title: Pretreatment with interleukin 35-engineered mesenchymal stem cells protected against lipopolysaccharide-induced acute lung injury via pulmonary inflammation suppression

text: Acute lung injury (ALI)-triggered pulmonary injury has been associated with high mortality, despite advances in drug treatment and supportive therapy. Remarkable progress has been made in attenuating the inflammatory injury associated with ALI using mesenchymal stem cells (MSCs)-based cell and gene therapy. However, to date, the benefits of interleukin-35 (IL-35)-modified MSCs in ALI intervention have not been investigated. In the present study, adult male C57BL/6 mice randomly received intravenous infusion of adipose-derived mesenchymal stem cells (ADSCs) constitutively expressing IL-35 (IL-35-GFP-ADSCs) or GFP (GFP-ADSCs) via retrovirus-mediated transduction (8 × 10(5) cells per mice) or isotonic saline 7 days before ALI modeling to investigate the effect and related mechanism. ALI was performed by lipopolysaccharide (LPS) inhalation for 24 h. Normal mice served as the sham group. The results indicated that compared with GFP-ADSCs, IL-35-modified ADSCs significantly increased cellular and pulmonary IL-10 and IL-35 production. Pretreatment with IL-35-ADSCs markedly reduced body weight loss, pulmonary wet/dry weight ratio and pathological injury. The PO(2) was rescued to normal levels in mice that received IL-35-ADSCs. IL-35-ADSCs infusion apparently inhibited IL-6 release, protein leakage and MPO activity but greatly elevated IL-35 level in the bronchoalveolar lavage fluid (BALF). Splenic regulatory T cells in IL-35-ADSCs-pretreated mice got effective increase. Moreover, IL-35-ADSCs pretreatment remarkably inhibited neutrophil and macrophage infiltration and greatly decreased IL-6, tumor necrosis factor α (TNF-α) and Toll-like receptor 4 (TLR4) expression. In conclusion, pretreatment with IL-35-engineered ADSCs provided effective protection against LPS-induced ALI through suppression of pulmonary inflammation and, thus, might be a promising strategy to improve outcomes after ALI. The enhanced paracrine and immunosuppressive capacity of IL-35-ADSCs might contribute to their beneficial effects. However, further studies are needed to illuminate the detailed mechanism.


title: Inability to predict outcome of acute respiratory distress syndrome in children when using high frequency oscillation

text: OBJECTIVE: To (a) describe the experience with high-frequency oscillation (HFO) in children with acute respiratory distress syndrome (ARDS) unresponsive to conventional ventilation; (b) compare observed survival to that predicted by pediatric mortality scores and (c) determine if oxygenation index changes during HFO can predict survival. DESIGN: Retrospective, observational study. SETTING: A university hospital pediatric intensive care unit. PATIENTS: Nineteen children with ARDS (PaO(2)/FIO(2)<200) unresponsive to conventional ventilation treated with HFO from January 1995 to September 1996. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The following were recorded: demographic, arterial blood gas and ventilator variables at the time points 0, 6, 12 and 24 h after the start of HFO; PRISM in the first 24 h of admission and pediatric respiratory failure and multiple organ system failure scores on the day of starting HFO. The mortality rate was 26% (5/19). The survival was better than predicted by the Pediatric Respiratory Failure score (p<0.01). None of the scores differentiated survivors from non-survivors (p>0.25). There was no significant change in oxygenation index over the first 24 h (p>0.18). Of patients with an initial oxygenation index higher than 20 who did not have at least a 20% reduction in oxygenation index by the time 6 h, 6/9 (67%) survived (sensitivity 75%, specificity 57%). CONCLUSIONS: Survival in pediatric ARDS patients treated with HFO could not be predicted using several outcome scores or the oxygenation index (in the first 24 h). Survival was significantly better than predicted by the Pediatric Respiratory Failure score. A prospective randomized controlled trial of HFO in ARDS is warranted.


title: Surviving sepsis campaign: research priorities for sepsis and septic shock

text: OBJECTIVE: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. DESIGN: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. METHODS: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 - supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. RESULTS: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction? CONCLUSIONS: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-018-5175-z) contains supplementary material, which is available to authorized users.


title: SARS: What have we learned?

text: It's less than four months since the World Health Organization issued global warnings about a mysterious and deadly form of pneumonia. Nature's reporters pose key questions about the outbreak, and assess our preparedness to deal with future viral threats.


Mechanisms of pulmonary edema clearance: from basic research to clinical implication


docid: kmmuifit

title: Health labs focus on mystery pneumonia


Co-infection in severe influenza: a new epidemiology?


title: T cell-mediated restriction of intracerebral murine cytomegalovirus infection displays dependence upon perforin but not interferon-γ

text: The authors have previously reported that adoptive transfer of splenocytes suppresses murine cytomegalovirus (MCMV) brain infection following intracerebroventricular injection of immunodeficient mice and that depletion of Thy 1.2(+) T lymphocytes abolishes this suppressive effect. Here the authors report that splenocytes depleted of CD4(+) T lymphocytes prior to adoptive transfer retained their ability to control viral expression in the brain. In sharp contrast, depletion of the CD8(+) T-cell population prior to transfer abolished the suppressive effect, with sixfold greater expression in the brain than when undepleted splenocytes were used. The authors went on to examine the contributions of cytokine- and perforin-mediated mechanisms in controlling MCMV brain infection using splenocytes from major histocompatibility (MHC)-matched IFN-γ-knockout (GKO), and perforin-knockout (PKO) mice. When used in adoptive transfer studies, splenocytes from GKO mice controlled viral expression; however, cells from PKO mice could not control reporter gene expression or viral DNA replication in brain tissues. The authors have previously reported that the levels of the T-cell chemoattractant CXCL10 are highly elevated in the brains of MCMV-infected mice. Here the authors found that the receptor for this ligand, CXCR3, was not essential in mediating the suppressive effects of adoptive transfer. These data indicate that peripheral CD8(+) T cells control MCMV brain infection through a perforin-mediated mechanism and that neither IFN-γ nor CXCR3 play a critical role in this neuroprotective response.


title: Differential expression of neurofilament triplet proteins in brain development

text: Axonal transport studies and biochemical fractionation have led to the concept that the three ‘triplet’ proteins [approximate molecular weights 200,000 (200K), 145,000 (145K) and 68,000 (68K)] are the essential components of mammalian neurofilaments(1–5). Using a correlated biochemical and immunological approach, we have now shown that the 200K protein is under separate developmental control during rat brain differentiation and that the time of its expression differs in different regions. We were unable to detect 200K protein by immunofluorescence or in total brain filament preparations from prenatal rat brain, although the 145K and 68K proteins are both present in an apparently identical distribution. During development, progressively more 145K- and 68K-positive neurofilamentous bundles can be stained with 200K antibodies, paralleling the increasing quantities of this protein detected biochemically in brain filament preparations. We conclude that 200K protein probably has a more specialized role in neurofilament architecture and function than the other two triplet proteins.


title: Adhesion molecules in pediatric intensive care patients with organ dysfunction syndrome

text: OBJECTIVE: To determine serum concentrations of the soluble forms of vascular cell adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), and E-selectin in ventilated neonatal and pediatric intensive care patients with varying severity of multiorgan dysfunction syndrome (MODS) with or without infection-triggered organ failure. DESIGN AND SETTING: Prospective pilot study, a level III neonatal and pediatric intensive care unit at a University children's Hospital. PATIENTS: We studied 22 ventilated pediatric (n = 15) and neonatal (n = 7) intensive care patients (aged 3 days–16 years). Inclusion criteria were mechanical ventilation and signs of at least one additional organ dysfunction (cardiovascular, respiratory, neurological, hematological, or renal). MEASUREMENTS AND RESULTS: Serum concentrations of the adhesion molecules were analyzed on the day of maximum organ dysfunction score and were quantitated by a sandwich ELISA technique. The overall mortality rate was 36% (8/22). Dysfunction of three or more organ systems was defined as MODS and was associated with a significant increase in VCAM-1 serum levels relative to dysfunction of three or fewer organ systems [median 1239 ng/ml (IQR 928–1615) vs. 766 ng/ml (644–915)]. A significant difference in E-selectin serum levels was found between organ failure of infectious (median 131 ng/ml, IQR 112–146) and noninfectious origin (68 ng/ml 49–105). CONCLUSIONS: Determination of adhesion molecules in pediatric intensive care patients raises the possibility of more specific pathophysiological understanding. E-selectin showed significantly different serum levels between infectious and noninfectious causes of organ failure.


title: Effect of inhaled nitric oxide on respiratory mechanics in ventilated infants with RSV bronchiolitis

text: Objective: To evaluate the bronchodilator effect of inhaled nitric oxide (NO) in infants with respiratory failure caused by respiratory syncytial virus (RSV) bronchiolitis and to compare the effect with the one obtained by salbutamol. Design: Prospective study. Setting: Pediatric intensive care unit of a university children's hospital. Patients: Twelve acutely ill, intubated infants (mean age 4.5 months, mean weight 4.9 kg) with respiratory failure due to documented RSV bronchiolitis. Interventions: Total respiratory system resistance (Rrs) was measured by single breath occlusion at the baseline and after inhaling NO at 20, 40 and 60 ppm for 1 h, and after inhalation of a standard β (2)-agonist, salbutamol. Arterial blood gas analysis was performed at each study level on 6 of the 12 patients. Results: The baseline mean Rrs (SE) was 0.29 (0.04) cm H(2)O/ml per s. At each dose of NO, the mean Rrs (SE) was 0.28 (0.04) cm H(2)O/ml per s. With salbutamol, the mean Rrs (SE) was 0.21 (0.03) cm H(2)O/ml per s. These values were not significantly different from each other (by ANOVA). Inhaled NO produced a significant decrease in Rrs of greater than 4 times the coefficient of variation of the baseline measurement in 3 of 12 patients. Seven of 12 patients had no significant change while two patients had a significant increase in Rrs. Inhaled salbutamol produced a significant decrease in Rrs in 5 of 11 patients, while 6 showed no change in Rrs. Conclusion: Inhaled NO has no apparent bronchodilator effect in the majority of acutely ill infants with RSV bronchiolitis and does not appear to provide any additional benefit over the use of salbutamol. The clinical benefit of inhaled NO as a bronchodilator is questionable under these conditions.


