particularly with the challenge of AIDS, (67)Ga-imaging will gain increasing importance in the future. The low specificity of gallium for detecting underlying disorders precludes its use as a primary diagnostic tool. Therefore, and because of the cost and radiation load, the indications for application will have to be selected very carefully.


CIRSE 2017


CIRSE 2008


CIRSE 2015


EANM’16


title: Parasites of the Giant Panda: A Risk Factor in the Conservation of a Species

text: The giant panda, with an estimated population size of 2239 in the world (in 2015), is a global symbol of wildlife conservation that is threatened by habitat loss, poor reproduction and limited resistance to some infectious diseases. Of these factors, some diseases caused by parasites are considered as the foremost threat to its conservation. However, there is surprisingly little published information on the parasites of the giant panda, most of which has been disseminated in the Chinese literature. Herein, we review all peer-reviewed publications (in English or Chinese language) and governmental documents for information on parasites of the giant pandas, with an emphasis on the intestinal nematode Baylisascaris schroederi (McIntosh, 1939) as it dominates published literature. The purpose of this chapter is to: (i) review the parasites recorded in the giant panda and describe what is known about their biology; (ii) discuss key aspects of the pathogenesis, diagnosis, treatment and control of key parasites that are reported to cause clinical problems and (iii) conclude by making some suggestions for future research. This chapter shows that we are only just ‘scratching the surface’ when it comes to parasites and parasitological research of the giant panda. Clearly, there needs to be a concerted research effort to support the conservation of this iconic species.


title: Canine and feline pregnancy loss due to viral and non-infectious causes: A review

text: Among the causes for pregnancy loss, viruses and non-infectious factors are among the most important. In both dogs and cats, research and clinical evidence provide proof that there is an increasing incidence of pregnancy loss associated with infectious diseases like herpesvirus, as well as the presence of toxicants or chemicals in the animal's diet and environment. Endocrine causes must be taken into consideration when dealing with pregnancy loss. This review will cover the most recent knowledge regarding viral and non-infectious of pregnancy losses in the dog and cat.


title: Reproductive emergencies in camelids

text: Emergencies in theriogenology practice go beyond just saving the life of the patient, but also preserving its reproductive abilities. Camelid emergency medicine is a relatively new field. This paper discusses the most common reproductive emergencies, their diagnosis, treatment, and prognosis in male and female camelids. The conclusions drawn are based primarily on clinical observations by the authors over the last 25 years. Special consideration is given to peculiarities of the species, particularly in the choice of obstetrical manipulations and therapies.


title: Infectious causes of embryonic and fetal mortality

text: The purpose of this review is to summarize bacterial, fungal, protozoan, and viral causes of reproductive dysgenesis in cattle, sheep, goats, pigs, horses, dogs, and cats. The clinical presentations of disease due to reproductive pathogens are emphasized, with a focus on assisting development of complete lists of causes that result in abortion and infertility in these species. Clinicians are encouraged to assess clinical presentation, create complete lists of differential diagnoses, obtain appropriate diagnostic samples, maximize diagnostic laboratory support, and avoid zoonotic infections resulting from reproductive pathogens of animals. The foundation of an accurate diagnosis of reproductive loss due to infectious pathogens facilitates the prudent use of immunization and biosecurity to minimize reproductive losses.


CIRSE 2018


Abstracts of the 4(th) Central European Congress of Intensive Care Medicine – CECIM 2008 – 140(th) Anniversary of Novel Laureate Dr. Karl Landsteiner, October 24-25, 2008, Baden, Austria


Postgraduate Educational Programme


ECR 2000 Book of Abstracts - Pt. 3 - Author’s Index


docid: btcdjmfp

title: Key Note and State of the Art Lectures


title: Decitabine: a historical review of the development of an epigenetic drug

text: The development of decitabine from its synthesis in 1964 to the submission of a registration file has been described. Although the unique DNA-demethylating capacity of decitabine is known for a long time, its application is under continuing investigation. The use of decitabine in MDS, AML, CML, stem cell transplant, sickle cell anemia and thalassemia looks promising. The epigenetic dose seems lower than the cytotoxic dose. Whereas most drugs have matured after 40 years, decitabine is only at the beginning of a new development phase in epigenesis.