docid: ofytlmdm

title: Aspergillosis in the ICU: The glass half-empty?


title: Infant lung function testing in the intensive care unit

text: As a result of the previous shortage of tools to assess objectively the overall physiological status of the respiratory system in infants and young children, it has been difficult to measure the degree of physiological disorder or the response to therapy in respiratory diseases such as BPD, the pediatric version of ARDS, bronchiolitis, pneumonia, asthma and croup in this patient population. The newborn — four-year old child is particularly difficult to study because of their lack of cooperation and size. The recent progress in computer technology made pulmonary function testing available for this age range and opened up new possibilities for monitoring changes in disease processes affecting the respiratory system. This may improve medical management of infants and children with lung and heart diseases in particular. In 1989, Shannon [49] proposed in this Journal that the minimum physiological information needed for the intelligent use of mechanical ventilation (particularly if lower airway and/or pulmonary parenchymal disease was apparent) required the measurement of at least 4 variables: i) arterial partial pressure of carbon dioxide; ii) arterial oxygen saturation; iii) the mechanical time constant of the lung and iv) FRC. In many circumstances, arterial CO(2) is approximated by alveolar (end-tidal) CO(2) and the arterial oxygen saturation is obtained from pulse oximetry accurately if perfusion is adequate. The mechanical time constant and FRC are easily measured by the techniques described above and together provide important information concerning appropriate ventilator settings for a given disease. The described techniques bring new insights and awareness, but also new responsibilities in the management of infants and children with respiratory compromise. Not all of these techniques need to be applied to all infants in the ICU. Not all the assumptions upon which some of the techniques we have described are based will prove true. Any such methods which do not withstand solid scientific testing must be quickly discarded and replaced with better and (hopefully) easier methods.


title: ARDS caused by herpes simplex virus pneumonia in a patient with Crohn's disease: a case report

text: Pneumonia caused by herpes simplex virus type 1 (HSV1) is rare and occurs in severely immunosuppressed patients. HSV1 can be detected in bronchoalveolar lavage (BAL) from patients presenting with respiratory failure, but its direct effect on disease is difficult to prove. We demonstrate the causative role of HSV1 in the case of a 44-year-old male with Crohn's disease who presented to the intensive care unit with the acute respiratory distress syndrome after surgery. BAL cells were cultured and immunofluorescence confirmed the presence of HSV1 during the first weeks of illness. Increased IgG titers confirmed the diagnosis of a recurrent HSV1 infection. A lung biposy specimen showed fibroproliferation without pathogens. Immunosuppressive therapy had been stopped and acyclovir was introduced at this time. The diagnostic difficulties in this patient underline the importance of early recognition of viral infection as a potential cause of severe pneumonia in severely ill, immunocompromised patients.


title: Improved oxygenation after discontinuing neuromuscular blockade

text: Objective: To evaluate the effects of prolonged neuromuscular blockade (NMB) on oxygenation and duration of mechanical ventilation in children with respiratory failure. Design: Retrospective case control study. Setting: The pediatric intensive care unit (PICU) of a tertiary university hospital. Patients: All children (n=68) in the PICU ventilated for pulmonary parenchymal disease for 3 days or longer over a 412 year period. Interventions: None. Measurements and results: Diagnoses, pediatric risk of mortality scoring, indications for, and duration of, mechanical ventilation and neuromuscular blockade, and blood gas data with corresponding ventilator parameters were extracted from the medical records. Twenty-eight patients received NMB at the initiation of mechanical ventilation and this was continued for 72 h or longer. Cessation of NMB was associated with a significant improvement in ventilator parameters and oxygenation index. The subset of children with respiratory syncytial virus disease (RSV) receiving prolonged NMB had longer ventilator courses compared to those in whom NMB was not used, despite similar demographics, severity of illness and oxygenation impairment. Conclusions: Stopping NMB is associated with a rapid improvement in oxygenation and prolonged use of NMB in children with RSV is associated with a protracted ventilatory course. Definition: Oxygenation index (OI)(*): Mean Airway Pressure ×FiO(2)×100/PaO(2) (*) Higher scores represent deterioration in oxygenation


PS 0420-0716


title: Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure

text: Objectives: To clarify the patterns of pulmonary tuberculosis (TB) that should result in a high index of suspicion, to increase the chances of early therapy and to identify predictors of 30-day mortality. Patients and methods: Retrospective, 7-year study in two medical intensive care units (ICUs). All patients admitted with pulmonary TB were enrolled. Clinical and laboratory data at admission and events within 48 h of admission were collected. Predictors of 30-day mortality were identified by univariate and multivariate analysis. Results: The study included 99 patients with a median age of 41 years. Immunodeficiency was present in 60 patients, including 38 with AIDS. Fifty-nine patients had pulmonary TB alone, 22 also had extrapulmonary TB and 18 had miliary. All 99 patients were admitted for acute respiratory failure, some also with shock (20), neurologic disorders (18) or acute renal failure (10). Mechanical ventilation was needed in 50 patients; 22 patients met criteria for acute respiratory distress syndrome (ARDS). The 30-day mortality rate was 26.2%. Four factors independently predicted mortality: a time from symptom onset to treatment of more than 1 month (OR, 3.49; CI, 1.20–10.20), the number of organ failures (OR, 3.15; CI, 1.76–5.76), a serum albumin level above 20 g/l (OR, 3.96; CI, 1.04–15.10), and a larger number of lobes involved on chest radiograph (OR, 1.83; CI, 1.12–2.98). Conclusion: Delayed clinical suspicion and treatment of active pulmonary TB with respiratory failure may contribute to the persistently high mortality rates in ICU patients with these diseases.


Year in review in Intensive Care Medicine 2013: III. Sepsis, infections, respiratory diseases, pediatrics


title: Bronchoscopy in the intensive care unit

text: The development of the flexible, fiberoptic bronchoscope has made bronchoscopic examinations possible in ICU patients undergoing mechanical ventilation. Over the years, the number of such procedures has greatly increased, with both diagnostic and therapeutic objectives, such as performing difficult intubation, management of atelectasis and hemoptysis, diagnosis of nosocomial pneumonia in ventilated patients, and early detection of airway lesions in selected situations, such as high-frequency ventilation. The complication rate can be kept low if the endoscopist has a precise knowledge of the many pathophysiological and technical facets particular to bronchoscopy under these difficult conditions. This article reviews some of these aspects, in the light of our personal experience.


title: Capacity of purified Lyt-2(+) T cells to mount primary proliferative and cytotoxic responses to Ia(−) tumour cells

text: Allogeneic gene products of the major histocompatibility complex, the HLA complex in man and the H–2 complex in mice, induce T lymphocytes to exert powerful mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML). In mice, the subset of T cells carrying the L3T4 surface antigen but lacking the Lyt-2 antigen responds predominantly to H–2 class II (la) differences whereas the L3T4(−) Lyt-2(+) subset reacts to class I (K/D) differences(1,2). For primary responses the stimulus for MLR and CML appears to be controlled by Ia(+) cells of the macrophage/dendritic cell lineages, for both L3T4(+) and Lyt-2(+) cells(3–6). The finding that la(+) cells are required for responses involving Lyt-2(+) cells has been taken to imply that triggering of these cells is controlled by la-restricted L3T4(+) cells(7,8). Lyt-2(+) cells have thus come to be regarded as crippled cells which are heavily dependent on ‘help’ from other T cells(9–11). This well-entrenched view is challenged by evidence presented here that purified Lyt-2(+) cells can give high primary responses to certain Ia(−) tumour cells in vitro.


title: Chinese bioscience: The sequence factory

text: The bold ambitions of one institute could make China the world leader in genome sequencing. David Cyranoski asks if its science will survive the industrial ramp-up.


title: Markers of tissue hypoperfusion in pediatric septic shock

text: Objective: To describe measurements of global oxygenation parameters, markers of splanchnic hypoperfusion and those of metabolic activity related to cellular energy production among critically ill children with septic shock.¶Design: Clinical study of a series of cases.¶Patients and participants: 11 previously healthy children with septic shock admitted to the pediatric intensive care unit (ICU) of a university hospital.¶Interventions: None.¶Measurements and results: Oxygen consumption, oxygen delivery (DO(2)), serum bicarbonate, arterial pH, gastric intramucosal pH (pHi), gastroarterial carbon dioxide tension gradient, serum lactate, pyruvate, lactate to pyruvate ratio (L/P), ketone body ratio, and the esterified to free carnitine ratio were measured serially at 0, 6, 12, 24, 36, and 48 h after admission to the pediatric ICU. All children survived. One patient failed to show supranormal DO(2) ( > 570 ml/min per m(2)). Normalization of serum bicarbonate and lactate were associated with patient recovery. One patient presented an increasingly abnormal L/P ratio with normal lactate levels, suggesting an increased utilization of pyruvate rather than an increased cytosolic redox potential. Although values of gastric pHi < 7.30 were observed in 43 % of samples, serial measurements in individuals showed significant variability and unpredictable trends. Free fatty acid concentrations, ketone body production, and carnitine levels remained within the normal range.¶Conclusions: In this study, trends in serum bicarbonate and lactate somewhat characterized the recovery of children with septic shock. Based on our data, it is unclear how other markers may have been used to modify therapy.


Supplement 2 September 2011


Septic shock caused by Mycobacterium tuberculosis in a non-HIV patient


title: Respiratory response to salbutamol (albuterol) in ventilator-dependent infants with chronic lung disease: pressurized aerosol delivery versus intravenous injection

text: OBJECTIVE: To compare the effects of intravenously injected with inhaled salbutamol in ventilator dependent infants with chronic lung disease (CLD). DESIGN: Prospective randomized study in which each patient served as his/her own control. SETTING: Multidisciplinary neonatal and pediatric ICU. PATIENTS: 8 ventilator dependent premature infants with CLD. INTERVENTIONS: Salbutamol, 10 μg/kg was given intravenously, and 10–19 h later, twice 100 μg as pressurized aerosol, or vice versa, sequence randomized. The pressurized aerosol was delivered by a metered dose inhaler into a newly developed aerosol holding chamber, integrated into the inspiratory limb of the patient circuit. Respiratory system mechanics were assessed by the single breath occlusion method before and 10 and 60 min after drug administration. MEASUREMENTS AND RESULTS: Compliance improved significantly after intravenous injection (0.48±0.18 to 0.67±0.16, p<0.01 and 0.59±0.23 ml/cmH(2)O/kg, NS, (mean±1 SD) and after inhalation (0.46±0.19 to 0.64±0.32,p<0.01 and 0.56±0.31 ml/cmH(2)O/kg, NS). Resistance decreased after i.v. use (0.38±0.17 to 0.25±0.11,p<0.001 and 0.25±0.10 cmH(2)O/ml/s, NS) and after inhalation (0.35±0.12 to 0.27±0.09,p<0.01 and 0.28±0.12 cmH(2)O/ml/s, NS). Heart rate increased significantly after both routes of application, whereas mean arterial pressure, respirator settings, FIO(2), transcutaneous SO(2) and capillary PCO(2) did not change. CONCLUSIONS: Inhaled and intravenous salbutamol improves pulmonary mechanics to the same extent with comparable side effects, and may therefore be used to facilitate weaning from respirators.


Respiratory distress syndrome and septic shock due to varicella in an HIV-infected adult


Kidney histopathological findings in fatal pandemic 2009 influenza A (H1N1)


title: Regulation of human insulin gene expression in transgenic mice

text: Insulin is a polypeptide hormone of major physiological importance in the regulation of fuel homeostasis in animals (reviewed in refs 1, 2). It is synthesized by the (β)-cells of pancreatic islets, and circulating insulin levels are regulated by several small molecules, notably glucose, amino acids, fatty acids and certain pharmacological agents. Insulin consists of two polypeptide chains (A and B, linked by disulphide bonds) that are derived from the proteolytic cleavage of proinsulin, generating equimolar amounts of the mature insulin and a connecting peptide (C-peptide). Humans, like most vertebrates, contain one proinsulin gene(3,4), although several species, including mice(5) and rats(6,7), have two highly homologous insulin genes. We have studied the regulation of serum insulin levels and of insulin gene expression by generating a series of transgenic mice containing the human insulin gene. We report here that the human insulin gene is expressed in a tissue-specific manner in the islets of these transgenic mice, and that serum human insulin levels are properly regulated by glucose, amino acids and tolbutamide, an oral hypoglycaemic agent.


title: Avian flu: Are we ready?

text: On the cover, a Shanghai commuter takes precautions during the 2003 avian influenza outbreak. It is nearly 40 years since the last worldwide influenza pandemic, and though these things don't run to an orderly timetable, many believe that it is only a matter of time — not much time at that — until the next one. This adds to the public health implications of the recent avian influenza outbreaks in Hong Kong in 1997, 1998 and 2002/3, and the continuing spread of avian influenza in poultry populations in Asia. This week, in a series of News Features and Commentary pieces, we cover the ground on one of the major health concerns of the day. Turn to page 399 for an overview, and to page 385 for editorial comment. The latest developments are covered in News, on pages 390 and 391.


title: First past the post

text: From the moment the mysterious illness known as SARS was declared a global threat to health, virologists were racing to develop a diagnostic test. Alison Abbott visits the tiny German lab that got there first.


title: Treatment of sepsis in an intensive care unit

text: The management of severe bacterial sepsis is an integral part of intensive care medicine. Early and appropriate treatment with antimicrobials positively affects mortality and significantly reduces the time spent in both intensive care and the hospital. Drug choice is usually made on a “best guess” basis and instituted prior to receipt of appropriate blood, sputum, urine or drainage culture results. Bactericidal drugs should be given in combination, delivered by intravenous bolus and directed towards broad cover of all likely pathogens. Aminoglycoside/ureidopenicillin combinations are synergistic and widely used — often combined with metronidazole. Aminoglycoside toxicity can be reduced by giving the drug once daily (OD) rather than by traditional multiple daily dosing (MDD) and by measuring peak and trough serum levels. Efficacy is increased by attention to the peak serum level/MIC ratio which determines the response to treatment. Several newer agents have been more recently introduced. These drugs include ceftazidime, imipenem/cilastatin, the quinolones and clavulanic acid/semisynthetic penicillin combinations. Other newer drugs currently under evaluation include aztreonam, teicoplanin, the penems and carbapenems.


docid: suqvyeac

title: WHO's in charge?

text: Global health remains firmly on the G8 agenda — for better or worse.


title: High frequency oscillatory ventilation for respiratory failure due to RSV bronchiolitis

text: OBJECTIVE: To describe the time course of high frequency oscillatory ventilation (HFOV) in respiratory syncytial virus (RSV) bronchiolitis. DESIGN: Retrospective charts review. SETTING: A tertiary paediatric intensive care unit. PATIENTS AND PARTICIPANTS: Infants with respiratory failure due to RSV infection. INTERVENTION: HFOV. MEASUREMENTS AND RESULTS: Pattern of lung disease, ventilatory settings, blood gases, infant’s vital parameters, sedation and analgesia during the periods of conventional mechanical ventilation (CMV, 6 infants), after initiation of HFOV (HFOVi, 9 infants), in the middle of its course (HFOVm), at the end (HFOVe) and after extubation (Post-Extub) were compared. All infants showed a predominant overexpanded lung pattern. Mean airway pressure was raised from a mean (SD) 12.5 (2.0) during CMV to 18.9 (2.7) cmH(2)O during HFOVi (P < 0.05), then decreased to 11.1(1.3) at HFOVe (P < 0.05). Mean FiO(2) was reduced from 0.68 (0.18) (CMV) to 0.59 (0.14) (HFOVi) then to 0.29 (0.06) (P < 0.05) at HFOVe and mean peak to peak pressure from 44.9 (12.4) cmH(2)O (HFOVi) to 21.1 (7.7) P < 0.05 (HFOVe) while mean (SD) PaCO(2) showed a trend to decrease from 72 (22) (CMV) to 47 (8) mmHg (HFVOe) and mean infants respiratory rate a trend to increase from 20 (11) (HFOVi) to 34 (14) (HFOVe) breaths/min. With usual doses of sedatives and opiates, no infant was paralysed and all were extubated to CPAP or supplemental oxygen after a mean of 120 h. CONCLUSION: RSV induced respiratory failure with hypercapnia can be managed with HFOV using high mean airway pressure and large pressure swings while preserving spontaneous breathing.


title: The impact of delirium in the intensive care unit on hospital length of stay

text: Study objective: To determine the relationship between delirium in the intensive care unit (ICU) and outcomes including length of stay in the hospital. Design: A prospective cohort study. Setting: The adult medical ICU of a tertiary care, university-based medical center. Participants: The study population consisted of 48 patients admitted to the ICU, 24 of whom received mechanical ventilation. Measurements: All patients were evaluated for the development and persistence of delirium on a daily basis by a geriatric or psychiatric specialist with expertise in delirium assessment using the Diagnostic Statistical Manual IV (DSM-IV) criteria of the American Psychiatric Association, the reference standard for delirium ratings. Primary outcomes measured were length of stay in the ICU and hospital. Results: The mean onset of delirium was 2.6 days (S.D.±1.7), and the mean duration was 3.4±1.9 days. Of the 48 patients, 39 (81.3%) developed delirium, and of these 29 (60.4%) developed the complication while still in the ICU. The duration of delirium was associated with length of stay in the ICU (r=0.65, P=0.0001) and in the hospital (r=0.68, P<0.0001). Using multivariate analysis, delirium was the strongest predictor of length of stay in the hospital (P=0.006) even after adjusting for severity of illness, age, gender, race, and days of benzodiazepine and narcotic drug administration. Conclusions: In this patient cohort, the majority of patients developed delirium in the ICU, and delirium was the strongest independent determinant of length of stay in the hospital. Further study and monitoring of delirium in the ICU and the risk factors for its development are warranted.


docid: paopzcma

title: Alveolar epithelium and Na,K-ATPase in acute lung injury

text: Active transport of sodium across the alveolar epithelium, undertaken in part by the Na,K-adenosine triphosphatase (Na,K-ATPase), is critical for clearance of pulmonary edema fluid and thus the outcome of patients with acute lung injury. Acute lung injury results in disruption of the alveolar epithelial barrier and leads to impaired clearance of edema fluid and altered Na,K-ATPase function. There has been significant progress in the understanding of mechanisms regulating alveolar edema clearance and signaling pathways modulating Na,K-ATPase function during lung injury. The accompanying review by Morty et al. focuses on intact organ and animal models as well as clinical studies assessing alveolar fluid reabsorption in alveolar epithelial injury. Elucidation of the mechanisms underlying regulation of active Na(+) transport, as well as the pathways by which the Na,K-ATPase regulates epithelial barrier function and edema clearance, are of significance to identify interventional targets to improve outcomes of patients with acute lung injury.


title: Severe flu management: a point of view

text: Annual flu seasons are typically characterized by changes in types and subtypes of influenza, with variations in terms of severity. Despite remarkable improvements in the prevention and management of patients with suspected or laboratory-confirmed diagnosis of influenza, annual seasonal influenza continues to be associated with a high morbidity and mortality. Admission to the intensive care unit is required for patients with severe forms of seasonal influenza infection, with primary pneumonia being present in most of the cases. This review summarizes the most recent knowledge on the diagnosis and treatment strategies in critically ill patients with influenza, focused on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, and supportive measures. The review focuses on diagnostic testing methods, antiviral therapy, use of corticosteroids, antibacterial and antifungal therapy, supportive measures and relevant existing evidence, in order to provide the non-expert clinician a useful overview. An enhanced understanding of current diagnostic and treatment aspects of influenza infection can contribute to improve outcomes and reduce mortality among ICU patients with influenza.