title: Length of encapsidated cargo impacts stability and structure of in vitro assembled alphavirus core-like particles

text: In vitro assembly of alphavirus nucleocapsid cores, called core-like particles (CLPs), requires a polyanionic cargo. There are no sequence or structure requirements to encapsidate single-stranded nucleic acid cargo. In this work, we wanted to determine how the length of the cargo impacts the stability and structure of the assembled CLPs. We hypothesized that cargo neutralizes the basic region of the alphavirus capsid protein and if the cargo is long enough, it will also act to scaffold the CP monomers together. Experimentally we found that CLPs encapsidating short 27mer oligonucleotides were less stable than CLPs encapsidating 48mer or 90mer oligonucleotides under different chemical and thermal conditions. Furthermore, cryo-EM studies showed there were structural differences between CLPs assembled with 27mer and 48mer cargo. To mimic the role of the cargo in CLP assembly we made a mutant (4D) where we substituted a cluster of four Lys residues in the CP with four Asp residues. We found that these few amino acid substitutions were enough to initiate CLP assembly in the absence of cargo. The cargo-free 4D CLPs show higher resistance to ionic strength and increased temperature compared to wild-type cargo containing CLPs suggesting their CLP assembly mechanism might also be different.


docid: qwsznfad

title: Abstracts: 31(st)European Congress of Pathology


Abstracts DGRh-Kongress 2013


Intensivmedizin und Notfallmedizin : 6. Deutscher Interdisziplinärer Kongress für Intensivmedizin und Notfallmedizin, 13. bis 16. November 2002 in Hamburg¶A. Althoff, D. Walmrath, W. Seeger


docid: jjzparqy

title: Scientific Sessions (SS): Thursday


ECR 2000 Book of Abstracts - Pt. 1 - Scientific Programme


Abstracts from the 37th Congress of the Société Internationale d’Urologie, Centro de Congressos de Lisboa, October 19-22, 2017


Poster


docid: eaqkadyy

title: 2009 Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Phoenix, Arizona, USA, 22–25 April 2009: Poster presentations


title: Interstitielle Lungenkrankheiten

text: Interstitial lung diseases comprise a heterogeneous group of about 200 entities. In the classification of these diseases, diffuse parenchymal lung diseases with known cause, granulomatous diseases, and other specific interstitial lung diseases are separated from the important group of idiopathic interstitial pneumonias, which are classified according to the 2002 ATS/ERS consensus classification. Concerning the histological pattern, this classification differentiates between “usual interstitial pneumonia” (UIP), “nonspecific interstitial pneumonia” (NSIP), “organising pneumonia” (COP), “diffuse alveolar damage” (DAD), “respiratory bronchiolitis” (RB), “desquamative interstitial pneumonia” (DIP), “lymphocytic interstitial pneumonia” (LIP) and “unclassifiable interstitial pneumonias”. A key message of this classification is that the pathologist will give the diagnosis of a histological pattern, whereas the final clinicopathologic diagnosis can be made only by the clinical pulmonologist after careful correlation with the clinical and radiologic features, which is essential in the diagnosis of interstitial lung diseases.


ECR 1991 Book of Abstracts - Pt. 2 - Scientific Exhibition, Informatique


CIRSE 2019 Abstracts


title: Aerosols for systemic treatment

text: The development of a new group of drugs (polypeptides) have recently increased the interest of alternative administration to the enteral route because of its proteolytic activity and the catabolism of the “first-pass effect.” Aside from the “needle,” the administration in the respiratory tract via aerosol is the method with the best efficiency. But several problems prohibited its spreading: (1) the accuracy and the reproducibility of the inhaled dose (range ca. 1:4); (2) the small amount of inhaled drug in relation to the dose in the aerosol delivery system (range ca. 1%–10%); (3) the fear of allergic reactions of the respiratory system; (4) the variability of the drug transport into the systemic circulation. New approaches and data raise hopes in reducing the problems: (1) aerosol delivery systems with defined particle spectrum and storage systems; slow vital capacity inhaling maneuver; (2) delivery systems that nebulizes nearly the total amount of drug; (3) all studies with the inhalation application of insulin, heparin, ergotamin, ribavirin, aminoglycosides, and “cigarette smoke” do not reveal any relevant allergic reaction; (4) many studies were performed in the last 10 years on the influence of substances and especially of diseases on the transport of molecules through the respiratory tract. Only a few of them are relevant (exogen allergic alveolitis, active sarcoidosis, active smoking). Aerosols for systemic drug treatment seems to be a gained alternative to the “syringe.”


ECR 2001 Book of Abstracts - A - Postgraduate Educational Programme


ECR 1997 Book of Abstracts - Pt. 1 - Scientific Programme


title: Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies: Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

text: The risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during that time, but above all, the risk of infection is determined by the selected transplantation modality (e.g. HLA-match between the stem cell donor and recipient, T cell depletion of the graft, and others). In comparison with patients treated with high-dose chemotherapy and autologous stem cell transplantation, patients undergoing allogeneic stem cell transplantation are at a much higher risk of infection even after hematopoietic reconstitution, due to the delayed recovery of T and B cell functions. The rate at which immune function recovers after hematopoietic reconstitution greatly influences the incidence and type of post-transplant infectious complications. Infection-associated mortality, for example, is significantly higher following engraftment than during the short neutropenic period that immediately follows transplantation.


title: Assembly/disassembly of a complex icosahedral virus to incorporate heterologous nucleic acids

text: Hollow protein containers are widespread in nature, and include virus capsids as well as eukaryotic and bacterial complexes. Protein cages are studied extensively for applications in nanotechnology, nanomedicine and materials science. Their inner and outer surfaces can be modified chemically or genetically, and the internal cavity can be used to template, store and/or arrange molecular cargos. Virus capsids and virus-like particles (VLP, noninfectious particles) provide versatile platforms for nanoscale bioengineering. Study of capsid protein self-assembly into monodispersed particles, and of VLP structure and biophysics is necessary not only to understand natural processes, but also to infer how these platforms can be redesigned to furnish novel functional VLP. Here we address the assembly dynamics of infectious bursal disease virus (IBDV), a complex icosahedral virus. IBDV has a ~70 nm-diameter T = 13 capsid with VP2 trimers as the only structural subunits. During capsid assembly, VP2 is synthesized as a precursor (pVP2) whose C terminus is cleaved. The pVP2 C terminus has an amphipathic helix that controls VP2 polymorphism. In the absence of the VP3 scaffolding protein, necessary for control of assembly, 466/456-residue pVP2 intermediates bearing this helix assemble into VLP only when expressed with an N-terminal His(6) tag (the HT-VP2-466 protein). HT-VP2-466 capsids are optimal for genetic insertion of proteins (cargo space ~78 000 nm(3)). We established an in vitro assembly/disassembly system of HT-VP2-466-based VLP for heterologous nucleic acid packaging and/or encapsulation of drugs and other molecules. HT-VP2-466 (empty) capsids were disassembled and reassembled by dialysis against low-salt/basic pH and high-salt/acid pH buffers, respectively, thus illustrating the reversibility in vitro of IBDV capsid assembly. HT-VP2-466 VLP also packed heterologous DNA by non-specific confinement during assembly. These and previous results establish the bases for biotechnological applications based on the IBDV capsid and its ability to incorporate exogenous proteins and nucleic acids.


ESP Abstracts 2015


EAORL Abstract Supplement: 4th EHNS Athens 4–6 March 2010


ECR 1991 Book of Abstracts - Pt. 1 - Scientific Programme


Second Meeting of West European Societies of Biological Psychiatry Psychiatric Challenges throughout the Life Span 13–15 December 2007 – Strasbourg, France


Scientific Sessions (SS): Wednesday


27th International Congress of the European Association for Endoscopic Surgery (EAES) Sevilla, Spain, 12–15 June 2019


title: Influenza H1N1 infection in a patient with psoriatic arthritis in treatment with Adalimumab: a case report

text: In March 2009 was the beginning of an epidemic flue caused by avian influenza A virus H1N1. The disease varies from mild to serious and fatal cases. There are many hypotheses explaining why this virus infection would be fatal. One of these is the impaired immune response of the infected patient. The use of tumor necrosis factor-alpha inhibitors may cause decreased immune response and greater susceptibility to infections. We presented a case of a patient using adalimumab that have developed H1N1 without complications. This is the first case of H1N1 in a patient using adalimumab reported in Brazil. We discuss the possibility that anti-TNF may not predisposes to a serious form of the disease or fatal complications.


Honorary Lectures Categorical Courses Refresher Courses Workshops State-of-the-Art Symposia: Friday


Posters


Oral Free Paper Sessions


Scientific Session of the 16th World Congress of Endoscopic Surgery, Jointly Hosted by Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) & Canadian Association of General Surgeons (CAGS), Seattle, Washington, USA, 11–14 April 2018: Poster Abstracts


Frühjahrstagung 2007 der Österreichischen Gesellschaft für Hämatologie und Onkologie


19th Meeting of the Austrian Society of Transplantation, Transfusion, and Genetics, October 26–28, 2005


46th Annual Meeting of the Austrian Society of Surgery, Vienna, May 26–28, 2005


title: Functionalized magnetic microparticle-based colorimetric platform for influenza A virus detection

text: A colorimetric platform for influenza A virus detection was developed by using the high efficiency of enzymatic catalysis and the reduction of gold ions with hydrogen peroxide. Aptamer-functionalized magnetic microparticles were synthesized to capture the influenza A virus. This was followed by the binding of ConA-GOx-AuNPs to the H3N2 virus through the ConA-glycan interaction. The sandwich complex was subsequently dispersed in glucose solution to trigger an enzymatic reaction to produce hydrogen peroxide, which controlled the growth of gold nanoparticles and produced colored solutions. The determination of H3N2 concentration was realized by comparing the two differently colored gold nanoparticles. This method could detect the target virus as low as 11.16 μg ml(−1). Furthermore, it opens new opportunities for sensitive and colorimetric detection of viruses and proteins.