title: Lessons from a pandemic

text: It is time to assess what worked, and what didn't, in the global efforts to cope with swine flu.


title: Requirement for c-ras proteins during viral oncogene transformation

text: Many retroviral oncogenes have been classified into one of several categories based on structure, enzymology and cellular localization(1). These genes originated from host cells and are probably derived from genes normally involved in the control of cell proliferation(2). The cellular counterparts of three oncogenes have been identified as a growth factor or growth factor receptor(3–6); related oncogenes include receptor-like membrane proteins which often express tyrosine kinase activity. These growth factor-related oncogenes are structurally and biochemically distinct from the membrane-associated ras gene family, which bind and hydrolyse GTP(7–9). Oncogenes localized primarily in the cytoplasm which probably have serine kinase activity, have also been identified(10–12). Although the structure and biochemistry of many oncogenes have been extensively studied, relatively little is known about the functional relationships of oncogene proteins within the cell. An opportunity to study such interaction is provided by the identification of a monoclonal antibody that neutralizes cellular ras proteins when microinjected into cells(13). It has been shown previously that the injected antibody inhibits the initiation of S-phase in NIH 3T3 cells(14). In the present study we injected this monoclonal antibody into NIH 3T3 cells transformed by a variety of oncogenes. The results show that transformation by three growth factor receptor-like oncogenes depends on c-ras proteins, while transformation by two cytoplasmic oncogenes appears to be independent of c-ras protein.


title: A pandemic warning?

text: Introduction of new influenza type-A viruses, carrying different combinations of the viral envelope glycoproteins haemagglutinin (H) and neuraminidase (N), have led to three major pandemics of influenza in humans this century. Phylogenetic evidence suggests that these viruses have originated from avian influenza A viruses, either unchanged or after reassortment with humaninfluenza A viruses. In aquatic birds, all of the known H and N antigenic varieties (15 varieties carry H, nine carry N envelope glycoproteins) apparently circulate in a genetically conserved fashion. Viruses carrying the H1N1, H2N2 and H3N2 combinations were responsible for the Spanish flu of 1918, the Asian flu in 1957 and Hong Kong flu in 1968, respectively(1). An influenza A virus of the H5N1 subtype has now been identified in a human patient, raising discussions about its potential to spark a new human influenza pandemic.


docid: liegoozc

title: Metabolomic profile of acute respiratory distress syndrome of different etiologies


title: Not so secure after all

text: How safe are our microbiology labs?


Lung recruitability in ARDS H1N1 patients


title: Financing global health emergency response: outbreaks, not agencies

text: Effectively responding to global health emergencies requires substantial financial commitment from many stakeholders, including governments, multilateral agencies, and nongovernmental organizations. A major current policy challenge needs attention: how to better coordinate investment among actors aiming to address a common problem, disease outbreaks. For donors who commit colossal sums of money to outbreak response, the current model is neither efficient nor transparent. Innovative approaches to coordinate financing have recently been tested as part of a broader development agenda for humanitarian response. Adopting a system that enables donors to invest in disease outbreaks rather than actors represents an opportunity to deliver a more cost-effective, transparent, and unified global response to infectious disease outbreaks. Achieving this will be challenging, but the World Health Organization (WHO) must play a vital role. New thinking is required to improve emergency response in an increasingly crowded and financially convoluted global health arena.


Fear of human pandemic grows as bird flu sweeps through Asia


Taiwan left isolated in fight against SARS


title: p63(+)Krt5(+) distal airway stem cells are essential for lung regeneration

text: Lung diseases such as chronic obstructive pulmonary disease(1) and pulmonary fibrosis(2) involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia(3,4) or acute respiratory distress syndrome(5,6) often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process(7). Here we show that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature13903) contains supplementary material, which is available to authorized users.


title: Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study

text: PURPOSE: To determine clinical predictors associated with corticosteroid administration and its association with ICU mortality in critically ill patients with severe influenza pneumonia. METHODS: Secondary analysis of a prospective cohort study of critically ill patients with confirmed influenza pneumonia admitted to 148 ICUs in Spain between June 2009 and April 2014. Patients who received corticosteroid treatment for causes other than viral pneumonia (e.g., refractory septic shock and asthma or chronic obstructive pulmonary disease [COPD] exacerbation) were excluded. Patients with corticosteroid therapy were compared with those without corticosteroid therapy. We use a propensity score (PS) matching analysis to reduce confounding factors. The primary outcome was ICU mortality. Cox proportional hazards and competing risks analysis was performed to assess the impact of corticosteroids on ICU mortality. RESULTS: A total of 1846 patients with primary influenza pneumonia were enrolled. Corticosteroids were administered in 604 (32.7%) patients, with methylprednisolone the most frequently used corticosteroid (578/604 [95.7%]). The median daily dose was equivalent to 80 mg of methylprednisolone (IQR 60–120) for a median duration of 7 days (IQR 5–10). Asthma, COPD, hematological disease, and the need for mechanical ventilation were independently associated with corticosteroid use. Crude ICU mortality was higher in patients who received corticosteroids (27.5%) than in patients who did not receive corticosteroids (18.8%, p < 0.001). After PS matching, corticosteroid use was associated with ICU mortality in the Cox (HR = 1.32 [95% CI 1.08–1.60], p < 0.006) and competing risks analysis (SHR = 1.37 [95% CI 1.12–1.68], p = 0.001). CONCLUSION: Administration of corticosteroids in patients with severe influenza pneumonia is associated with increased ICU mortality, and these agents should not be used as co-adjuvant therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-018-5332-4) contains supplementary material, which is available to authorized users.


title: Dreams of flu data

text: The lack of an accessible store of information is undermining the fight against avian flu.


title: The fight over flu

text: A proposal to restrict the planned publication of research on a potentially deadly avian influenza virus is causing a furore. Ten experts suggest ways to proceed.


docid: lcbqxeck

title: What is the daily practice of mechanical ventilation in pediatric intensive care units? A multicenter study

text: OBJECTIVE: To describe the daily practice of mechanical ventilation (MV), and secondarily, its outcome in pediatric intensive care units (PICUs). DESIGN: Prospective cohort of infants and children who received MV for at least 12 h. SETTING: Thirty-six medical surgical PICUs. PATIENTS: All consecutive patients admitted to the PICUs during 2-month period. MEASUREMENTS AND MAIN RESULTS: Of the 1893 patients admitted, 659 (35%) received MV for a median time of 4 days (25th percentile, 75%: 2, 6). Median of age was 13 months (25th percentile, 75%: 5, 48). Common indications for MV were acute respiratory failure (ARF) in 72% of the patients, altered mental status in 14% of the patients, and ARF on chronic pulmonary disease in 10% of the patients. Median length of stay in the PICUs was 8 days (25th percentile, 75%: 5, 13). Overall mortality rate in the PICUs was 15% (confidence interval 95%: 13–18) for the entire population, 50% (95% CI: 25–74) in patients who received MV because of acute respiratory distress syndrome, 24% (95% CI: 16–35) in patients who received MV for altered mental status and 16% (95% CI: 9–29) in patients who received MV for ARF on chronic pulmonary disease. CONCLUSION: One in every 3 patients admitted to the PICUs requires ventilatory support.. The ARF was the most common reason for MV, and survival of unselected infants and children receiving MV for more than 12 h was 85%. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2225-5


title: Alveolar fluid clearance in acute lung injury: what have we learned from animal models and clinical studies?

text: BACKGROUND: Acute lung injury and the acute respiratory distress syndrome continue to be significant causes of morbidity and mortality in the intensive care setting. The failure of patients to resolve the alveolar edema associated with these conditions is a major contributing factor to mortality; hence there is continued interest to understand the mechanisms of alveolar edema fluid clearance. DISCUSSION: The accompanying review by Vadász et al. details our current understanding of the signaling mechanisms and cellular processes that facilitate clearance of edema fluid from the alveolar compartment, and how these signaling processes may be exploited in the development of novel therapeutic strategies. To complement that report this review focuses on how intact organ and animal models and clinical studies have facilitated our understanding of alveolar edema fluid clearance in acute lung injury and acute respiratory distress syndrome. Furthermore, it considers how what we have learned from these animal and organ models and clinical studies has suggested novel therapeutic avenues to pursue.


Structure of Ribonucleic Acid


8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts


title: Structural basis of West Nile virus neutralization by a therapeutic antibody

text: West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses(1). In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop(2,3,4). Humoral immunity has an essential protective function early in the course of West Nile virus infection(5,6). Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments(7), and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature03956) contains supplementary material, which is available to authorized users.


10(th) European Congress of Trauma and Emergency Surgery: May 13–17, 2009 Antalya, Turkey


title: Bronchopulmonale Dysplasie (BPD)

text: OLD VS. NEW BPD: Bronchopulmonary dysplasia (BPD) was described about 50 years ago as a fibroproliferative chronic lung disease in consequence of mechanical ventilation/oxygen exposure in premature infants with respiratory distress syndrome (old BPD). Surfactant therapy with increased survival of extremely premature infants identified a new type of an immaturity-related multisystem disorder that is characterized by a stop/simplification of alveolarisation and lung capillary development (new BPD). THERAPY: To date, mainly symptomatic treatment exists. However, growth factors and stem cell therapy have recently been tested with some success in animal experiments. OUTCOME: Survivors of new BPD may have problems in adult life concerning lung and cardiovascular function, growth and neurosensory and/or motor development.


title: Surfactantsubstitutionstherapie: Ein entscheidender Durchbruch in der Behandlung des Atemnotsyndroms Frühgeborener

text: Surfactant replacement therapy is a major breakthrough in neonatal medicine. Prophylaxis or treatment of neonatal respiratory distress syndrome (RDS) with various surfactant preparations is now a clinical reality. With either strategy the incidence of air leaks and mortality is reduced; more babies with RDS survive without signs of chronic lung disease. The earlier the treatment, the better the outcome. An initial dose of 100 mg/kg can be recommended for all natural preparations, and some babies may benefit from multiple dose treatment. Meta-analyses show a consistent advantage of natural surfactant preparations over the currently available synthetic ones. There is growing evidence that surfactant may also be beneficial in pulmonary diseases of the newborn which are characterized by inactivation of the surfactant system such as meconium aspiration syndrome or neonatal pneumonia.


title: Gram-negative bacterial pneumonia with secondary aspergillosis in an AIDS patient

text: A 40-year-old, HIV-infected female patient received antibiotic treatment for a urinary tract infection. After the initial success of therapy and a symptom-free period, she developed pneumonia with septic shock and adult respiratory distress syndrome (ARDS). In spite of intensive care and respirator therapy with positive end-expiratory pressure (PEEP), she died of infectious toxic shock. Autopsy findings showed relapsing, gramnegative, bacterial pneumonia (morphologically compatible with Klebsiella pneumonia) and secondary, invasive aspergillosis. The pathogenesis and epidemiology of these unusual complications of AIDS are discussed.


title: Untersuchungen über die bronchokonstriktorische Wirkung des β-Rezeptorblockers Propranolol bei Meerschweinchen und Patienten mit Asthma bronchiale

text: 1. The bronchoconstrictor effect of propranolol aerosol was investigated on guinea-pigs and on 5 patients with bronchial asthma. 2. In guinea-pigs a 12% propranolol aerosol regulare caused severe dyspnoea similar to that observed in the anaphylactic microshock. 3. The bronchial obstruction present in asthmatics became more pronounced after inhaling a 1% or 5% propranolol aerosol. 4. In guinea-pigs and in asthmatics the propranolol effect was significantly antagonized by atropine and by hexamethonium; guanethidine and mepyramine had no effect.


SARS epidemic unmasks age-old quarantine conundrum


Silentes CTG in der 32. Schwangerschaftswoche unter Midazolam oder peripartale Infektion?


title: Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

text: Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in inflammatory and immune responses. MIF was originally discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including production of proinflammatory cytokines, glucocorticoid-induced immunomodulator, and natural killer cell inhibitory factor (NKIF), regulation of toll-like receptor expression, adherence and phagocytosis of macrophages, as well as induction of metalloproteinase. Therefore MIF is considered as a potential target protein in many pathophysiological states. In this review, considering the protein structure and the acting mechanisms of MIF, we mainly discuss the important role of MIF in pathogenesis of inflammatory diseases and graft rejection.


Abstracts der 108. Jahrestagung der Deutschen Gesellschaft für Kinder- und Jugendmedizin e.V. (DGKJ)


title: Dynamics of neutrophilic NF-kB translocation in relation to IL-8 mRNA expression after major trauma

text: OBJECTIVE: Systemic inflammation subsequent to polytrauma is connected to neutrophil (PMN) dysregulation characterized by reduced NF-kB-translocation and cytokine expression. The dynamics of NF-kB-activation as well as its down-stream regulation of IL-8-expression in PMN following major trauma remain unclear. The aim of this pilot study was to analyse NF-kB nuclear translocation in relation to IL- 8-mRNA-expression in PMN after major trauma. PATIENTS AND METHODS: PMN were isolated from blood samples of 15 major trauma patients (New Injury Severity Score, NISS > 16) drawn within 90 min and subsequently 6, 12, 24, 48, 72 h after trauma. NF-kB-translocation was analysed by Electrophoretic Mobility Shift Assay, EMSA and quantified by densitometry [arbitrary units], IL-8-mRNA-expression by RT-PCR, [copies/50 ng RNA]. Additionally, NF-kB-translocation and IL-8-expression in PMN of healthy volunteers were analysed natively (-control) and after LPS stimulation (+control). RESULTS: NF-kB-translocation and IL-8-mRNA-expression was significantly increased in polytrauma patients (n=15; NISS: 34 ± 8 [mean ± SEM]) initially. In non-survivors, NFkB- translocation was significantly increased on admission and subsequently reduced within 6 h, while it increased in the survivors group. After 24 h, a second significant increase in NF-kB-activity and IL-8-expression was found in survivors that was subsequently reduced in both groups. CONCLUSION: This pilot study has shown that a concomitant initial increase in transcriptional NF-kB-activity and IL-8 mRNA expression was observed in the early posttraumatic period which preceded the down-regulation of the innate immune system.


Abstracts der 50. Jahrestagung der Österreichischen Gesellschaft für Kinder- und Jugendheilkunde (ÖGKJ)


docid: wjkbrfkn

title: Antiphospholipidantikörpersyndrom

text: □ BACKGROUND: Antiphospholipid antibodies comprise a family of auto-antibodies mainly characterized by the presence of the lupus anticoagulant (LA) and anticardiolipin antibodies (ACA). □ CLINICAL APPEARANCE: The antiphospholipid antibody syndrome is defined by the appearance of frequent thromboses, repeated fetal losses and thrombocytopenia. Other clinical manifestations associated with APA include migraine, chorea, hemolytic anemia, heart valve disease, Budd-Chiari syndrome, perpetual pancreatitic episodes, intestinal infarctions, malignant hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or catastrophic antiphospholipid syndrome. LA and ACA occur in a variety of clinical conditions (secondary antiphospholipid antibody syndrome, SAPS), including other autoimmune disorders, infectious diseases, neoplastic disorders, in association with the use of certain drugs or in otherwise healthy individuals (primary antiphospholipid antibody syndrome, PAPS). □ TREATMENT: Patients with thrombosis associated with APA should receive long-term anticoagulation therapy, whereas treatment of asymptomatic patients seems to be not indicated, because only approximately 10% of patients with APA may develop thrombotic complications. In patients with PAPS there is no evidence that the prophylactic administration of immunosuppressive drugs will prevent thromboembolic events.


title: 30-jähriger Bodybuilder mit septischem Schock und ARDS bei Abusus anabol-androgener Steroide

text: We report the case of a 30-year-old body builder who developed a gluteal abscess at the site of injection of regularly self-administered anabolic steroids. After breaking the abscess under general anaesthesia, the patient developed septic shock and fulminant adult respiratory distress syndrome (ARDS). In addition to discussing the pathogenesis, differential diagnosis, and treatment, we focus on the immunomodulatory mechanisms of anabolic substances that may have contributed to the course of the disease in this particular patient.


Akutes Leberversagen


title: Assisted respiration using CPAP via face-mask in patients with blunt chest trauma. An alternative to intubation and mechanical ventilation: Eine Alternative zur Intubation

text: Intubation and Positive End Expiratory Pressure Ventilation (PEEP) is a well established therapeutic strategy for impaired lung function, particularly following blunt chest trauma. Complications of this regime are however also well known and pose the question why non-invasive forms of respiratory assistance such as Continuous Positive Airway Pressure (CPAP) have only gained minor popularity. In a prospective study, 30 patients who had suffered blunt chest trauma were treated with CPAP administered by mask. The regime consisted of continuous administration of CPAP by a face-mask, with gradually increasing periods of spontaneous breathing. Initially a FiO(2) of 0.33 (range 0,28–0,38) proved necessary. The initial CPAP level was 7 mbar (range 5–8) with an (Assisted Spontaneous Breathing) ASB of 15 mbar (range 13–18). FiO(2) and CPAP/ASB levels were subsequently gradually reduced until no longer necessary. In all patients intubation and ventilation was avoided by this regimen. The treatment was well accepted by all patients and common ventilation associated complications such as pneumonia did not occur. In comparison with the former standard method of treatment the average ICU stay was dramatically reduced, principally due to not having to gradually wean patients from ventilation and sedation. Other positive benefits include normal communication and feeding with active early mobilisation leading to faster recovery, both physical and psychological. We conclude that non-invasive respiratory techniques should be used more frequently and recommend further studies are undertaken to define the indications.


title: Detection of β-Herpesviruses in Polish Adult Cord Blood Stem Cell Recipients by Real-Time PCR: Single Centre Study

text: Umbilical cord blood transplantation (UCBT) is known to be associated with increased risk of infections, compared to bone marrow or peripheral blood stem cell transplantation. In viral diseases for which specific treatment is available, real-time PCR assays are reliable diagnostic tools for timely initiation of appropriate therapy and for rapid assessment of the efficacy of antiviral treatment strategies. A retrospective review of samples from a group of seven adult cord blood stem cell recipients was made. Serum samples taken up to 180 days after transplantation were examined with quantitative real-time PCR for measurement of viral load (CMV, HHV-6, and HHV-7). Cytomegalovirus (CMV) DNA was detected in samples taken from four patients (57%) in the period of 20–80 days after transplantation. Products of amplification of human herpesvirus 6 (HHV-6) DNA were found in samples taken between days 25 and 37 following UCBT from only one patient (14%). On the other hand, the majority of patients (n = 6, 86%) had HHV-7 DNA detected in the period 15–58 days after transplantation. Co-infection with HHV-7 was demonstrated at onset of all episodes of microbiologically confirmed CMV or HHV-6 infection. Our observations indicate that real-time PCR is not only useful for monitoring herpesviral infections in transplant recipients, but is also a powerful method for clarifying the relationships between the viral load and clinical symptoms. Further investigation with a much larger group of patients will be needed to confirm these observations and translate them into a clinical approach.


title: Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice

text: OBJECTIVE: Gossypol has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. METHODS: Male BALB/c mice were pretreated with gossypol 1 h before intranasal instillation of LPS. Then, 7 h after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were detected by western blot. RESULTS: Gossypol markedly attenuated the LPS-induced histological alterations in the lung and inhibited the production of TNF-α, IL-1β and IL-6. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. CONCLUSION: The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. Gossypol may be a promising potential therapeutic reagent for ALI treatment.