ECR 2001 Book of Abstracts - B - Scientific Sessions


40th Annual Meeting of the GTH (Gesellschaft für Thrombose- und Hämostaseforschung)


Scientific Exhibition


ITS ASM 2012


Proceedings of the World Molecular Imaging Congress 2019, Montreal Quebec, Canada September 4-7, 2019: Late-Breaking Abstracts


National scientific medical meeting 1995 abstracts: Oral presentations


title: Clinical Aspects of Upper and Lower Respiratory Tract Infections

text: Respiratory tract infections are among the most common illnesses leading to medical consultation, and are associated with significant mortality. Community-acquired pneumonia is a common illness and, while Streptococcus pneumoniae continues to be the most frequent causative agent, atypical pathogens such as Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella species are now identified as additional common aetiological agents. Since clinical and roentgenographic features poorly predict the aetiological agent in most cases of community-acquired pneumonia, empirical therapy is generally recommended. Nosocomial pneumonia is the second most common hospital-acquired infection and is associated with significant mortality. Aerobic Gram-negative bacilli and Staphylococcus aureus are the predominant causative pathogens. New techniques to improve the diagnosis of nosocomial pneumonia have been introduced, but their role has not been entirely clarified. Therapy directed toward the most likely pathogens (aerobic Gram-negative species and S. aureus) on an empirical basis is recommended until more specific information is obtained. Acute exacerbations of chronic bronchitis should be treated with antimicrobial therapy directed toward S. pneumoniae, Haemophilus influenzae or Moraxella catarrhalis. Because of the emergence of β-lactamase-producing strains of H. influenzae and M. catarrhalis, the choice of an antimicrobial agent has to be carefully considered. Group A β-haemolytic streptococci are the most common cause of bacterial pharyngitis and penicillin remains the drug of choice. Patients suffering from otitis media and sinusitis are infected with the same organisms as those patients with acute exacerbations of chronic bronchitis and antibacterial choices are therefore similar.


3rd International Congress “Sepsis and Multiorgan Dysfunction”: September 5–8, 2007 Weimar


Neurocritical Care Society 12(th) Annual Meeting


Abstracts 7th international congress “sepsis and multiorgan dysfunction”


Neurocritical Care Society 7th Annual Meeting


Abstracts Presented at the Neurocritical Care Society (NCS) 15th Annual Meeting


Proceedings of the 2009 World Molecular Imaging Congress Montreal, Canada, September 23–26


Proceedings of the RAMI Intern Section Meeting, 18th January 2014


9th International Congress “Sepsis and Multiorgan Dysfunction”


Abstract Book: Society of Surgical Oncology 69(th) Annual Cancer Symposium


title: The Place of Macrolides in the Treatment of Upper Respiratory Tract Infections

text: The majority of all acute upper respiratory tract infections (URTIs) are viral in aetiology. Bacterial infection, either as a prime cause or secondary to the initial viral infection, can be effectively eradicated with appropriate drug therapy. A course of penicillin is usually effective in cases of acute tonsillitis, pharyngitis, otitis media and sinusitis. Macrolide antibiotics may be prescribed as an alternative, especially if β-lactamase-producing strains are present. Roxithromycin achieves high tissue concentrations, and cure rates between 85 and 100% have been reported in various URTIs.


Neurocritical Care Society 14(th) Annual Meeting


docid: otpxoqvk

title: Proceedings of the World Molecular Imaging Congress 2016, New York, New York, September 7-10, 2016: General Abstracts


Irish Thoracic Society Annual Scientific Meeting: 21(st), 22(nd)and 23(rd)November 2019 – The Galmont Hotel, Galway


Neurocritical Care Society 10th Annual Meeting: October 4 - 7, 2012 Sheraton Denver Downtown Hotel Denver, Colorado


title: The incidence and aetiology of respiratory tract infections in general practice — with emphasis onMycoplasma pneumoniae

text: The incidence of respiratory tract infections in patients seeking medical advice at a community care centre (Dalby) during 1973 and 1974 was studied. About every third patient seen at this primary health station presented with signs of such infections. In the age groups <10, 10–19, 20–39, 40–59 and ≥60 years, respiratory tract infections accounted for 65, 45, 32, 18 and 9% of the total number of diagnoses made during 1974. The aetiology of acute respiratory tract infections in a series of patients seen at this health station was studied. The series included randomly selected cases, but excluded children under seven years of age and patients presenting with signs of acute otitis media and tonsillitis. Attempts to establish the aetiology were made on the basis of the history, the clinical examination, and cultures for beta-haemolytic streptococci andMycoplasma pneumoniae, complement fixation tests for influenza A and B, para-influenza 1, 2, and 3, adeno, cytomegalovirus and respiratory syncytial virus, andChlamydia psittaci. Paul-Bunnell test and tests for cold agglutinins were also performed. With this test battery, an aetiological diagnosis was obtained in only 33% of the 101 patients studied. The findings suggest an infection withM. pneumoniae in 16%, with beta-haemolytic streptococci in 9%, and with viruses (adeno and para-influenza) in 7% of the patients. The present communication highlights the role ofM. pneumoniae in upper respiratory infections, as few data have appeared on such infections in patients seen in general practice. The difficulty of establishing the aetiology of respiratory tract infections and the consequent treatment dilemma is discussed.