title: Emotionale Befindlichkeit, kognitive Leistungsfähigkeit und Lebensqualität bei HIV-Patienten: Ergebnisse einer explorativen Untersuchung

text: BACKGROUND: Due to the change of HIV disease from an acute life-threatening disease to a chronic infection, it is more psychosocial rather than therapeutic aspects that have become of interest in scientific investigations. The purpose of this exploratory study was to evaluate emotional distress, health-related quality of life (HRQoL) and cognitive performance. The diagnosis of HIV was considered a life event that may lead to post-traumatic stress syndrome. METHOD: We recruited 37 HIV-positive outpatients and assessed the frequency of depressive (BDI) and post-traumatic stress symptoms (PTSS) due to the diagnosis of HIV (IES), HRQoL (SF-36) and cognitive performance (SKT). Further, the new diagnostic concept of adjustment disorder as a stress response syndrome according to Maercker was considered. RESULTS: Of the 37 Patients, 67.6% (n=25) of the sample had a post-traumatic stress syndrome. The HIV-related PTSS was considered adjustment disorder using the concept proposed by Maercker. Fourteen patients (37.8%) suffered from a depressive syndrome, and 27% (n=10) showed cognitive deficits (minimal: n=8; mild: n=1; moderate: n =1). HIV-positive patients with PTSS had significantly unfavourable values in the SF-36 domains general health (p=0.003), vitality (p=0.007), social functioning (p=0.000), role-emotional (p=0.016) and mental health (p=0.000). CONCLUSION: HIV-infected patients may face a major risk of HIV-related PTSS in the sense of adjustment disorder according to Maercker, depression and cognitive dysfunction. The presence of emotional distress is associated with impairments in quality of life. We therefore suggest an early and comprehensive bio-psycho-social assessment and therapy of HIV-infected patients.


DEGRO 2009 15. Jahreskongress der Deutschen Gesellschaft für Radioonkologie, Radioonkologie · Medizinische Physik · Strahlenbiologie: Bremen, 11. bis 14. Juni 2009


docid: nqweauko

title: Bedeutung der angeborenen Immunantwort in der Sepsis

text: The innate immune system succeeds against the majority of infections before the adaptive immune system is activated. New findings contribute to a better understanding of the pathophysiology of sepsis and lead to the development of new therapeutic strategies. The innate immune system, being responsible for the first response to infections, can trigger adaptive immune responses in case the initial response is ineffective. Both arms of the immune system interact with each other, mainly via cell-cell-interactions but also by soluble factors, such as cytokines and chemokines. Two sub-populations of helper T-cells direct both balanced activation and inhibition of the two arms of the immune systems using specific patterns of cytokine release. Results obtained in new animal models of sepsis, taking a progressive growth of bacteria into account, have implied that existing knowledge has to be reanalyzed. The idea of sepsis as a mere “over-reaction to inflammation” has to be abandoned. Various so-called pattern recognition receptors (e.g. toll-like receptors, TLRs, NOD proteins) are located intracellularly or in the plasma membrane of innate immune cells and recognize certain patterns expressed exclusively by extracellular pathogens. Upon receptor engagement, intracellular signaling pathways lead to cellular activation, followed by release of various cytokines and anti-microbial substances. During the course of sepsis a cytokine shift towards increasing immune suppression occurs. The innate immune system also contributes to the migration of leukocytes in inflammed tissue, involving chemokines and adhesion molecules. Leukocytes also secrete the tissue factor leading to formation of thrombin. The environment in sepsis can cause disseminated intravascular coagulation (DIC), but at the same time thrombin triggers the release of chemokines and adhesion molecules through endothelial cells, which represents a positive feedback mechanism for innate immune responses. New therapeutic strategies for sepsis try to establish a well-balanced immune response. Intervention is accomplished through inhibition of inflammatory cytokines, their receptors or through activation of immunostimulatory responses.


title: Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy

text: Excessive body iron or iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which are reaching epidemic levels worldwide. Primary hemochromatosis is the most common genetic disorder with an allele frequency greater than 10% in individuals of European ancestry, while hemosiderosis is less common but associated with a much higher morbidity and mortality. Iron overload leads to iron deposition in many tissues especially the liver, brain, heart and endocrine tissues. Elevated cardiac iron leads to diastolic dysfunction, arrhythmias and dilated cardiomyopathy, and is the primary determinant of survival in patients with secondary iron overload as well as a leading cause of morbidity and mortality in primary hemochromatosis patients. In addition, iron-induced cardiac injury plays a role in acute iron toxicosis (iron poisoning), myocardial ischemia–reperfusion injury, Friedreich ataxia and neurodegenerative diseases. Patients with iron overload also routinely suffer from a range of endocrinopathies, including diabetes mellitus and anterior pituitary dysfunction. Despite clear connections between elevated iron and clinical disease, iron transport remains poorly understood. While low-capacity divalent metal and transferrin-bound transporters are critical under normal physiological conditions, L-type Ca(2+) channels (LTCC) are high-capacity pathways of ferrous iron (Fe(2+)) uptake into cardiomyocytes especially under iron overload conditions. Fe(2+) uptake through L-type Ca(2+) channels may also be crucial in other excitable cells such as pancreatic beta cells, anterior pituitary cells and neurons. Consequently, LTCC blockers represent a potential new therapy to reduce the toxic effects of excess iron.


New organization pledges scientific expertise for viral outbreaks


title: Das retikuläre Muster in der Dünnschicht-CT: Von der Morphologie zur Differenzialdiagnose

text: Major constituents of a reticular pattern in thin-section CT are thickened interlobular and intralobular septa as well as honeycombing. When thickening of the interlobular septa or honeycombing are visible as predominant features, these patterns have a limited differential diagnosis. In this context, a detailed analysis of morphologic characteristics (e.g., smooth or nodular interlobular septal thickening) and of the pattern localisation (e.g., peripheral, basal and subpleural honeycombing) is required. Thickened intralobular septa, parenchymal bands, subpleural lines and the “interface sign” are all rather non-specific findings. However, if interpreted in the context of other CT findings, a differential diagnosis may also frequently be reported.


title: Aktuelle Liquordiagnostik bei erregerbedingten Krankheiten

text: Cerebrospinal fluid (CSF) analysis is of utmost importance to establish an early diagnosis of central nervous system (CNS) infections and to start appropriate therapy. The CSF white cell count, lactate concentration and total protein levels are usually available very quickly even from non-specialized laboratories and the combination of these parameters often provides sufficient information for decision-making in emergency cases. It is, however, not always possible to identify the underlying infective agent despite further CSF analyses, such as bacterial and fungal staining, evaluation of the blood-CSF barrier function, intrathecal immunoglobulin synthesis and oligoclonal IgG bands. Therefore, close communication between the laboratory and the clinician is an important prerequisite to specify additional pathogen-related diagnostic measures for successful confirmation of the diagnosis.


Minutes of the 44th Genral Assembly of the European Association for the Study of Diabetes


title: Respiratorische Notfälle im Kindes- und Jugendalter

text: Dyspnoea, inspiratory stridor, wheeze, cyanosis and chest pain are common symptoms of respiratory emergencies in children and adolescents. The airways of infants and toddlers are narrow and soft and oxygen reserve is small. Muscle fatigue can quickly lead to respiratory insufficiency. Symptoms, diagnosis, differential diagnosis and therapy of foreign body inhalation, croup, epiglottitis, bacterial tracheitis, bronchiolitis and acute asthma are dealt with in detail.


title: Inflammatory pattern recognition receptors and their ligands: factors contributing to the pathogenesis of preeclampsia

text: PROBLEM: Preeclampsia, a pregnancy-specific hypertensive syndrome, is one of the leading causes of premature births as well as fetal and maternal death. Preeclampsia lacks effective therapies because of the poor understanding of disease pathogenesis. The aim of this paper is to review molecular signaling pathways that could be responsible for the pathogenesis of preeclampsia. METHOD OF STUDY: This article reviews the English-language literature for pathogenesis and pathophysiological mechanisms of preeclampsia based on genome-wide gene expression profiling and proteomic studies. RESULTS: We show that the expression of the genes and proteins involved in response to stress, host-pathogen interactions, immune system, inflammation, lipid metabolism, carbohydrate metabolism, growth and tissue remodeling was increased in preeclampsia. Several significant common pathways observed in preeclampsia overlap the datasets identified in TLR (Toll-like receptor)- and RAGE (receptor for advanced glycation end products)-dependent signaling pathways. Placental oxidative stress and subsequent chronic inflammation are considered to be major contributors to the development of preeclampsia. CONCLUSION: This review summarizes recent advances in TLR- and RAGE-mediated signaling and the target molecules, and provides new insights into the pathogenesis of preeclampsia.


title: Not so fast: adaptive suppression of innate immunity

text: The innate and adaptive immune systems act in concert to effectively combat infection while minimizing collater al damage caused by the host immune response. T cells of the adaptive immune system have now been shown to suppress overzealous early innate responses to infection that can lead to 'cytokine storm'–mediated death (pages 1248–1252).


title: Krebspatienten in der operativen Intensivmedizin

text: Cancer is one of the leading causes of death worldwide. New targeted and individualized therapies and drugs provide a survival benefit for an increasing number of patients, but can also cause severe side effects. An increasing number of oncology patients are admitted to intensive care units (ICU) because of cancer-related complications or treatment-associated side effects. Postoperative care, respiratory distress and sepsis are the leading causes for admission. Tumor mass syndromes and tumor lysis may require urgent treatment. Traditional anticancer chemotherapy is associated with infections and immunosuppression. Newer agents are generally well-tolerated and side effects are mild or moderate, but overwhelming inflammation and autoimmunity can also occur. Cellular treatment, such as with chimeric antigen receptor modified T‑cells, monoclonal and bispecific antibodies targeting immune effectors and tumor cells are associated with cytokine release syndrome (CRS) with hypotension, skin reactions and fever. It is related to excessively high levels of inflammatory cytokines. Immune checkpoint inhibitors can lead to immune-related adverse events (IRAEs), such as colitis and endocrine disorders. Noninfectious respiratory complications, such as pneumonitis can also occur. Recent studies revealed that short-term and medium-term survival of cancer patients is better than previously expected. In this review article we summarize diagnostic and treatment strategies for common life-threatening complications and emergencies requiring ICU admission. Furthermore, strategies for rational admission policies are presented.


title: Genomic prospecting

text: The importahce of preserving biodiversity extends beyond the discovery of new drugs to understanding how other species have dealt with medical problems we currently face.


title: Cytochemical localization of 5-hydroxydopamine in adrenergic elements of cat adrenal medulla

text: Nachweis von mit 5-Hydroxydopamin markierten Noradrenalin-Bläschen in postganglionären Nerven, wodurch die Bläschen eine elektronendichte, mit dem Elektronenmikroskop sichtbare Substanz enthalten. Solche Nerven mit positiver Reaktion für 5-OHDA werden im Nebennierenmark erwachsener Kater und nur im Gebiet noradrenalinhaltiger Zellen nachgewiesen.


title: Erweiterte Spenderkriterien der Bundesärztekammer: Untersuchung zu ihrer Anwendbarkeit als prognostisches Modell für den frühen Verlauf nach Lebertransplantation

text: INTRODUCTION: Expansion of the donor pool by the use of grafts with extended donor criteria reduces waiting list mortality with an increased risk for graft and patient survival after liver transplantation. The ability of the number of fulfilled extended donor criteria as currently defined by the German Medical Association (BÄK-Score) to predict early outcome is unclear. PATIENTS: A total of 291 consecutive adult liver transplantations (01.01.2007–31.12.2010) in 257 adult recipients were analyzed. METHODS: Primary study endpoints were 30 day mortality, 3 month mortality, 3 month patient and graft survival and the necessity of acute retransplantation within 30 days. For primary study endpoints a ROC curve analysis was performed to calculate sensitivity, specificity and overall model correctness of the BÄK score as a predictive model. Further methods included Kaplan-Meier estimates, log-rank tests, Cox regression analysis, logistic regression analysis and χ(2)-tests. RESULTS: The number of extended donor criteria fulfilled had no statistically significant influence on the primary study endpoints (p > 0.05) or on patient survival (p > 0.05). ROC curve analysis revealed areas under the curve ≤ 0.561 for the prediction of primary study endpoints (overall model correctness < 58%, sensitivity < 52%). CONCLUSIONS: The number of fulfilled extended donor criteria as currently defined by the German Medical Association is unable to predict early outcome after liver transplantation.


title: Therapie des toxischen Schocksyndroms mit hoch dosierter Immunglobulingabe

text: Background. The clinical appearance of the toxic shock syndrome (TSS) shows several parallels to the Kawasaki syndrome. The treatment of choice in Kawasaki's disease is high dose application of immunglobulins whereas a standardised treatment of TSS has not yet been defined. Case report. We report of a 14 year old girl with severe TSS which did not occur during menstruation. Treatment with high dose immunglobulins (2 g/kg KG) and antibiotics resulted in prompt recovery.


53(rd)EASD Annual Meeting of the European Association for the Study of Diabetes: Lisbon, Portugal, 11 – 15 September 2017


title: Perioperative Anämie

text: Anemia is a frequent finding, particularly in the elderly population, and usually indicative of a serious disease. The main causes of preoperative anemia are acute or chronic hemorrhage, iron deficiency, renal insufficiency, inflammatory and neoplastic diseases. A preexisting mild anemia may be enhanced or unmasked by surgically induced bleeding or repeated diagnostic phlebotomies, and by a postoperative erythropoietic dysfunction caused by the surgical trauma, irrespective of any hemorrhage. Low hemoglobin values are associated with a distinct increase of mortality and morbidity, both in the normal population and perioperatively and in the critically ill patients. The anemia-associated risk is exacerbated by preexisting cardiovascular disease, important intraoperative blood loss and advanced age. In contradiction to established therapeutical concepts, the administration of allogeneic blood beyond hemoglobin levels of 8–10 g/dl has not been found to decrease perioperative or intensive care morbidity or mortality. Rather, in addition to the inherent long-term risks of transfusions, a liberal transfusion strategy seems to increase the incidence of postoperative complications. Thus, current transfusion guidelines tend to be interpreted in an increasingly restrictive manner. Depending on the urgency of the clinical situation, the primary goal should be to diagnose and treat the underlying disease, rather than to focus on the symptom anemia. Time permitting, the patient's cardiovascular and pulmonary status should be optimized preoperatively. Furthermore, iron should be substituted to treat and prevent deficiency. Recombinant human erythropoietin has successfully been used to treat anemia of chronic renal failure and chronic disease, as well as in the perioperative and intensive care setting, and to support the efficiency of autologous programs.


title: Incidence and clinical characteristics of posttransplant lymphoproliferative disorders: report from a single center

text: In the period 1973–1998, among 2 139 allograft recipients treated with standard immunosuppression, posttransplant lymphoproliferative disorders (PTLD) developed in 19 patients (0.9 %): one plasmacytic hyperplasia, two polymorphic PTLD, one myeloma, and 15 lymphomas. PTLD developed 1 year after transplantation (tx) in 14 patients. Five patients were diagnosed at autopsy, 2 were lost to follow up, 3 died before therapy could be instituted, and 1 patient has just started chemotherapy. Of the 8 evaluable patients, 2 received acyclovir and are alive in complete remission (CR) and 6 received chemotherapy ± surgery. Of these 6, 4 died of lymphoma and/or infection, 1 died of unrelated causes in CR, and 1 is alive in CR. PTLD is a severe complication of tx, usually running an aggressive course which may preclude prompt diagnosis and treatment. Nevertheless, therapy is feasible and must be tailored on the histologic subtype. Seventy-four percent of patients were diagnosed with late-onset PTLD stressing the need for long-term follow up.


title: Drugs that made headlines in 2014

text: This year's newsworthy drugs made major strides against infectious diseases, cancer and more. Some others received attention for controversies they stemmed or stomped. Here is a look at the therapies that leapt forward, some that are in limbo, and others that fell by the wayside.


title: Stellenwert der Gentherapie in Unfallchirurgie und Orthopädie

text: Modern molecular and genetic technologies enable the modification of a cellular genome through transfer of specific genes. The various procedures alter specific cell functions, which allow the transfected cell to produce any encoded transgene information. The transfected cell then synthesizes proteins that are normally not produced or only in very small amounts. Numerous animal studies have demonstrated that gene therapy may support and accelerate the healing and regeneration of specific tissues such as skin, tendons, cartilage, and bones. Currently, further animal studies are evaluating new vectors with reduced immunogenicity in the continuous effort to improve the efficacy and safety of gene transfer. In the forthcoming decade we expect gene therapy to have an important influence on the treatment of fractures, cartilage lesions, and infection.


title: Bronchoalveolar lavage proteins

text: Since the discovery of the extra-cellular lining material of the lung and the possibility harvesting this source by endobronchial lavage this material has been the object of many studies directed to analyze its components, function and possible change in the diseased lung. The best known component of the extra-cellular lining material is the phospholipid and its fatty acid composition. But also on the cellular material much emphasis has been taken with the aim using its cytology as diagnostic parameter. However, very few informations were obtained about the protein material also washed out during the endobronchial lavage. As it was demonstrated by immunological methods the proteins of the extra-cellular lining material consist of serum identical proteins and those being obviously specific for the lung tissue. As found, most serum identical proteins occure in the same amounts as found in the blood serum, and the molecular weight in general range up to 160,000 daltons indicating that there must be a restriction in passage of high molecular weight proteins through the lumen walls of the endothelium. Some proteins, IgG, IgA, do occure in a higher level in the extra-cellular lining material leading to the suggestion that these proteins were synthesized and secreted by the lung tissue itself. — The molecular weight of the lung specific proteins range from 16,000–340,000 daltons. Under reducing conditions however, for all species listed, two classes of subunits −36,000 and 12,000 daltons — result, indicating that these proteins might have comparable functions in the different species. The exact function of these specific proteins as well as the serum identical proteins till now is not known. One can only speculate that the serum identical proteins will have the same function in plasma and the lung, and that the specific proteins are involved in the formation in the surfactant system. Different amounts of lung specific proteins in lavage of disease lungs suggest that their estimation might be an additional useful parameter in diagnosis of lung diseases.


Abstracts der 107. Jahrestagung der Deutschen Gesellschaft für Kinder- und Jugendmedizin e.V. (DGKJ)


SARS spreads new outlook on quarantine models


24. Jahrestagung der Gesellschaft für Pädiatrische Pneumologie: Erlangen, 18.–20. April 2002 Tagungspräsident: Prof. Dr. Th. Zimmermann


title: Die „künstliche Niere“: Indikation und praktische Anwendung

text: Mit der künstlichen Niere wurde die moderne Medizin mit einem Apparat bereichert, „which might tide over a dangerous crisis“ (Abel). Sie kann jedoch keinesfalls als vollwertiger Ersatz für ein menschliches Organ angesehen werden. Obwohl die Möglichkeiten der künstlichen Niere sowie auch ihre Grenzen allgemein bekannt sind, blieben viele Gebiete ihrer Anwendung unerforscht. Hier bietet sie ein lohnendes Betätigungsfeld für den klinischen Wissenschaftler. Erfahrungen in der gesamten Welt, besonders in Amerika, Schweden und Frankreich haben den hohen Wert der „künstlichen Niere“ in der modernen Therapie bestätigt. Ihre Anwendung ist für viele Menschen lebensrettend. Ihre Entwicklung läßt das Problem besonders der akuten Niereninsuffizienz in einem neuen, hoffnungsvolleren Licht erscheinen.