Royal Academy of Medicine in Ireland


ESID 2014 ORAL PRESENTATIONS


Abstracts 4th International Congress “Sepsis and Multiorgan Dysfunction”: September 9–12, 2009 Weimar


RAMI Section of Biomedical Sciences: Annual Meeting 2012


Medical care for refugees: A question of ethics and public health


title: Legal Concerns in Psychosomatic Medicine

text: In the practice of psychosomatic medicine, psychiatrists frequently encounter issues of legal concern. This article provides an overview of legal topics frequently encountered by the psychiatric consultant. One such area, discussed first in this article, is confidentiality and the management of private patient information. A second common interface between law and psychiatry is in the area of medical decision making. The psychiatric consultant is often asked to evaluate a patient's ability to accept or refuse treatment, and then make a determination of capacity. When the patient cannot give informed consent, an alternate decision maker must be found. Finally, malpractice liability is often a concern for the psychiatric consultant. Overall, psychiatrists should approach the care of patients foremost from a clinical perspective, while understanding the applicable laws and regulations of the jurisdictions in which they practice. In addition, clinicians should be aware of the legal and risk management resources available to them should a complex situation arise.


Irish Thoracic Society Annual Scientific Meeting, Ramada Hotel, Belfast: 7th–8th November 2008


National common metrics for the NIH Clinical and Translational Science Award Institutions: A signal of the transformation of the American biomedical research enterprise


Development of a SARS vaccine: an industrial perspective on the global race against a global disease


title: Chloroquine-containing compounds: a patent review (2010 – 2014)

text: Introduction: Chloroquine (CQ) has been well known for its antimalarial effects since World War II. However, it is gradually being phased out from clinical use against malaria due to emergence of CQ-resistant Plasmodium falciparum strains. Besides low cost and tolerability, ongoing research has revealed interesting biochemical properties of CQ that have inspired its repurposing/repositioning in the management of various infectious/noninfectious diseases. Consequently, several novel compounds and compositions based on its scaffold have been studied and patented. Areas covered: In this review, patents describing CQ and its derivatives/compositions over the last 5 years are analyzed. The review highlights the rationale, chemical structures, biological evaluation and potential therapeutic application of CQ, its derivatives and compositions. Expert opinion: Repurposing efforts have dominantly focused on racemic CQ with no studies exploring the effect of the (R) and (S) enantiomers, which might potentially have additional benefits in other diseases. Additionally, evaluating other similarly acting antimalarials in clinical use and structural analogs could help maximize the intrinsic value of the 4-aminoquinolines. With regard to cancer therapy, successful repurposing of CQ-containing compounds will require linking the mode of action of these antimalarials with the signaling pathways that drive cancer cell proliferation to facilitate the development of a 4-amino-7-chloroquinoline that can be used as a synergistic partner in anticancer combination chemotherapy.


title: Virus-like particle vaccines: immunology and formulation for clinical translation

text: Introduction: Virus-like particle (VLP) vaccines face significant challenges in their translation from laboratory models, to routine clinical administration. While some VLP vaccines thrive and are readily adopted into the vaccination schedule, others are restrained by regulatory obstacles, proprietary limitations, or finding their niche amongst the crowded vaccine market. Often the necessity to supplant an existing vaccination regimen possesses an immediate obstacle for the development of a VLP vaccine, despite any preclinical advantages identified over the competition. Novelty, adaptability and formulation compatibility may prove invaluable in helping place VLP vaccines at the forefront of vaccination technology. Areas covered: The purpose of this review is to outline the diversity of VLP vaccines, VLP-specific immune responses, and to explore how modern formulation and delivery techniques can enhance the clinical relevance and overall success of VLP vaccines. Expert commentary: The role of formation science, with an emphasis on the diversity of immune responses induced by VLP, is underrepresented amongst clinical trials for VLP vaccines. Harnessing such diversity, particularly through the use of combinations of select excipients and adjuvants, will be paramount in the development of VLP vaccines.


The predictive value of FiO2 for outcome of children with respiratory syncytial virus-induced acute respiratory distress syndrome


title: Transfusion massive et coagulopathie-: physiopathologie et implications cliniques

text: PURPOSE: To review the pathophysiology of coagulopathy in massively transfused, adult and previously hemostatically competent patients in both elective surgical and trauma settings, and to recommend the most appropriate treatment strategies. METHODS: Medline was searched for articles on “massive transfusion,” “transfusion,” “trauma,” “surgery,” “coagulopathy” and “hemostatic defects.” A group of experts reviewed the findings. PRINCIPAL FINDINGS: Coagulopathy will result from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. The clinical significance of the effects of hydroxyethyl starch solutions on hemostasis remains unclear. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Red cells play an important role in coagulation and hematocrits higher than 30% may be required to sustain hemostasis. In elective surgery patients, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. In trauma patients, tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. The use of platelets and/or fresh frozen plasma should depend on clinical judgment as well as the results of coagulation testing and should be used mainly to treat a clinical coagulopathy. CONCLUSIONS: Coagulopathy associated with massive transfusion remains an important clinical problem. It is an intricate, multifactorial and multicellular event. Treatment strategies include the maintenance of adequate tissue perfusion, the correction of hypothermia and anemia, and the use of hemostatic blood products to correct microvascular bleeding. OBJECTIF: Revoir la physiopathologie de la coagulopathie chez les adultes transfusés massivement et auparavant compétents sur le plan hémostatique, à la fois dans le contexte ďune intervention chirurgicale réglée ou à la suite ďun traumatisme. Recommander les stratégies thérapeutiques les plus appropriées. MÉTHODE: Dans Medline, nous avons cherché les articles traitant de “massive transfusion,” “transfusion,” “trauma,” “surgery,”“coagulopathy” et “hemostatic defects.” Un groupe ďexperts a examiné les résultats. CONSTATATIONS PRINCIPALES: La coagulopathie résulte de ľhémodilution, ľhypothermie, ľusage de produits sanguins fractionnés et la coagulation intravasculaire disséminée. La portée clinique des effets des solutions ďhydroxyéthyl-amidon sur ľhémostase n’est toujours pas claire. Le maintien ďune température corporelle normale est une stratégie de première intention efficace pour améliorer ľhémostase pendant la transfusion massive. Les globules rouges sont importants dans la coagulation et des hématocrites supérieurs è 30 % pourraient être nécessaires à une hémostase adéquate. Chez les patients en chirurgie réglée, une baisse de la concentration de fibrinogène est observée précocement tandis que la thrombocytopénie est plus tardive. Chez les traumatisés, le trauma tissulaire, le choc, ľanoxie et ľhypothermie tissulaires contribuent au développement ďune coagulation intravasculaire disséminée et du saignement microvasculaire. Ľutilisation de plaquettes et/ou de plasma frais congelé dépendra du jugement du clinicien ainsi que des résultats des tests de coagulation. La transfusion devra surtout viser le traitement ďune coagulopathie clinique (saignement microvasculaire). CONCLUSION: La coagulopathie associée à la transfusion massive demeure un important problème clinique. C’est un événement complexe, multifactoriel et multicellulaire. Le traitement comprend le maintien ďune perfusion tissulaire adéquate, la correction de ľhypothermie et de ľanémie et ľusage de produits sanguins hémo-statiques pour corriger le saignement microvasculaire.


Abstracts of the 26th Annual Conference of APASL, February 15–19, 2017, Shanghai, China


Critical Care Canada Forum 2019 Abstracts


CCCF 2017 Abstracts


Indian Society of Gastroenterology


Critical Care Canada Forum 2018 Abstracts


Gemeinsam erfolgreich: Pädiatrie & Pädologie und der Pädiatrische Frühling


Send in the therapists?


docid: apcueljv

title: Mental health care for international Chinese students affected by the COVID-19 outbreak


Abstracts of the 27th Annual Conference of APASL, March 14–18, 2018, New Delhi, India


Call for Paper


title: And Why So Great a “No?”: The Donor and Academic Communities' Failure to Confront Global Chronic Disease

text: Chronic diseases are the dominant issues for global public health in terms of mortality, morbidity, and cost, and they have been identified as such for >40 years. Despite their predominance, however, these diseases—cardiovascular disease (CVD), diabetes, cancer, pulmonary disease, mental health, and dementia—attract little attention in the public health curriculum and even less from the funding community. We explore the rationales that have perpetuated this inability or unwillingness to match need with effort. We examine 3 concepts that impede changing this relationship: 1) the traditional contextual view of public health that emerged, to be sure with great success, in the post–World War II era; 2) the failure of public health to transition to economic development as the goal of health assistance; and 3) the unwillingness of public health to confront social, political, and economic policies as the foci of upstream drivers of the public's health. We conclude with a discussion of the need for public health to expand its horizon and tear down the walls of the silos that inhibit the emergence of relevant global public health.


title: New method of preparation of carboxy-protected amino acid conjugates of glycyrrhizinic acid

text: A method for preparation of carboxy-protected amino acid conjugates of glycyrrhizinic acid with the use of N-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, and methyl esters of L-amino acids (phenylalanine, tyrosine, leucine, isoleucine, and methionine) in 85–90% yield was developed. The structure of the prepared compounds was confirmed by IR and (13)C NMR spectra.


docid: pdvddowh

title: Synthesis of amino acid conjugates of glycyrrhizic acid using N-hydroxyphthalimide and N,N'-dicyclohexylcarbodiimide

text: Synthesis of amino acid conjugates of glycyrrhizic acid with the use of N-hydroxyphthalimide, N,N'-dicyclohexylcarbodiimide, and tert-butyl esters of L-amino acids (valine, isoleucine, phenylalanine, and methionine) was performed followed by deprotection with trifluoroacetic acid. The target amino acid conjugates were isolated by column chromatography on silica gel in 40–45% yield. The structure of the prepared compounds was confirmed by IR and (13)C NMR spectroscopy.


title: Infektionen bei immunkompromittierten Patienten

text: Patients with immunodeficiency and/or under immunosuppressive therapy have an increased risk of complications due to infectious diseases. After solid organ transplantation infections are the second most common cause of death. Prophylactic measures should therefore routinely be carried out. Infections in immunosuppressed patients may be associated with atypical clinical symptoms making the diagnosis and therapy a challenge for the treating physician. Viral and opportunistic infections in particular can be a therapeutic pitfall. A careful surveillance of the patient with respect to infectious diseases is essential in order to be able to make an early diagnosis and initiate appropriate measures.


docid: raikpuro

title: Emerging Zoonoses: Hantavirus-Infektionen

text: Among the emerging viruses, hantaviruses are being focused on more and more due to their increasing number and worldwide distribution. Transmission occurs via inhalation of aerosolized infected rodent excreta. The symptoms and course of disease vary with the infecting hantavirus species. The distribution of the different hantavirus species correlates with the geographical distribution of the virus-type-specific rodent host. Hantaviruses in Europe and Asia cause hemorrhagic fever with renal syndrome (HFRS). Infection with Puumala, the prevalent virus type in Germany, results in a more moderate form of HFRS, nephropathia epidemica. Infections with virus species on the American continents lead to a clinical picture with predominantly pulmonary pathology (hantaviral pulmonary syndrome). No specific antiviral therapy or approved vaccines are available for any hantavirus species. Controlling the rodent populations and avoiding contact with rodent excrement are the only measures that can be undertaken to contain and prevent infection.


COVID-19 and the consequences of isolating the elderly


title: Internationale kennisuitwisseling : Verslag van 16e symposium en vakbeurs ambulancezorg

text: Voor de 16e keer is onlangs het ambulancesymposium gehouden, dat ditmaal in het teken stond van veiligheid en ambulancezorg. Centrale vraag was: Wat kan de Nederlandse ambulancezorg leren van ambulancediensten in België, Engeland en Canada? Hoe wordt daar met veiligheid in de ambulancezorg omgegaan?


Mitteilungen der GARPS


docid: grqbsckl

title: Terugblik op de influenzapandemie

text: Influenza (‘griep’) is een acute luchtweginfectie, veroorzaakt door een influenzavirus. De infectie komt in Nederland vooral in koude jaargetijden voor. Verreweg de meeste patiënten herstellen binnen enkele weken, maar de infectie kan gepaard gaan met ernstige complicaties en bij sommigen fataal verlopen. In maart 2009 kwam de eerste melding van een nieuw influenza-A-virus (H1N1) uit Californië. Dit virus leek op een influenzavirus dat bij varkens voorkwam. Min of meer gelijktijdig kwamen er berichten uit Mexico over een forse toename van pneumonieën onder jonge mensen. Eind april bleek dat het Californische virus ook de oorzaak was van die Mexicaanse uitbraak. Op 24 april kwam de eerste pandemiewaarschuwing van de WHO. Het virus zou later genoemd worden naar de eerste vindplaats: Influenza A/California/7/2009 (H1N1)v, maar de termen ‘Mexicaanse griep’, ‘swine flu’ en ‘Nieuwe Influenza H1N1’ bleven internationaal in omloop. In dit artikel is gekozen voor de term Mexicaanse griep. De discrepantie tussen de uitgebreide voorbereiding en de uiteindelijke omvang van de pandemie heeft wereldwijd geleid tot behoefte aan evaluatie. Het lijkt te vroeg om nu al conclusies te trekken. De effectiviteit van preventieve zorg is altijd moeilijk te meten. Het resultaat van preventie is een non-event: als het goed wordt uitgevoerd, gebeurt er niets. De opvatting dat door de optimale voorbereiding en uitvoering van alle activiteiten de omvang van de pandemie is meegevallen, is niet populair. Duidelijk is al wel dat Europese afstemming node gemist is: op het terrein van voorbereiding, vaccinatie en antivirale behandeling waren er geen twee protocollen gelijk. Als alleen al dat zou verbeteren, is de evaluatie niet voor niets geweest.


Abstracts from USCAP 2020: Autopsy and Forensics (1-36)


Oral and Poster presentations


Abstracts from USCAP 2020: Medical Renal Pathology (1662-1696)


President’s Plenary Session


title: Surfactants: past, present and future

text: In 1929 Kurt von Neergaard performed experiments suggesting the presence of pulmonary surfactant and its relevance to the newborn's first breath. Almost 25 years later, Richard Pattle, John Clements and Chris Macklin, each working on the effects of nerve gases on the lungs, contributed to the understanding of the physiology of pulmonary surfactant. About 5 years later Mary Ellen Avery and Jere Mead published convincing evidence that preterm neonates dying of hyaline membrane disease (respiratory distress syndrome, RDS) had a deficiency of pulmonary surfactant. The first trials of nebulized synthetic (protein-free) surfactant to prevent RDS were published soon after Patrick Bouvier Kennedy (son of President John F Kennedy) died of this disorder after treatment in Boston. These trials were unsuccessful; however, Goran Enhorning and Bengt Robertson in the early 1970s demonstrated that natural surfactants (containing proteins) were effective in an immature rabbit model of RDS. Soon after this Forrest Adams showed that a natural surfactant was also effective in an immature lamb model. Working with him was Tetsuro Fujiwara who 2 years later, after returning to Japan, published the seminal article reporting the responses of 10 preterm infants with RDS to a bolus of modified bovine surfactant. During the 1980s there were numerous randomized controlled trials of many different natural and synthetic surfactants, demonstrating reductions in pulmonary air leaks and neonatal mortality. Subsequently natural surfactants were shown to be superior to the protein-free synthetic products. Recently there have been a number of randomized trials comparing different natural surfactant preparations. Commercially available bovine surfactants may have similar efficacy but there is some evidence that a porcine surfactant used to treat RDS with an initial dose of 200 mg per kg is more effective than a bovine surfactant used in an initial dose of 100 mg per kg. Bovine and porcine surfactants have not been compared in trials of prophylaxis. Very recently a new synthetic surfactant with a surfactant protein mimic has been compared with other commercially available natural and synthetic surfactants in two trials. The new surfactant may be superior to one of the older protein-free synthetic surfactants but there is no evidence of its superiority over established natural products and it is currently not approved for clinical use. A number of other new synthetic surfactants have been tested in animal models or in treatment of adults with ARDS, but so far there have been no reports of treatment of neonatal RDS. Natural surfactants work best if given by a rapid bolus into the lungs but less invasive methods such as a laryngeal mask, pharyngeal deposition or rapid extubation to CPAP have showed promise. Unfortunately, delivery of surfactant by nebulization has so far been ineffective. Surfactant treatment has been tried in a number of other neonatal respiratory disorders but only infants with meconium aspiration seem to benefit although larger and more frequent doses are probably needed to demonstrate improved lung function. A surfactant protocol based upon early treatment and CPAP is suggested for very preterm infants. Earlier treatment may improve survival rates for these infants; however, there is a risk of increasing the prevalence of milder forms of chronic lung disease. Nevertheless, surfactant therapy has been a major contribution to care of the preterm newborn during the past 25 years.


SRI 2020: Scientific Abstracts


title: Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS

text: Many different surfactant preparations derived from animal sources, as well as synthetic surfactants, are available for the treatment of preterm infants with respiratory distress syndrome (RDS). Natural, modified surfactants containing surfactant-associated proteins appear to be more effective than non-protein-containing synthetic surfactants. Comparative trials with poractant alfa at a higher initial dose of 200 mg/kg appear to be associated with rapid weaning of FiO(2), less need for additional doses, and decreased mortality in infants <32 weeks gestation when compared with beractant. Early rescue (<30 min of age) surfactant therapy is an effective method to minimize over treatment of some preterm infants who may not develop RDS. Surfactant therapy followed by rapid extubation to nasal ventilation appears to be more beneficial than continued mechanical ventilation. In near-term or term newborns with acute RDS, surfactant therapy has been shown to be 70% effective in improving respiratory failure.


title: Intracellular and extracellular serpins modulate lung disease

text: An imbalance between peptidases and their inhibitors leads to pulmonary disease. Imbalances occur in the adult and the neonate at risk for a specific set of lung pathologies. Serpins (serine peptidase inhibitors) make up the major source of antipeptidase activity in the lung. The purpose of this review is to describe the serpin mechanism of inhibition, their roles in the normal and pathological lung and their potential as therapeutic agents.