title: Perioperative Anämietoleranz: Mechanismen, Einflussfaktoren, Grenzen

text: The expected cost explosion in transfusion medicine (increasing imbalance between donors and potential recipients, treatment of transfusion-associated complications) increases the socio-economic significance of specific institutional transfusion programs. In this context the estimated use of the patient’s physiologic tolerance to anemia enables 1) the tolerance of larger blood losses (loss of “diluted blood”), 2) the onset of transfusion to the time after surgical control of bleeding to be delayed and 3) the perioperative collection of autologous red blood cells. The present review article summarizes the mechanisms, influencing factors and limits of this natural tolerance to anemia and deduces the indication for perioperative red blood cell transfusion. Under strictly controlled conditions (anesthesia, normovolemia, complete muscular relaxation, hyperoxemia, mild hypothermia) extremely low hemoglobin concentrations [Hb <3 g/dl (<1.86 mmol/l)] are tolerated without transfusion by individuals with no cardiopulmonary disease. In the clinical routine these situations are limited to borderline situations e.g. unexpected massive blood losses in Jehovah’s Witnesses or unexpected shortcomings in blood supply. The current recommendations coincide to the effect that perioperative red blood cell transfusion 1) is unnecessary up to a Hb concentration of 10 g/dl (6.21 mmol/l) even in older patients with cardiopulmonary comorbidity and 2) is only recommended in cases of Hb <6 g/dl (<3.72 mmol/l) in otherwise healthy subjects including pregnant women and children. Critically ill patients with multiple trauma and sepsis do not seem to benefit from transfusions up to Hb concentrations >9 g/dl (>5.59 mmol/l). In cases of massive hemorrhaging and diffuse bleeding disorders the maintenance of a Hb concentration of 10 g/dl (6.21 mmol/l) seems to contribute to stabilization of coagulation.


title: Anästhesie und perioperative Immunfunktion

text: Innate and acquired immunity plays a pivotal role in the host defense response. Pain, stress, necrotic tissue and invading microorganisms are known modulators of the complex immune response of patients undergoing major surgery. Anaesthesia itself or perioperative interventions of the anaesthesiologist may substantially alter the immune function with potential impact on the postoperative course. For instance, transfusion of allogenic blood and administration of dopamine or metoclopramide may interfer with immunity. Stress and pain are associated with immune tolerance, increased susceptibility to infection and tumor spreading in animal models. Thus, anaesthesia may – through modulation of the neurohumoral stress response – indirectly affect immunity of the surgical patient. In particular epidural anaesthesia and/or administration of epidural or spinal opioids seem to attenuate the stress response with beneficial effects on cellular and humoral immunity. In addition, anaesthetics, such as etomidate, propofol, or thiopentone and opioid analgesics may directly affect function of immune competent cells. However, these actions may only be apparent with high or supraclinical concentrations and/or long-term exposure. Regarding the latter, evidence suggests that long-term sedation using thiopentone in neurosurgical patients is paralleled by infectious complications in a dose-dependent manner. At present, no data are available regarding the significance of the observed alterations associated with various anaesthetic procedures of the incidence of postoperative complications associated with impaired immunity, such as infection or metastatic spreading in oncological surgery.


title: Safety in anesthesia

text: The specialty of anesthesiology has made extraordinary advances in anesthesia safety. Yet, anesthetic mortality and morbidity continue to be far from tolerable. Efforts to enhance safety in anesthesia must include adherence to explicit and implicit safety standards, must make use of equipment that offers modern safety features, must seek to detect and correct developing safety threats as early as possible and must have a structured system to analyze problems and to institute remedies to prevent their recurrence.


title: Thrombozytentransfusion: Klinik, Kontrollen und Komplikationen

text: Thrombocytopenia is the most common cause of bleeding tendency, and, if due to impaired platelet production, is best treated by platelet transfusions. Prophylactic transfusions for asymptomatic patients should be considered if platelet count is below 20000/μl. However, if bleeding occurs or surgery is inevitable, platelet count should be maintained above 50000/μl. The benefit of platelet transfusions has to be balanced against risks like fever, infections and haemolysis. The effectiveness of platelet transfusions should be examined after 1 and 24 hrs by measuring the corrected count increment (CCI). Not only alloimmunization is a reason for unsatisfactory platelet increments. A poor CCI can also be due to fever, sepsis, hepato-splenomegaly or special drugs, which must be taken into account when assessing the demand for platelet transfusions.


Mitteilungsseiten


title: Ultrastructural evidence for the localization of an indolealkylamine in supra-ependymal nerves from combined cytochemistry and pharmacology

text: Les terminaisons nerveuses supra-épendymales du rat ont été examinées au microscope électronique à l'aide de techniques cytochimiques et cytopharmacologiques. Il est apparu que les vésicules contenues dans ces terminaisons nerveuses renferment une indolealkylamine, très probablement de la 5-hydroxy-tryptamine.


title: Catching bird flu in a droplet

text: It is assumed that a timely mass administration of antiviral drugs, backed by quarantines and social distancing, could contain a nascent influenza epidemic at its source, provided that the first clusters of cases were localized within a short time. However, effective routine surveillance may be impossible in countries lacking basic public health resources. For a global containment strategy to be successful, low-cost, easy-to-use handheld units that permit decentralized testing would be vital. Here we present a microfluidic platform that can detect the highly pathogenic avian influenza virus H5N1 in a throat swab sample by using magnetic forces to manipulate a free droplet containing superparamagnetic particles. In a sequential process, the viral RNA is isolated, purified, preconcentrated by 50,000% and subjected to ultrafast real-time RT-PCR. Compared to commercially available tests, the bioassay is equally sensitive and is 440% faster and 2,000–5,000% cheaper. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1634) contains supplementary material, which is available to authorized users.


title: Bildgebende Diagnostik von Pneumonien

text: Pneumonia represents a disease with significant epidemiological, clinical and also economical relevance. Diagnostic imaging is important for detection, differentiation and follow up of pneumonic infiltration. However morphology of pulmonary infiltration is unspecific, even with computed tomography (CT). Therefore determination of the underlying agent with imaging is generally limited and non infectious differential diagnosis has to be considered. Knowledge of special manifestations, distribution patterns and differential diagnoses of pneumonic infiltrations and consideration of clinical aspects is essential to narrow differential diagnosis and spectrum of infectious agents. CT of the chest is particularly important in opportunistic infections and in patients under intensive medical treatment.


title: Infektionsassoziierte Hautblutungen

text: A broad spectrum of bacterial, viral, and parasitic infections is associated with hemorrhagic skin lesions, typically petechiae. The most prominent underlying entity is fulminant bacterial sepsis, which requires urgent and intensive treatment. In most cases, however, a self-limiting viral disease is the underlying cause. Thus, the pediatrician frequently encounters a diagnostic dilemma between timely diagnosis of sepsis and unnecessary invasive diagnostics. This article reviews the broad differential diagnosis and pathophysiology of infection-associated hemorrhagic skin lesions and proposes a diagnostic algorithm for the combination of fever and petechiae.


title: Genpolymorphismen beim Intensivpatienten: Ist der Krankheitsverlauf vorbestimmt?

text: Molecular biology has revolutionized medicine by increasing our understanding of the pathophysiological mechanisms of disease and the ability to assess genetic risk. Individual differences in disease manifestation and course in intensive care medicine often cannot be explained by known phenotypic risk factors alone. Recent data suggest an association between specific genotypes and the risk of adverse clinical outcomes. This includes inflammatory responses (i.e. TNF-α, Il-10), infectious diseases such as pneumonia or meningitis, sepsis, ARDS, as well as the mortality of critically injured patients (polytrauma, severe brain trauma). Continued identification of such allotypes and haplotypes may not only provide insight as to why the response to treatment varies amongst individuals in the intensive care unit, but also may potentially decrease morbidity and mortality through improved risk assessment and the administration of prophylactic therapy.


title: Cytomegalovirus infection in orthotopic liver transplantation

text: We retrospectively studied 175 orthotopic liver transplants in 151 patients. Of the 151 patients, 59 (39.1%) were diagnosed as having cytomegalovirus (CMV) infection. The rate of infection in patients treated for rejection was 48.8% as compared to 26.2% in patients without rejection (P<0.01). Antirejection therapy was associated with culture-positive cases in 33 out of 43 patients as compared to 9 out of 16 patients who had CMV antibody titer elevations. Patients were treated with gancyclovir if they had simultaneous positive cultures from multiple sites and were seriously ill. Eighteen of the 19 patients thus treated had side effects, one of which was serious (bone marrow hypoplasia). Cultures became negative in 15 out of 17 (88%) of the surviving patients. Patient survival was similar to our overall survival rate of 87%.


title: Hemikolektomie bei Kolonischämie: Fallbericht von Schweinegrippe mit letalem Verlauf

text: Pandemic influenza A (H1N1) virus infection is rapidly spreading and has also become a common problem in Germany. Many cases with severe clinical presentation and death have been documented, especially in persons with underlying medical conditions. As of December 15, 2009, Germany has reported 119 H1N1-associated deaths. We report here the first H1N1-associated death in Germany, a 36-year-old woman with morbid obesity. The patient underwent a laparotomy with colon resection due to colon ischemia, a rare visceral complication in such cases. In this article an attempt has been made to reflect the state of requirements in terms of safety, occupational health, hygiene and working conditions with respect to activities involving logistics in the diagnostics, treatment (also surgical) and handling of such patients. Given the rapidly evolving nature the outbreak of human infection with the novel influenza A (H1N1) virus, influenza vaccination is recommended as the only way to prevent the infection of health care workers and patients with underlying medical conditions.


Abstracts des 116. Internistenkongresses 2010


title: Endothelium function in sepsis

text: Endothelial cells can be the prime target for an infection and infected endothelial cells may serve as an initiating system for a systemic response as these cells are able to secrete many mediators known to be of paramount importance. Endothelial cell functions in turn are regulated by these circulating mediators. Cellular interactions with leukocytes revealed protective and destructive functions. Single cell and animal studies indicate that endothelial permeability is increased and apart from clinical obvious edema formation in septic patients, the endothelial component remains unknown. Endothelial coagulation activation has been shown in vitro, however human data supporting an endothelial procoagulatory state are lacking. Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies.