title: Is there a place for granulocyte colony-stimulating factor in non-neutropenic critically ill patients?

text: Immunoparalysis, characterised by impairments in neutrophil and monocyte/macrophage function, is common in critically ill patients. The theoretical ability of granulocyte colony-stimulating factor (G-CSF) to improve the functions of both neutrophils and monocytes/macrophages provides a rationale for G-CSF therapy in non-neutropenic critically ill patients with infection or a high risk of nosocomial infection. The expression of the receptors that mediate G-CSF effects in neutrophils and monocytes/macrophages is regulated by bacterial products, cytokines and endogenous G-CSF levels, accounting for the variables effects of G-CSF on the neutrophil functions of critically ill patients. This variability should be taken into account when designing studies on the use of G-CSF in ICU-patients. Studies are still needed to identify the subset of patients who may benefit from G-CSF therapy.


title: Blood filtration in children with severe sepsis: Safe adjunctive therapy

text: OBJECTIVE: To review the safety and efficacy of haemofiltration and plasmafiltration in children with severe sepsis. DESIGN: Retrospective case notes analysis. SETTING: University Paediatric Intensive Care Unit. PATIENTS: All children admitted to the intensive care unit between November 1985 and May 1992 with a primary diagnosis of severe sepsis who also received blood filtration therapy. INTERVENTIONS: Continuous haemofiltration (HF) 18 patients; continuous haemofiltration and plasmafiltration (PF) 9 patients. MEASUREMENTS AND RESULTS: 27 children with sepsis-induced MOSF, median age 26.6 months (range 0.33–185), median weight 12 kg (range 2.5–58), mean PRISM score 19.4 (SD 8.6), mean number of organs failing 2.78 (SD 0.9) received filtration for a median duration of 36 hours (range 2–145). Eight (30%) survived (HF5/18, PF3/9). There was no significant difference in the demographic features between the HF group and the PF group and no difference in mortality. The two groups were pooled to assess the effect of commencement of filtration on clinical wellbeing. Arterial blood gases, electrolytes, full blood examination, ventilator settings and doses of inotropes were recorded immediately prior to commencement of filtration and 18 h after commencement. Serum anion gap and osmolality were calculated using conventional formulae. There were no significant changes in the level of cardiorespiratory support, or biochemical markers of severity following commencement of filtration. Platelet count fell 32% (p=0.029) but no bleeding was encountered. No severe complications were observed during 1222 h of filtration. No bleeding or infection was observed at the site of cannulation. One child developed haemodynamic instability following commencement of plasmafiltration necessitating abandonment of the procedure. CONCLUSION: Haemofiltration or plasmafiltration can be performed safely in children with severe sepsis but their effect on outcome remains unknown.


title: Pandemics: avoiding the mistakes of 1918

text: As bodies piled up, the United States' response to the 'Spanish flu' was to tell the public that there was no cause for alarm. The authority figures who glossed over the truth lost their credibility, says John M. Barry.


title: Making it big in Taiwan

text: This small but inventive island is putting transgenics and nanotechnology to novel uses. A pay rise might be all it needs to lure its expatriate scientists home, says Paul Smaglik.


Blood ferritin and isoferritins measurements may be helpful in acute respiratory distress syndrome patients


Acute respiratory distress syndrome secondary to human metapneumovirus infection in a young healthy adult


title: Plan to pool bird-flu data takes off

text: Researchers welcome bid to share resources.


title: Assessing predictive accuracy for outcomes of ventilator-associated events in an international cohort: the EUVAE study

text: PURPOSE: To analyze the impact on patient outcome of ventilator-associated events (VAEs) as defined by the Centers for Disease Control and Prevention (CDC) in 2008, 2013, and the correlation with ventilator-associated pneumonia (VAP) or tracheobronchitis (VAT). METHODS: This was a prospective, observational, multicenter, international study conducted at 13 intensive care units (ICUs); thirty consecutive adults mechanically ventilated for ≥ 48 h per site were eligible, with daily follow-up being recorded in a collaborative web database; VAEs were assessed using the 2013 CDC classification and its 2015 update. RESULTS: A total of 2856 ventilator days in 244 patients were analyzed, identifying 33 VAP and 51 VAT episodes; 30-day ICU mortality was significantly higher (42.8 vs. 19.6%, p < 0.007) in patients with VAP than in those with VAT. According to the 2013 CDC definitions, 117 VAEs were identified: 113 (96%) were infection-related ventilator-associated complication-plus (IVAC-plus), while possible ventilator-associated pneumonia (PVAP) was found in 64 (56.6%) of them. VAE increased the number of ventilator days and prolonged ICU and hospital LOS (by 5, 11, and 12 days, respectively), with a trend towards increased 30-day mortality (43 vs 28%, p = 0.06). Most episodes (26, 55%) classified as IVAC-plus without PVAP criteria were due to atelectasis. PVAP significantly increased (p < 0.05) ventilator days as well as ICU and hospital LOS (by 10.5, 14, and 13 days, respectively). Only 24 (72.7%) of VAP and 15 (29.4%) of VAT episodes met IVAC-plus criteria. CONCLUSIONS: Respiratory infections (mainly VAT) were the most common complication. VAE algorithms only identified events with surrogates of severe oxygenation deterioration. As a consequence, IVAC definitions missed one fourth of the episodes of VAP and three fourths of the episodes of VAT. Identifying VAT (often missed by IVAC-plus criteria) is important, as VAP and VAT have different impacts on mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-018-5269-7) contains supplementary material, which is available to authorized users.


title: Klaus Stöhr, director of the influenza vaccine franchises, Novartis Vaccines and Diagnostics, Cambridge, Massachusetts

text: Klaus Stöhr moves from the WHO to industry.


docid: kngjiagf

title: Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP

text: THE photoreceptor G protein, transducin, is one of the class of heterotrimeric G proteins that mediates between membrane receptors and intracellular enzymes or ion channels. Light-activated rhodopsin catalyses the exchange of GDP for GTP on multiple transducin molecules. Activated transducin then stimulates cyclic GMP phosphodiesterase by releasing an inhibitory action of the phosphodiesterase γ-subunits. This leads to a decrease in cGMP levels in the rod, and closure of plasma membrane cationic channels gated by cGMP(1–4). In this and other systems, turn-off of the response requires the GTP bound to G protein to be hydrolysed by an intrinsic GTPase activity(5–7). Here we report that the interaction of transducin with cGMP phosphodiesterase, specifically with its γ-subunits, accelerates GTPase activity by several fold. Thus the γ-subunits of the phosphodiesterase serve a function analogous to the GTPase-activating proteins that regulate the class of small GTP-binding proteins. The acceleration can be partially suppressed by cGMP, most probably through the non-catalytic cGMP-binding sites of phosphodiesterase α and β-subunits. This cGMP regulation may function in light-adaptation of the photo-response as a negative feedback that decreases the lifetime of activated cGMP phosphodiesterase as light causes decreases in cytoplasmic cGMP.


title: Differential tropism of human herpesvirus 6 (HHV-6) variants and induction of latency by HHV-6A in oligodendrocytes

text: Human herpesvirus 6 (HHV-6) is a ubiquitous β-herpesvirus associated with a number of clinical disorders. Two closely but biologically distinct variants have been described. HHV-6 variant B causes the common childhood disease exhanthem subitum, and although the pathologic characteristics for HHV-6 variant A are less well defined, HHV-6A has been suggested to be more neurotropic. We studied the effect of both HHV-6 variants in an oligodendrocyte cell line (MO3.13). Infection of M03.13 was monitored by cytopathic effect (CPE), quantitative TaqMan PCR for viral DNA in cells and supernatant, reverse transcriptase-polymerase chain reaction (RT-PCR) to detect viral RNA, and indirect immunofluorescence (IFA) to detect viral protein expression. HHV-6A infection induced significantly more CPE than infection with HHV-6B. HHV-6B induced an abortive infection associated with a decrease of the initial viral DNA load over time, early RNA expression, and no expression of viral antigen. In contrast, infection with HHV-6A DNA persisted in cells for at least 62 days. During the acute phase of infection with HHV-6A, intracellular and extracellular viral load increased and cells expressed the viral protein IE-2 and gp116/54/64. No HHV-6A RNA or protein was expressed after 30 days post infection, suggesting that HHV-6A formed a latent infection. These studies provide in vitro support to the hypothesis that HHV-6 can actively infect oligodendrocytes. Our results suggest that HHV-6A and HHV-6B have different tropism in MO3.13 cells and that an initially active HHV-6A infection can develop latency. Differences between HHV-6A and -6B infection in different neural cell types may be associated with different neurological diseases.


2nd World Congress on Pediatric Intensive Care 1996 Rotterdam, The Netherlands, 23–26 June 1996 Abstracts of Oral Presentations, Posters and Nursing Programme


What’s new in invasive pulmonary aspergillosis in the critically ill


Sidelines


title: Growth hormone does not affect albumin synthesis in the critically ill

text: Objective: To study the effect of growth hormone (GH) on albumin synthesis in critically ill patients. Design: Prospective randomized controlled study. Setting: Two intensive care units, university hospital and county hospital, respectively. Patients: Twenty-two critically ill patients in the intensive care unit. Interventions: Albumin synthesis was measured twice in each patient, with a 5-day interval. The patients in the control group (n=11) received standard intensive care unit (ICU) treatment between measurements, whereas those in the GH group (n=11) also received 0.3 U/kg daily of human recombinant GH. Measurements and results: Albumin synthesis was measured by labeling with L-[(2)H(5)]phenylalanine. In the control group, the fractional synthesis rate (FSR) of albumin was 16.3±4.1%/day (mean and SD) in the first measurement and 15.7±4.2%/day 5 days later (NS), whereas in the GH group the corresponding values were 17.0±4.7%/day and 16.7±5.5%/day (NS). The calculated absolute synthesis rates of albumin, based on FSR and intravascular albumin mass, also showed no effect of GH. Conclusion: Albumin synthesis rates were consistently higher in the two groups of critically ill patients than previously reported values in healthy subjects. However, GH treatment for 5 days neither stimulated nor inhibited albumin synthesis rates in these critically ill patients.


title: Antithrombin III for critically ill patients: a systematic review with meta-analysis and trial sequential analysis

text: PURPOSE: Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. METHODS: We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language. RESULTS: We included 30 RCTs with a total of 3933 participants. The majority of included trials were at high risk of bias. Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality (RR 0.95, 95 % CI 0.88–1.03, I (2) = 0 %, fixed-effect model, 29 trials, 3882 participants). Among those with severe sepsis and disseminated intravascular coagulation (DIC), AT III showed no impact on mortality (RR 0.95, 95 % Cl 0.88–1.03, I (2) = 0 %, fixed-effect model, 12 trials, 2858 participants). We carried out multiple subgroup and sensitivity analyses to assess the benefits and harms of AT III and to examine the impact of risk of bias. AT III significantly increased bleeding events (RR 1.58, 95 % CI 1.35–1.84, I (2) = 0 %, fixed-effect model, 11 trials, 3019 participants). However, for all other outcome measures and analyses, the results did not reach statistical significance. CONCLUSIONS: There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC. AT III did not show an impact on mortality, but increased the risk of bleeding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-016-4225-7) contains supplementary material, which is available to authorized users.


title: Tumour necrosis factor α stimulates resorption and inhibits synthesis of proteoglycan in cartilage

text: During inflammatory reactions, activated leukocytes are thought to produce a variety of small proteins (cytokines) that influence the behaviour of other cells (including other leukocytes). Of these substances, which include the interleukins, interferons and tumour necrosis factors (TNFs), interleukin-1 (IL-1) has been considered potentially a most important inflammatory mediator because of its wide range of effects (reviewed in refs 1, 2). In vivo it is pyrogenic and promotes the acute phase response; in vitro it activates lymphocytes(3) and stimulates resorption of cartilage(4) and bone(5,6). Cartilage resorption is a major feature of inflammatory diseases such as rheumatoid arthritis, and IL-1 is the only cytokine hitherto known to promote it. TNFs are characterized by their effects on tumours and cytotoxicity to transformed cells(7–9), but share some actions with IL-1.1 report here that recombinant human TNFα stimulates resorption and inhibits synthesis of proteoglycan in explants of cartilage. Its action is similar to and additive with IL-1, and it is a second macrophage-derived cytokine whose production in rheumatoid arthritis, or inflammation generally, could contribute to tissue destruction.


title: Dengue and malaria infections in pregnancy: Maternal, fetal and neonatal outcomes at a tertiary care hospital

text: BACKGROUND: Malaria and dengue cause major morbidity in developing nations and are more severe in pregnancy. Maternal, fetal, and neonatal outcomes in pregnant patients infected with dengue or malaria were studied. METHODS: The medical records of pregnant women admitted with either dengue or malaria infections from 2011–2015 to this hospital were reviewed. Clinical outcomes and laboratory tests were examined. RESULTS: Of 85 women, 56%, 21%, and 22% had contracted dengue, malaria, and multiple infections, respectively. Pregnant women who had contracted dengue fever alone were more likely to present to the hospital at an earlier gestational age (24 weeks, p = 0.03). Women with multiple infections, were more likely to deliver earlier (30 weeks, p < 0.01). Women with malaria were more likely to have low birth weight deliveries (mean birth weight 2394 g, p = 0.03). The incidence of in-hospital deaths among the cohort was 7%. CONCLUSION: It is imperative to develop guidelines to screen for and diagnose dengue and malaria in pregnancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00508-019-01606-8) contains supplementary material, which is available to authorized users.


Early application of high frequency oscillatory ventilation in ‘H1N1 influenza’ related ARDS is associated with better outcome: a retrospective study


title: Apparent discontinuous transcription of Trypanosoma brucei variant surface antigen genes

text: The repeated mini-exon sequence that encodes the first 35 base pairs of all variant surface antigen mRNAs of Trypanosoma brucei directs the synthesis of a discrete 137-nucleotide transcript. It thus seems that variant surface antigen mRNAs are transcribed discontinuously, and we present two alternative models for how this might occur.


Early steroid therapy for patients with H1N1 influenza A virus infection


title: The rise of the urbanite

text: From their earliest beginnings, cities have brought both benefits and risks to the health of their inhabitants. Although some of the hazards have been banished, others remain — and new ones have emerged. By Stephanie Pain


title: Treatment with bovine surfactant in severe acute respiratory distress syndrome in children: a randomized multicenter study

text: OBJECTIVE: To determine whether bovine surfactant given in cases of severe pediatric acute respiratory distress syndrome (ARDS) improves oxygenation. DESIGN: Single-center study with 19 patients, followed by a multicenter randomized comparison of surfactant with a standardized treatment algorithm. Primary endpoint PaO(2)/FIO(2) at 48 h, secondary endpoints: PaO(2)/FIO(2) at 2, 4, 12, and 24 h, survival, survival without rescue, days on ventilator, subgroups analyzed by analysis of variance to identify patients who might benefit from surfactant SETTING: Multicenter study in 19 reference centers for ARDS. PATIENTS: Children after the 44th postconceptional week and under 14 years old, admitted for at least 4 h, ventilated for 12–120 h, and without heart failure or chronic lung disease. In the multicenter study 35 patients were recruited; 20 were randomized to the surfactant group and 15 to the nonsurfactant group. Decreasing recruitment of patients led to a preliminary end of this study. INTERVENTIONS: Administration of 100 mg/kg bovine surfactant intratracheally under continuous ventilation and PEEP, as soon as the PaO(2)/FIO(2) ratio dropped to less than 100 for 2 h (in the pilot study increments of 50 mg/kg as long as the PaO(2)/FIO(2) did not increase by 20%). A second equivalent dose within 48 h was permitted. RESULTS: In the pilot study the PaO(2)/FIO(2) increased by a mean of 100 at 48 h (n=19). A higher PaO(2)/FIO(2) ratio was observed in the surfactant group 2 h after the first dose (58 from baseline vs. 9), at 48 h there was a trend towards a higher ratio (38 from baseline vs. 22). The rate of rescue therapy was significantly lower in the surfactant group. Outcome criteria were not affected by a second surfactant dose (n=11). A significant difference in PaO(2)/FIO(2) in favor of surfactant at 48 h was found in the subgroup with an initial PaO(2)/FIO(2) ratio higher than 65 and in patients without pneumonia. CONCLUSIONS: Surfactant therapy in severe ARDS improves oxygenation immediately after administration. This improvement is sustained only in the subgroup of patients without pneumonia and that with an initial PaO(2)/FIO(2) ratio higher than 65


title: Ventilator-associated pneumonia: present understanding and ongoing debates

text: INTRODUCTION: Ventilator-associated pneumonia (VAP) is a common cause of nosocomial infection, and is related to significant utilization of health-care resources. In the past decade, new data have emerged about VAP epidemiology, diagnosis, treatment and prevention. RESULTS: Classifying VAP strictly based on time since hospitalization (early- and late-onset VAP) can potentially result in undertreatment of drug-resistant organisms in ICUs with a high rate of drug resistance, and overtreatment for patients not infected with resistant pathogens. A combined strategy incorporating diagnostic scoring systems, such as the Clinical Pulmonary Infection Score (CPIS), and either a quantitative or qualitative microbiological specimen, plus serial measurement of biomarkers, leads to responsible antimicrobial stewardship. The newly proposed ventilator-associated events (VAE) surveillance definition, endorsed by the Centers for Disease Control and Prevention, has low sensitivity and specificity for diagnosing VAP and the ability to prevent VAE is uncertain, making it a questionable surrogate for the quality of ICU care. The use of adjunctive aerosolized antibiotic treatment can provide high pulmonary concentrations of the drug and may facilitate shorter durations of therapy for multi-drug-resistant pathogens. A group of preventive strategies grouped as a ‘ventilator bundle’ can decrease VAP rates, but not to zero, and several recent studies show that there are potential barriers to implementation of these prevention strategies. CONCLUSION: The morbidity and mortality related to VAP remain high and, in the absence of a gold standard test for diagnosis, suspected VAP patients should be started on antibiotics based on recommendations per the 2005 ATS guidelines and knowledge of local antibiotic susceptibility patterns. Using a combination of clinical severity scores, biomarkers, and cultures might help with reducing the duration of therapy and achieving antibiotic de-escalation.


title: Flu researchers slam US agency for hoarding data

text: Better sharing of information would help vaccine design.


title: Emerging zoonotic encephalitis viruses: Lessons from Southeast Asia and Oceania

text: The last decade of the 20th Century saw the introduction of an unprecedented number of encephalitic viruses emerge or spread in the Southeast Asian and Western Pacific regions (Mackenzie et al, 2001; Solomon, 2003a). Most of these viruses are zoonotic, either being arthropod-borne viruses or bat-borne viruses. Thus Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has spread through the Indonesian archipelago to Papua New Guinea (PNG) and to the islands of the Torres Strait of northern Australia, to Pakistan, and to new areas in the Indian subcontinent; a strain of tick-borne encephalitis virus (TBEV) was described for the first time in Hokkaido, Japan; and a novel mosquito-borne alphavirus, Me Tri virus, was described from Vietnam. Three novel bat-borne viruses emerged in Australia and Malaysia; two, Hendra and Nipah viruses, represent the first examples of a new genus in the family Paramyxoviridae, the genus Henipaviruses, and the third, Australian bat lyssavirus (ABLV) is new lyssavirus closely related to classical rabies virus. These viruses will form the body of this brief review.


Corticosteroids do not cause harmful increase of viral load in severe H1N1 virus infection


H1N1-related ARDS requiring veno-venous extracorporeal membrane oxygenation and the heart


title: Dimensions of superspreading

text: Analyses of contact-tracing data on the spread of infectious disease, combined with mathematical models, show that control measures require better knowledge of variability in individual infectiousness.


title: Mechanical ventilation alters the immune response in children without lung pathology

text: Objective: This study was undertaken to examine the hypothesis that mechanical ventilation in association with anesthesia would alter the cytokine profile in infants without preexisting lung pathology. Design and setting: Prospective observational study in pediatric intensive care unit in a university hospital. Patients: Twelve infants who were subjected to an uncomplicated diagnostic cardiac catheterization procedure were studied. All subjects were ventilated with a volume control mode, 0.3 FIO(2), 4 cmH(2)O PEEP, and 10 ml/kg tidal volume. Volatile (servoflurane) anesthetics were given. Measurements and results: Tracheal aspirates and blood samples were obtained before and after 2 h of mechanical ventilation. In tracheal aspirates and in supernatants of stimulated whole-blood cultures cytokine concentrations were measured. In the tracheal aspirates the immune balance was characterized by a proinflammatory response pattern, with a significant increase in TNF-α and IL-6 concentrations; concentrations of anti-inflammatory mediators remained very low. The functional capacity of peripheral blood leukocytes to produce INF-γ, TNF-α, and IL-6 in vitro was significantly decreased. This was accompanied by a significant decrease in the killing activity of natural killer cells. Conclusions: Two hours of servoflurane and mechanical ventilation using a tidal volume of 10 ml/kg is associated with remarkable changes in the immune response in infants without preexisting lung pathology undergoing cardiac catheterization. In the lungs the immune balance favors a proinflammatory response pattern without detectable concentrations of anti-inflammatory mediators. The Th1 immune response by peripheral blood leukocytes was decreased. The observed change in Th1/Th2 balance in favor of Th2 cytokine activity may be a systemic adaptation to the proinflammatory milieu in the lung.


OP 001-035


title: Structure of the parainfluenza virus 5 F protein in its metastable, prefusion conformation

text: Enveloped viruses have evolved complex glycoprotein machinery that drives the fusion of viral and cellular membranes, permitting entry of the viral genome into the cell. For the paramyxoviruses, the fusion (F) protein catalyses this membrane merger and entry step, and it has been postulated that the F protein undergoes complex refolding during this process. Here we report the crystal structure of the parainfluenza virus 5 F protein in its prefusion conformation, stabilized by the addition of a carboxy-terminal trimerization domain. The structure of the F protein shows that there are profound conformational differences between the pre- and postfusion states, involving transformations in secondary and tertiary structure. The positions and structural transitions of key parts of the fusion machinery, including the hydrophobic fusion peptide and two helical heptad repeat regions, clarify the mechanism of membrane fusion mediated by the F protein. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature04322) contains supplementary material, which is available to authorized users.


title: Multiple organ failure and coma as initial presentation of pheochromocytoma in a patient with multiple endocrine neoplasia (MEN) type II A

text: The unusual case of a 65-year-old woman with intermittent hypotension, fever, pulmonary edema and coma as initial presentation of pheochromocytoma is reported. The patient developed respiratory, cardiac and renal failure, disseminated intravascular coagulation and liver dysfunction. She, had to be defibrillated on multiple occasions, occurring in periods of severe hypertension. After successful surgical removal of a pheochromocytoma a thyroid medullary carcinoma was detected. Several members of the patients family had presented with multiple endocrine neoplasia (MEN II).


title: Molecular targeted therapy-related life-threatening toxicity in patients with malignancies. A systematic review of published cases

text: BACKGROUND: Molecular targeted therapy increased overall and disease-free survival in a wide range of malignancies. Although generally well tolerated compared to chemotherapy, molecular targeted therapy may be associated with adverse events requiring ICU admission. Informing clinicians about clinical features of these toxic events might maintain awareness and favor early recognition, prompt diagnosis and treatment. METHODS: We performed a systematic review of published case reports of molecular targeted therapy-related life-threatening toxicity that led to ICU admission. The search used the Pubmed database using medical subject heading (Mesh) terms, including all FDA-approved molecular targeted therapy (TT), up to March 2019. No language restriction was applied. All cases reports of patients admitted to the ICU for molecular targeted therapy-related toxicity were included. Non-FDA-approved combinations of treatments or hormonal therapy were not included. RESULTS: Two hundred and fifty-three cases were identified. Nearly half of them (n = 102; 40.3%) were related to anti-angiogenic agents, mostly for gastrointestinal and cardiovascular complications. Other molecules responsible for adverse events were chiefly immune checkpoint inhibitors (n = 85, 33.6%), EGFR inhibitors (n = 33; 13.0%), and anti-HER2 (n = 10; 4.0%). They were associated with adverse events such as respiratory or hypersensitivity events. Management and outcomes associated with these life-threatening complications are reported. CONCLUSIONS: Based on the vast number of treated patients, only 253 cases of molecular therapy-related severe toxicity are reported in cancer patients. Symptoms and biomarkers that depict these events need to be better identified as to allow appropriate reporting and improving dose and schedule of the treatment adapted to each patient. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05650-w) contains supplementary material, which is available to authorized users.


title: Liver inflammation and acute respiratory distress syndrome in a patient receiving hepatitis B vaccine: a possible relationship?

text: We describe a patient in whom clinical evidence of liver and lung dysfunction developed after he received the second dose of recombinant hepatitis B vaccine, despite no serologic evidence of viral hepatitis. However, liver biopsy specimens demonstrated both surface antigens and core antigens, possibly indicating silent hepatitis B virus infection. A search for an infective etiology for the patient’s subsequent clinical deterioration in lung function did not yield pathogens; postmortem examination revealed evidence of immune complex-mediated organ injury in the liver, lungs, and kidneys.


title: Endothelial protein C receptor polymorphisms and risk of severe sepsis in critically ill patients

text: PURPOSE: Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients. METHODS: Three polymorphisms in the EPCR gene were genotyped in 389 Caucasian critically ill patients, hospitalized in the intensive care units of two major hospitals in Athens, Greece. Multivariate logistic regression analysis controlling for age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the development of SS/SS. RESULTS: H2 carriers versus all other genotypes combined had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8 % of critically ill patients carrying minor alleles belonging to both H1 and H3 haplotypes, in 58.0 % of H1 carriers, 64.3 % of H3 carriers, and 65.2 % of patients carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR) for developing SS/SS were 0.34 [95 % confidence interval (CI) 0.16–0.76, p = 0.008] for simultaneous H1 and H3 carriers, 0.65 (95 % CI 0.37–1.13, p = 0.123) for H1 carriers, and 0.82 (95 % CI 0.39–1.70, p = 0.590) for H3 carriers. CONCLUSIONS: Our results indicate that simultaneous carriers of minor alleles belonging to both the H1 and H3 haplotypes may be at reduced risk of developing SS/SS in this cohort of critically ill patients.


Severe community-acquired pneumonia caused by Panton-Valentine leukocidin-positive Staphylococcus aureus: first reported case in the United Kingdom


title: Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions

text: RATIONALE: The standard of care for patients with acute respiratory distress syndrome (ARDS) has been developed based on studies that usually excluded patients with major comorbidities. OBJECTIVES: To describe treatments and outcomes according to comorbidities in patients with ARDS admitted to 19 ICUs (1997–2014). METHODS: Patients were grouped based on comorbidities. Determinants of day-28 mortality were identified by multivariable Cox analysis stratified on center. MEASUREMENTS AND MAIN RESULTS: Among 4953 ARDS patients, 2545 (51.4%) had major comorbidities; the proportion with major comorbidities increased after 2008. Hematological malignancy was associated with severe ARDS and rescue therapies for refractory hypoxemia. COPD, HIV infection, and hematological malignancy were associated with a lower likelihood of invasive mechanical ventilation on the admission day. Admission-day SOFA score was higher in patients with major comorbidities, who more often received vasopressors, dialysis, or treatment-limitation decisions. Day-28 mortality was 33.7% overall, 27.2% in patients without major comorbidities, and 31.1% (COPD) to 56% (hematological malignancy) in patients with major comorbidities. By multivariable analysis, mortality was lower in patients with COPD and higher in those with chronic heart failure, solid tumors, or hematological malignancies. Mortality was independently associated with P(a)O(2)/F(i)O(2) and PaCO(2) on day 1, ARDS of pulmonary origin, worse SOFA score, and ICU-acquired events. CONCLUSIONS: Half the patients with ARDS had major comorbidities, which were associated with severe ARDS, multiple organ dysfunction, and day-28 mortality. These findings do not support the exclusion of ARDS patients with severe comorbidities from randomized clinical trials. Trials in ARDS patients with whatever comorbidities are warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-018-5209-6) contains supplementary material, which is available to authorized users.


title: Safety of tracheotomy in neutropenic patients: A retrospective study of 26 consecutive cases

text: OBJECTIVE: To evaluate the safety of tracheotomy in neutropenic ventilated cancer patients, in terms of infectious and haemorrhagic complications. DESIGN: Retrospective study. SETTING: A medical-surgical intensive care unit in a Cancer-hospital.Patients and participants: 26 consecutive patients undergoing a tracheotomy in neutropenic period, from 1987 to 1990. INTERVENTIONS: Tracheotomy, performed at the bedside or in operating, room. MEASUREMENTS AND RESULTS: In all neutropenic patients undergoing a tracheotomy, the characteristics and duration of both neutropenia and mechanical ventilation have been recorded. Stomal bleeding and infection, and infectious pneumonias and alveolar haemorrhage have been carefully reviewed. Platelets were transfused in 23 of the 26 patients at the time of the procedure; no local haemorrhage was observed. Neither stomal nor pulmonary infections secondary to traceotomy were noted. No respiratory worsening was attributable to the tracheotomy. Nineteen patients (73%) died in ICU, without direct link between tracheotomy and death. CONCLUSIONS: These findings suggest that a tracheotomy can be safely performed in neutropenic patients requiring mechanical ventilation.


title: Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study

text: Objective: To evaluate the incidence, clinical features, and prognosis of pulmonary complications associated with toxic epidermal necrolysis Design: Prospective study. Setting: Dermatology intensive care unit in Mondor Hospital, France. Patients: 41 consecutive patients. Interventions: On admission, then daily, respiratory evaluation was based on clinical examination, chest X-ray, and arterial blood gas analysis. When clinical symptoms, X-ray abnormalities, or hypoxemia [partial pressure of oxygen (PO(2))<80 mm Hg] were present, fiberoptic bronchoscopy was performed. Results: 10 patients presented early manifestations: dyspnea (n=10), bronchial hypersecretion (n=7), marked hypoxemia (n=10) (PO(2)=59 ± 8 mmHg). Chest X-ray was normal (n = 8) or showed interstitial infiltrates (n=2). In these 10 patients, fiberoptic bronchoscopy demonstrated sloughing of bronchial epithelium in proximal airways. Delayed pulmonary complications occurred in 6 of these 10 patients from day 7 to day 15: pulmonary edema (n=2), atelectasis (n=1), bacterial pneumonitis (n=4). Mechanical ventilation was required in 9 patients. A fatal outcome occurred in 7 patients. Seven patients did not develop early pulmonary manifestations (PO(2) on admission 87 ± 6 mm Hg) but only delayed pulmonary symptoms related to atelectasis (n=1), pulmonary edema (n=4), and bacterial pneumonitis (n=3); bronchial epithelial detachment was not observed. None of them required mechanical ventilation and all recovered with appropriate therapy. Conclusions: “Specific” involvement of bronchial epithelium was noted in 27 % of cases and must be suspected when dyspnea, bronchial hypersecretion, normal chest X-ray, and marked hypoxemia are present during the early stages of toxic epidermal necrosis. Bronchial injury seems to indicate a poor prognosis, as mechanical ventilation was required for most of these patients and was associated with a high mortality.


title: Influence of positive end-expiratory pressure (PEEP) on histopathological and bacteriological aspects of pneumonia during low tidal volume mechanical ventilation

text: OBJECTIVE: Ventilatory strategies combining low tidal volume (V(T)) with positive end-expiratory pressure (PEEP) are considered to be lung protective. The influence of the PEEP level was investigated on bacteriology and histology in a model of ventilator-associated pneumonia. SUBJECTS: Nineteen New Zealand rabbits. INTERVENTIONS: The animals were mechanically ventilated with a positive inspiratory pressure of 15 cmH(2)O and received either a zero end-expiratory pressure (ZEEP, n=6), a 5 cmH(2)O PEEP (n=5) or a 10 cmH(2)O PEEP (n=4). An inoculum of Enterobacter aerogenes was then instilled intrabronchially. The non-ventilated pneumonia group (n=4) was composed of spontaneously breathing animals which received the same inoculum. Pneumonia was assessed 24 h later. MAIN RESULTS: The lung bacterial burden was higher in mechanically ventilated animals compared with spontaneously breathing animals. All animals from the latter group had negative spleen cultures. The spleen bacterial concentration was found to be lower in the 5 cmH(2)O PEEP group when compared to the ZEEP and 10 cmH(2)O PEEP groups (3.1±1.5 vs 4.9±1.1 and 5.0±1.3 log(10) cfu/g, respectively; p<0.05). Lung weight and histological score values were lower in the spontaneously breathing animals as well as in the 5 cmH(2)O PEEP group compared with the ZEEP and 10 cmH(2)O groups. CONCLUSIONS: Mechanical ventilation substantially increased the lung bacterial burden and worsened the histological aspects of pneumonia in this rabbit model. Variations in terms of lung injury and systemic spreading of infection were noted with respect to the ventilatory strategy.


title: Cytomegalovirus reactivation in ICU patients

text: INTRODUCTION: Approximately 20 years have passed since we reported our results of histologically proven cytomegalovirus (CMV) pneumonia in non-immunocompromised ICU patients. Even if there are more recent reports suggesting that CMV may worsen the outcomes for ICU patients, there is no definite answer to this question: is CMV a potential pathogen for ICU patients or is it simply a bystander? METHODS: We will describe the pathophysiology of active CMV infection and the most recent insights concerning the epidemiological aspects of these reactivations. MAJOR FINDINGS: Cytomegalovirus can be pathogenic by a direct organ insult (such as for the lung), by decreasing host defences against other microorganisms and/or by enhancing the body’s inflammatory response (as in acute respiratory distress syndrome). The incidence of active CMV infection is dependent on the diagnostic method used. Using the most sophisticated available biological tools, the incidence can reach 15–20 % of ICU patients (20–40 % in ICU patients with positive CMV serology). In adequately powered cohorts of patients, active CMV infection appears to be associated with worse outcomes for mechanically ventilated ICU patients. DISCUSSION: There is no absolute direct proof of a negative impact of active CMV infection on the health outcomes of mechanically ventilated patients. Prospective randomized trials are lacking. Future trials should examine the potential benefits for health outcomes of using antiviral treatments. Such treatments could be prophylactic, pre-emptive or used only when there is an end-organ disease. CONCLUSION: Cytomegalovirus infection may affect health outcomes for ICU patients. Additional prospective trials are necessary to confirm this hypothesis.


docid: ijrghpco

title: Climate change, global warming, and intensive care


title: A global call for new polio vaccines

text: The end is near but eradication will not be as simple as once thought.


title: How safe is non-bronchoscopic bronchoalveolar lavage in critically ill mechanically ventilated children?

text: Objective: To assess the safety of non-bronchoscopic bronchoalveolar lavage (NB-BAL) in critically ill mechanically ventilated children. Setting: Paediatric intensive care unit in a tertiary children's hospital. Methods: The data from 60 consecutive critically ill mechanically ventilated children who underwent NB-BAL was reviewed from November 1997 to December 1999. PRISM score prior to NB-BAL, observations at the time of NB-BAL and arterial blood gases, oxygenation index (OI), ventilator settings, haemodynamic variables and temperature taken at 1 h before, and 1 and 6 h after NB-BAL, were retrieved from the archived computerised database. Results: Median age was 7 months (IQR 2.8–43 months) and median weight was 5.5 kg (IQR 4–14 kg). Four (7%) patients exhibited significant immediate complications, requiring escalation of respiratory or haemodynamic support. Forty-two (70%) patients had complete data for calculation of OI; there was no significant change in median OI at 1 and 6 h after NB-BAL. However 5 (12%) of these patients experienced an increase in OI of between 10 and 45 at 1 h post NB-BAL, which returned to baseline at 6 h post NB-BAL. Complications did not correlate with any of the available variables: baseline OI, PRISM score or with deterioration at the time of the procedure, although it was observed that four out of the six patients with baseline OIs of greater than 20 experienced complications. Conclusion: Non-bronchoscopic bronchoalveolar lavage in critically ill mechanically ventilated neonates and children is generally a well-tolerated procedure, but for some patients, in whom it was not possible to elucidate predictive factors, complications developed. All patients, particularly those with OIs of greater than 20, require careful monitoring during and after the procedure.


title: Containing risk

text: The ad-hoc proliferation of high-security biological labs must be controlled, and should be tied in more closely to broader research and public-health goals.


Information on critical issues related to infection control presented during the Eighth Conference on Infectious Diseases: Monday, Dec 8, to Wednesday, Dec 10, 2003


title: Decreasing Latitude and Increasing Regulation in Transplantable Tissue Programs

text: • ADVANCED TECHNOLOGY and improved surgical techniques have led to new therapeutic uses for allografts. • DISEASE TRANSMISSION via allograft tissue transplants has prompted federal intervention in the tissue banking industry and resulted in federal regulations. • NEW STANDARDS from the Joint Commission on Accreditation of Healthcare Organizations became effective July 1,2005, and apply to all hospitals that store or implant allograft tissues. These standards include mandatory policies on all aspects of hospital transplantation programs, including tissue ordering, receipt, storage, issuance, and record keeping. AORN J 82 (November 2005) 806–814.


Reliability of brain death diagnostics


Safety resources for perioperative clinicians


title: Multiple Sclerosis: Basic Concepts and Hypothesis

text: Multiple sclerosis, an inflammatory disease of the central nervous system, is characterized by primary destruction of myelin. This review covers recent advances in neuropathology, immunogenetics, neuroimmunology, and neurovirology that have provided insights regarding its pathogenesis. Three hypotheses are discussed: (1) autoimmunity, (2) “bystander” demyelination, and (3) immune destruction of persistently infected oligodendrocytes. A paradigm for induction of primary demyelination is proposed in which immune cells recognize “foreign” antigens on the surface of oligodendrocytes in the context of major histocompatibility complex gene products. The final result of this scheme may be “dying-back gliopathy,” the alteration being noted first in the most distal extension of the oligodendrocyte—that is, the myelin sheaths.


title: Overexpression of pulmonary extracellular superoxide dismutase attenuates endotoxin-induced acute lung injury

text: PURPOSE: Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of superoxide dismutase (EC-SOD) to reduce the severity of endotoxin-induced lung injury. METHODS: Animals were randomly allocated to undergo intratracheal instillation of (1) surfactant alone (vehicle); (2) adeno-associated virus (AAV) vectors containing a null transgene (AAV-null); and (3) adeno-associated virus vectors containing the EC-SOD transgene (AAV-EC-SOD) and endotoxin was subsequently administered intratracheally. Two additional groups were randomized to receive (1) vehicle or (2) AAV-EC-SOD, and to undergo sham (vehicle) injury. The severity of the lung injury was assessed in all animals 24 h later. RESULTS: Endotoxin produced a severe lung injury compared to sham injury. The AAV vector encoding EC-SOD increased lung EC-SOD concentrations, and enhanced the antioxidant capacity of the lung. EC-SOD overexpression decreased the severity of endotoxin-induced ALI, reducing the decrement in systemic oxygenation and lung compliance, decreasing lung permeability and decreasing histologic injury. EC-SOD attenuated pulmonary inflammation, decreased bronchoalveolar lavage neutrophil counts, and reduced interleukin-6 and CINC-1 concentrations. The AAV vector itself did not contribute to inflammation or to lung injury. CONCLUSIONS: Pulmonary overexpression of EC-SOD protects the lung against endotoxin-induced ALI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-011-2309-y) contains supplementary material, which is available to authorized users.


Real -time PCR for early microbiological diagnosis: is it time?


docid: xvdlbbds

title: China steps up drive to vaccinate all domestic birds

text: Officials claim 8 billion birds inoculated so far.


Research in community-acquired pneumonia: the next steps


title: ARDS in a patient with homozygous beta-thalassemia due to yersiniosis

text: We report a case of Yersinia enterocolitica sepsis syndrome and the acute respiratory distress syndrome in a chronically transfused adolescent with beta-thalassemia. This manifestation of serious Y. enterocolitica infection has not previously been reported. Dyspnea, hypoxia, and fever were the principal features of the clinical presentation. The acute onset of respiratory symptoms occurred after appendectomy. Chest radiographs revealed frontal bilateral infiltrates and alveolar consolidation to three quadrants. Y. enterocolitica was identified from blood and intraoperative appendix cultures. Although there was no need for mechanical ventilation, a remarkable persistence of clinical and X-ray findings was noted. Therapy with high levels of oxygen, and intravenous amikacin and piperacillin/tazobactam led to a favorable outcome.


title: Acute polyneuropathy in critically ill patients

text: We studied five patients in the intensive care unit (ICU) with acute polyneuropathy. All had previously presented severe infectious processes, accompanied by diverse organ failure accompanied by the Adult Respiratory Distress Syndrome (ARDS) in all cases. Two patients died and the three survivors suffered severe motor deficiencies. Electromyographic studies revealed axonal damage which predominately affected motor neurons. Cerebrospinal fluid was normal in all the patients except one, who showed a moderate increase of lymphocytes. The common causes of polyneuropathy were excluded, but in all cases a nutritional disorder was detected, based on laboratory values of proteins, serum albumin and transferrin. We conclude that polyneuropathy is relatively frequent among critically ill patients and must be closely monitored because of diagnostic difficulties and the repercussions on the progress of these patients. In spite of uncertainties about its cause, it appears to be related to severe infectious processes, ARDS, and nutritional disorders.


title: Ventilator-associated pneumonia in adults: a narrative review

text: Ventilator-associated pneumonia (VAP) is one of the most frequent ICU-acquired infections. Reported incidences vary widely from 5 to 40% depending on the setting and diagnostic criteria. VAP is associated with prolonged duration of mechanical ventilation and ICU stay. The estimated attributable mortality of VAP is around 10%, with higher mortality rates in surgical ICU patients and in patients with mid-range severity scores at admission. Microbiological confirmation of infection is strongly encouraged. Which sampling method to use is still a matter of controversy. Emerging microbiological tools will likely modify our routine approach to diagnosing and treating VAP in the next future. Prevention of VAP is based on minimizing the exposure to mechanical ventilation and encouraging early liberation. Bundles that combine multiple prevention strategies may improve outcomes, but large randomized trials are needed to confirm this. Treatment should be limited to 7 days in the vast majority of the cases. Patients should be reassessed daily to confirm ongoing suspicion of disease, antibiotics should be narrowed as soon as antibiotic susceptibility results are available, and clinicians should consider stopping antibiotics if cultures are negative.


title: Critically ill obstetric patients in an American and an Indian public hospital: comparison of case-mix, organ dysfunction, intensive care requirements, and outcomes

text: OBJECTIVE: To compare case-mix, health care practices, and outcome in obstetric ICU admissions in inner-city teaching hospitals in economically developed and developing countries. DESIGN: Retrospective study. SETTING: Ben Taub General Hospital (BTGH), Houston, Texas, and King Edward Memorial Hospital (KEMH), Mumbai, India. PATIENTS: Women admitted during pregnancy or 6 weeks postpartum between 1992 and 2001. MEASUREMENTS AND RESULTS: Patients from BTGH (n=174) and KEMH (n=754) had comparable age, number of organs affected, incidence of medical disorders (30%), liver dysfunction, and thrombocytopenia. Fewer KEMH patients received prenatal care (27 vs 86%) and came to hospital within 24 h of onset of symptoms (60 vs 90%). They had higher APACHE II scores (median 16 vs 10), greater incidence of neurological (63 vs 36%), renal (50 vs 37%), and cardiovascular dysfunction (39 vs 29%). Severe malaria, viral hepatitis, cerebral venous thrombosis, and poisoning were common medical disorders. The BTGH group had higher incidence of respiratory dysfunction (59 vs 46%) and disseminated intravascular coagulation (40 vs 23%), placental anomalies, HELLP syndrome, chorioamnionitis, peripartum cardiomyopathy, puerperal sepsis, urinary infection, bacteremia, substance abuse, and asthma. More BTGH patients required mechanical ventilation and blood component therapy, whereas more KEMH patients needed dialysis. Of BTGH patients, 78.2% were delivered by cesarean section (vs 15.4%). Maternal (2.3 vs 25%) and fetal (13 vs 51%) mortality were lower in BTGH patients. CONCLUSIONS: There were marked differences in medical diseases, organ failure, and intensive care needs. Higher mortality in the Indian ICU may be due to difference in case mix, inadequate prenatal care, delay in reaching hospital, and greater severity of illness.


title: Public health: Life lessons

text: The 2009 pandemic arrived suddenly and lethally, exposing our plans to reality. Are we now better prepared?


title: Acute kidney injury in critically ill patients with 2009 influenza A (H1N1) viral pneumonia: an observational study

text: OBJECTIVE: To describe the incidence, risk factors, and impact on mortality of acute kidney injury (AKI) in patients with 2009 influenza A (H1N1) viral pneumonia requiring mechanical ventilation. DESIGN: Observational cohort study. PATIENTS AND METHODS: AKI was defined as risk, injury or failure, according to the RIFLE classification. Early and late AKI were defined as AKI occurring on intensive care unit (ICU) day 2 or before, or after ICU day 2, respectively. Demographic data and information on organ dysfunction were collected daily. RESULTS: Of 84 patients, AKI developed in 43 patients (51%). Twenty (24%) needed renal replacement therapy. Early and late AKI were found in 28 (33%) and 15 (18%) patients, respectively. Patients with AKI, as compared with patients without AKI, had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score and ICU mortality (72% versus 39%, p < 0.01) and presented on admission more marked cardiovascular, respiratory, and hematological dysfunction. Patients with early but not late AKI presented on admission higher APACHE II score and more marked organ dysfunction, as compared with patients without AKI. ICU mortality was higher in late versus early AKI (93% versus 61%, p < 0.001). On multivariate analysis, only APACHE II score and late but not early AKI [odds ratio (OR) 1.1 (95% confidence interval 1.0–1.1) and 15.1 (1.8–130.7), respectively] were associated with mortality. CONCLUSIONS: AKI is a frequent complication of 2009 influenza A (H1N1) viral pneumonia. AKI developing after 2 days in ICU appears to be associated with different risk factors than early AKI, and is related to a higher mortality rate.


What’s new in severe community-acquired pneumonia? Corticosteroids as adjunctive treatment to antibiotics


Is this critically ill patient immunocompromised?


Acute respiratory failure I. Morophology and pathophysiology


title: Inhaled nitric oxide for a severe respiratory syncytial virus infection in an infant with bronchopulmonary dysplasia

text: OBJECTIVE: To report the first case of ARDS in children treated with nitric oxide (NO) inhalation. METHODS: A 13-months infant presented with BPD and severe hypoxemia related to RSV infection and ARDS. Inhaled NO was delivered in the ventilatory circuit of a continuous flow ventilator (Babylog 8000, Dräger) in a concentration of 20–80 ppm for 7 days. NO and NO(2) were continuously monitored (Polyton Draeger). Respiratory mechanics were evaluated by using the method of passive inflation by the ventilator. RESULTS: NO inhalation improved oxygenation (tcSaO(2)) and reduced respiratory system resistance without affecting arterial pressure. NO(2) level remained below 5 ppm, and methaemoglobin level below 1%. The child survived without neurologic sequela. CONCLUSIONS: Two mechanisms to explain oxygenation improvement can be suggested:selective improvement in perfusion of ventilated regions and bronchodilation.


title: Massive rhabdomyolysis and multiple organ dysfunction syndrome caused by leptospirosis

text: We report a case of leptospiral infection in a 63-year-old man who acquired the infection while swimming in canals and streams in Hawaii. The patient's course was atypical in that he was anicteric and had no evidence of meningitis when he presented with fever, rapidly progressive and severe rhabdomyolysis, thrombocytopenia, acute renal failure, and respiratory distress syndrome. Although he recovered after a protracted illness, he required major life support, including mechanical ventilation and hemodialysis. Initial antimicrobial therapy was designed to cover major bacterial and atypical pathogens, including leptospires. An in-depth work-up for causes of this catastrophic illness confirmed acute leptospirosis. Although rare, leptospirosis is a potentially lethal infection classically associated with hepatitis, azotemia, and meningitis. Most patients experience self-limited illness, with fever, myalgias, and malaise followed by an immune-mediated aseptic meningitis. A small proportion develop shock and multiple organ dysfunction. Whereas myalgias are ubiquitous in leptospiral infection, and most patients show mildly elevated muscle enzymes, life-threatening rhabdomyolysis is rare. This atypical case is reported to urge clinicians to consider leptospirosis in the evaluation of a patient with cryptogenic sepsis who develops multiple organ dysfunction associated with rhabdomyolysis. Appropriate antimicrobial therapy, with penicillin or doxycycline, can be life-saving.


title: The role of blood microfilters in clinical practice

text: Blood filters have been available since the 1930s. In this review we evaluate the role of microaggregate filters (MF) in certain transfusion complications, namely non-haemolytic febrile transfusion reactions (NHFTR), pulmonary injury, thrombocytopenia, fibronectin depletion and histamine release. We review the latest generation of leucocyte depleting filters and discuss their role in preventing alloimmunisation, immunosuppression and CMV transmission. Finally, we provide a rationale for the role of blood microfiltration in the present day practice of intensive care medicine.


title: Evidence for lung repair and regeneration in humans: key stem cells and therapeutic functions of fibroblast growth factors

text: Regeneration carries the idea of regrowing partially or completely a missing organ. Repair, on the other hand, allows restoring the function of an existing but failing organ. The recognition that human lungs can both repair and regenerate is quite novel, the concept has not been widely used to treat patients. We present evidence that the human adult lung does repair and regenerate and introduce different ways to harness this power. Various types of lung stem cells are capable of proliferating and differentiating upon injury driving the repair/regeneration process. Injury models, primarily in mice, combined with lineage tracing studies, have allowed the identification of these important cells. Some of these cells, such as basal cells, broncho-alveolar stem cells, and alveolar type 2 cells, rely on fibroblast growth factor (FGF) signaling for their survival, proliferation and/or differentiation. While preclinical studies have shown the therapeutic benefits of FGFs, a recent clinical trial for acute respiratory distress syndrome (ARDS) using intravenous injection of FGF7 did not report the expected beneficial effects. We discuss the potential reasons for these negative results and propose the rationale for new approaches for future clinical trials, such as delivery of FGFs to the damaged lungs through efficient inhalation systems, which may be more promising than systemic exposure to FGFs. While this change in the administration route presents a challenge, the therapeutic promises displayed by FGFs are worth the effort.


title: Critically ill infants and children with influenza A (H1N1) in pediatric intensive care units in Argentina

text: OBJECTIVE: To determine the epidemiological features, course, and outcomes of critically ill pediatric patients with Influenza A (H1N1) virus. DESIGN: Prospective cohort of children in pediatric intensive care units (PICUs) due to Influenza A (H1N1) virus infection. SETTING: Seventeen medical-surgical PICUs in tertiary care hospital in Argentina. PATIENTS: All consecutive patients admitted to the PICUs with influenza A (H1N1) viral infection from 15 June to 31 July 2009. MEASUREMENTS AND MAIN RESULTS: Of 437 patients with acute lower respiratory infection in PICUs, 147 (34%) were diagnosed with influenza A (H1N1) related to critical illness. The median age of these patients was 10 months (IQR 3–59). Invasive mechanical ventilation was used in 117 (84%) on admission. The rate of acute respiratory distress syndrome (ARDS) was 80% (118 of 147 patients). Initial non-invasive ventilation failed in 19 of 22 attempts (86%). Mortality at 28 days was 39% (n = 57). Chronic complex conditions (CCCs), acute renal dysfunction (ARD) and ratio PaO(2)/FiO(2) at day 3 on MV were independently associated with a higher risk of mortality. The odds ratio (OR) for CCCs was 3.06, (CI 95% 1.36–6.84); OR for ARD, 3.38, (CI 95% 1.45–10.33); OR for PaO(2)/FiO(2), 4 (CI 95% 1.57–9.59). The administration of oseltamivir within 24 h after admission had a protective effect: OR 0.2 (CI 95% 0.07–0.54). CONCLUSIONS: In children with ARDS, H1N1 as an etiologic agent confers high mortality, and the presence of CCCs in such patients increases the risk of death.


Animal studies hint at staying power of SARS


Is it better to consent to an RCT or to care?: Μηδεν αγαν (“nothing in excess”)


title: Behandlungsstrategien des akut-auf-chronischen Leberversagens

text: Acute-on-chronic liver failure (ACLF) is a newly defined syndrome in patients with liver cirrhosis characterized by acute hepatic decompensation (jaundice, ascites, hepatic encephalopathy, bacterial infection and gastrointestinal bleeding), single or multiple organ failure and a high mortality (>15% within 28 days). The affected organ systems include not only the liver but also the circulation, lungs, kidneys, brain and/or coagulation. Pathophysiologically decisive is an uncontrolled inflammation that is induced by specific triggers and on the basis of previously (possibly not diagnosed) compensated as well as already decompensated liver cirrhosis leads to a severe systemic clinical syndrome, ACLF. The course during the first 72 h is decisive for the prognosis. In addition to treatment of the respective organ or system failure, the underlying triggers should be quickly identified and if necessary specifically treated. Often, however, these cannot (no longer) be determined with any certainty, in particular recent alcohol consumption as well as bacterial and viral infections play an important role. A specific treatment for the ACLF is (currently) not established. Some experimental approaches are currently being tested, including administration of granulocyte colony-stimulating factor (GCSF). Additionally, suitable patients should be presented to a liver transplantation center in a timely manner.


Singapore: Filling Biopolis


Swift response greets return of SARS in China


docid: rsfpwyen

title: An increased alveolar CD4 + CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality

text: PURPOSE: Cell therapy may become an option for lung injury treatment. However, no data are available on the alveolar presence and time course of CD4+ CD25 + Foxp3 + T-regulatory lymphocyte cells (Tregs) in acute respiratory distress syndrome (ARDS). Accordingly, we (1) measured the ratio of CD4 + CD25 + Foxp3 + Tregs to all (CD4+) lymphocytes in the bronchoalveolar lavage (BAL) of ARDS patients and of control subjects without lung disease and (2) assessed their impact on 30-day mortality. METHODS: In a prospective study, the ratios of CD4 + CD25 + Foxp3 + T-regulatory cells to all CD4+ cells were measured (FACS) within 24 h of the patients’ ICU referral in the BAL and in the blood of 47 patients with ARDS (32 males, 15 females; mean age 44 years ±13) as well as in 8 controls undergoing elective abdominal surgery (5 men, 3 women; mean age 49 years ±4). BAL concentrations of several cytokines were also measured in ARDS patients. RESULTS: Tregs were detected in the BAL of control subjects and ARDS patients. However, the mean ratio of Tregs to all CD4+ lymphocytes was threefold greater in ARDS non-survivors (16.5 %; p = 0.025) and almost twofold greater in ARDS survivors (9.0 %; p = 0.015) compared to controls (5.9 %). Multivariate Cox regression analysis revealed the ratio of CD4 + CD25 + Foxp3 + T-regulatory lymphocytes to all CD4+ lymphocytes in the BAL to be an important and independent prognostic factor for 30-day survival (HR 6.5; 95 % CI, 1.7–25; p = 0.006). CONCLUSION: An increased T-regulatory cell ratio in the admission BAL of patients with ARDS is an important and independent risk factor for 30-day mortality.


Oseltamivir carboxylate accumulation in a patient treated by haemodiafiltration and extracorporeal membrane oxygenation


Abstracts for ESICM-Barcelona 2014


title: Audit of intensive care: a 30 month experience using the Apache II severity of disease classification system

text: 608 patients admitted to a general Intensive Care Unit (ICU) over a 30 month period were analyzed according to the Apache II Severity of Disease Classification System on day one of admission. Hospital outcome details were available on 583 patients in the series. The mean Apache II scores for survivors (396) and non-survivors (187) were 13 (SD 7) and 24 (SD 9), and their Risk of Death were 16 (SD 16) and 47 (SD 27) respectively (p(0.001 for both). The majority of deaths (75%: 141/187) in our series came from those with chronic ill health (55%: 103/187), of whom 37% (38/103) were in endstage disease, and those with “old” trauma (18%: 34/187) often with incipient sepsis transferred from other hospitals after a mean delay of 9 days. Our higher than predicted mortality (mortality ratio 1.2) in comparison with centres in the United States of America (US) may be partly explained by the high proportion of our population from these unfavourable groups, by our use of the best Glasgow Coma Scale in the first 24 h following admission, and the major differences between our patient population and that of the US upon which the Apache II was based. The presence of these large unfavourable groups indicates a change in our admission policy is warranted.


Procalcitonin as a marker of the systemic inflammatory response to infection


title: Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury

text: OBJECTIVE: Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes. DESIGN: Prospective controlled study of ALI/ARDS. SETTING: Intensive care units and laboratory of a university hospital. PATIENTS AND PARTICIPANTS: Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients. INTERVENTIONS: Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-β1 levels were measured by ELISA. RESULTS: Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-β1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-β1 levels in the ARDS group compared to negative controls (−1.056 log(10)±0.1415 vs −1.505 log(10)±0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-β1 levels were associated with more ventilator-free and ICU-free days. CONCLUSIONS: Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-β1. Activated TGF-β1 may impact ARDS outcome independent of its effect on procollagen I activation. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-004-2503-2


title: Two cases of acute respiratory failure due to carcinomatous lymphangitis in HIV patients

text: In HIV-infected patients, acute respiratory failure is usually due to infectious pneumonia. In this report, we describe two cases of acute respiratory failure in HIV patients with clinical presentation suggesting infectious pneumonia. In both cases, the clinical condition deteriorated and death occurred after several days despite therapy. In both cases bronchial biopsies confirmedbronchogenic carcinoma responsible for carcinomatous lymphangitis.


ESICM 2012 MONDAY SESSIONS 15 October, 2012


title: Pediatric intestinal and multivisceral transplantation: a new challenge for the pediatric intensivist

text: INTRODUCTION: With increasing survival rates, intestinal transplantation (ITx) and multivisceral transplantation have reached the mainstream of medical care. Pediatric candidates for ITx often suffer from severe multisystem impairments that pose challenges to the medical team. These patients frequently require intensive care preoperatively and have unique intensive care needs postoperatively. METHODS: We reviewed the literature on intensive care of pediatric intestinal transplantation as well as our own experience. This review is not aimed only at pediatric intensivists from ITx centers; these patients frequently require ICU care at other institutions. RESULTS: Preoperative management focuses on optimization of organ function, minimizing ventilator-induced lung injury, preventing excessive edema yet maintaining adequate organ perfusion, preventing and controlling sepsis and bleeding from varices at enterocutaneous interfaces, and optimizing nutritional support. The goal is to extend life in stable condition to the point of transplantation. Postoperative care focuses on optimizing perfusion of the mesenteric circulation by maintaining intravascular volume, minimizing hypercoagulability, and providing adequate oxygen delivery. Careful monitoring of the stoma and its output and correction of electrolyte imbalances that may require renal replacement therapy is critical, as are monitoring for and aggressively treating infections, which often present with only subtle clinical clues. Signs of intestinal rejection may be non-specific, and early differentiation from other causes of intestinal dysfunction is important. Understanding of the expanding armamentarium of immunosuppressive agents and their side-effects is required. CONCLUSIONS: As outcomes of ITx improve, transplant teams accept patients with higher pre-operative morbidity and at higher risk for complications. Many ITx patients would benefit from earlier referral for transplant evaluation before severe liver disease, recurrent central venous catheter-related sepsis and venous thromboses develop.


Announcements


title: Hyperpolarization following activation of K(+) channels by excitatory postsynaptic potentials

text: We have postulated that an excitatory postsynaptic potential (e.p.s.p.) may open voltage-sensitive K(+) (‘M’) channels(1), in an appropriate depolarizing range, and that this could alter the e.p.s.p. waveform. Consequently, the fast e.p.s.p. in neurones of sympathetic ganglia, elicited by a nicotinic action of acetylcholine (ACh)(2), could be followed by a hyperpolarization, produced by the opening of M channels during the depolarizing e.p.s.p. and their subsequent slow closure (time constant∼150 ms)(1). This introduces the concept that transmitter-induced p.s.ps may trigger voltage-sensitive conductances other than those initiating action potentials, and that in the present case this could produce a true post-e.p.s.p. hyperpolarization. (Some hyperpolarizations other than inhibitory postsynaptic potentials (i.p.s.ps) have been reported to follow e.p.s.ps(3,4).) We show here that this is so.


docid: fuarcykw

title: Peduncular hallucinosis related to propranolol self-poisoning: efficacy of intravenous glucagon


title: There are two sides to biodefence

text: A mystery epidemic of pneumonia serves as a timely reminder that Mother Nature is the ultimate bioterrorist.


docid: nxfgqjzo

title: SARS, a challenge from the South

text: When an epidemic threatens the affluent countries, the response is fast and well-funded.


title: Shift expertise to where it matters

text: Tools and training for responding to diseases such as avian flu must relocate to countries where infections are most likely to emerge, says Jeremy Farrar.


title: We have been warned

text: The world is celebrating the news that the SARS outbreak now seems to be contained. But the epidemic has revealed gaps in our defences against emerging viral diseases and the ever-looming threat of a flu pandemic.


title: Non-invasive pressure support ventilation in severe community-acquired pneumonia

text: Objective: To explore three aspects of non-invasive pressure support ventilation (NIPSV) applied by face mask to patients with acute respiratory failure (ARF) due to severe community-acquired pneumonia (CAP): (1) the initial acute effects on respiratory rate, gas exchange and hemodynamics, (2) the clinical course and outcome during ICU and hospital stay, (3) the nursing workload as measured by the daily PRN 87 (Project Research in Nursing) score. Setting: Medical ICU, University Hospital. Design: Prospective, observational study. Patients: Patients without any prior history of chronic lung disease, consecutively admitted to the ICU to receive NIPSV for ARF due to severe CAP. Measurements and results (means ± SD): Twenty-four patients aged 49±17 years, admission APACHE II 13±5, were included. Admission PaO(2)/FIO(2), alveolar-arterial oxygen difference (DA-aO(2)) and PaCO(2) were 104±48, 447±120 and 40±10 mmHg, respectively. All patients were normotensive. During the initial NIPSV trial respiratory rate decreased from 34±8 to 28±10 breaths/min (p<0.001) and arterial oxygenation improved (PaO(2)/FIO(2) 104±48 vs 153±49, DA-aO(2) 447±120 vs 370±180 mmHg, p<0.001) while PaCO(2) remained unchanged. There were no hemodynamic effects. Subsequently, a total of 133 NIPSV trials were performed (median duration 55 min, range 30–540 min) over 1–7 days. No complication occurred during NIPSV. Sixteen patients were intubated (66%) 1.3±1 days after inclusion. Upon inclusion, the patients who were subsequently intubated were older (55±15 vs 37±12 years) and more severely hypoxemic (63±11 vs 80±15 mmHg, p<0.05) than those not requiring intubation. Eight patients died (33%), all in the intubated group. Median lengths of stay in the ICU and hospital were longer in intubated patients (ICU 16 days, range 3–64 vs 6 days, range 3–7, p<0.05; hospital 23 days, range 9–77 vs 9.5 days, range 4–42, p<0.05). Mean daily total PRN points were stable throughout the NIPSV period and were not different between the groups. Only 14% of PRN points resulted from respiratory therapy interventions. PRN score was higher during the first 24 h following intubation than during the first 24 h of NIPSV (278±55 vs 228±24 points, p<0.05). Conclusion: Despite initial improvement in arterial oxygenation with NIPSV in patients with ARF due to severe CAP, the intubation rate is high. However, the more favorable outcome and shorter ICU and hospital stays when intubation is avoided, as well as the short delay required to assess the success or failure of NIPSV warrants a trial of NIPSV in this setting. The nursing workload remains stable during NIPSV and does not result predominantly from respiratory therapy interventions.


Acute respiratory distress syndrome in kidney transplant recipients


ESICM 2010 MONDAY SESSIONS 11 October 2010


Mr. F. O. Barlow


title: Enter the dragon

text: Once a poor village, Shenzhen is now one of the wealthiest cities in China. David Cyranoski learns its plans for the future.


Acute respiratory distress syndrome and cutaneous eruption in an immunocompetent adult


Early oseltamivir therapy improves the outcome in critically ill patients with influenza: a propensity analysis


Fast vaccine offers hope in battle with Ebola


New insights in mechanical ventilation for pediatric patients


title: CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler’s murine encephalomyelitis virus-induced demyelinating disease

text: CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler’s murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease.


Exogenous surfactant therapy for acute respiratory distress in infancy


Pharmacokinetics of oseltamivir carboxylate in critically ill patients: each patient is unique


title: Mediators of multiple organ failure

text: Multiple Organ Failure (MOF) has largely been attributed to bacterial sepsis, though conclusive evidence of an essential role for bacteria and/or their endotoxins is still lacking. On the other hand, MOF and the clinical syndrome of sepsis may be aseptically induced in germfree animals. This paper reviews the evidence that excessive activation of endogenous humoral mediators and inflammatory cells may cause this highly lethal syndrome.


title: Extracorporeal membrane oxygenation for severe ARDS in pregnant and postpartum women during the 2009 H1N1 pandemic

text: PURPOSE: To describe the technical challenges, efficacy, complications and maternal and infant outcomes associated with extracorporeal membrane oxygenation (ECMO) for severe adult respiratory distress syndrome (ARDS) in pregnant or postpartum patients during the 2009 H1N1 pandemic. METHODS: Twelve critically ill pregnant and postpartum women were included in this retrospective observational study on the application of ECMO for the treatment of severe ARDS refractory to standard treatment. The study was conducted at seven tertiary hospitals in Australia and New Zealand. RESULTS: Of the 12 patients treated with ECMO, 7 (58%) were pregnant and 5 (42%) were postpartum. Their median (interquartile range [IQR]) age was 29 (26–33) years, 6 (50%) were obese. Two patients were initially treated with veno-arterial (VA) ECMO. All others received veno-venous (VV) ECMO with one or two drainage cannulae. ECMO circuit-related complications were rare, circuit change was needed in only two cases and there was no sudden circuit failure. On the other hand, bleeding was common, leading to relatively large volumes of packed red blood cell transfusion (median [IQR] volume transfused was 3,499 [1,451–4,874] ml) and was the main cause of death (three cases). Eight (66%) patients survived to discharge and seven were ambulant, with normal oxygen saturations. The survival rate of infants whose mothers received ECMO was 71% and surviving infants were discharged home with no sequelae. CONCLUSIONS: The use of ECMO for severe ARDS in pregnant and postpartum women was associated with a 66% survival rate. The most common cause of death was bleeding. Infants delivered of mothers who had received ECMO had a 71% survival rate and, like their mothers, had no permanent sequelae at hospital discharge. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-011-2138-z) contains supplementary material, which is available to authorized users.


China and Germany join forces over SARS


title: Emerging diseases go global

text: Novel human infections continue to appear all over the world, but the risk is higher in some regions than others. Identification of emerging-disease 'hotspots' will help target surveillance work.


ESPNIC 2011: 22nd Annual Congress of the European Society of Paediatric and Neonatal Intensive Care


title: Angiotensin-converting enzyme activity in serum and bronchoalveolar lavage fluid after damage to the alveolo-capillary barrier in the human lung

text: OBJECTIVE: Angiotensin-converting enzyme (ACE) is considered as a possible marker for endothelial cell damage in serum or bronchoalveolar lavage fluid. This hypothesis was tested during cardiac surgery and during the adult respiratory distress syndrome. DESIGN: We used patients with an expected different degree of endothelial cell damage. ACE levels in serum and bronchoalveolar lavage fluid were compared with indirect markers of alveolo-capillary barrier integrity. SETTING: Interdisciplinary team in a university hospital. METHODS: 13 Cardiac surgery patients received no glucocorticoids and 13 others received 2g methylprednisolone before extracorporeal circulation. Thirteen patients were used as controls and 15 patients had nonseptic adult respiratory distress syndrome. All underwent bronchoalveolar lavage for ACE determination. RESULTS: At different times during surgery serum angiotensin-converting enzyme levels were not significantly different between the two groups. In post-operative bronchoalveolar lavage fluid, angiotensin-converting enzyme levels were significantly higher in patients who received corticoids (27.8±1.7U/1, mean±SEM), compared to patients without corticoids (19.8±1.4U/1), control patients (18.2±1.3U/1) or patients with full blown non-septic adult respiratory distress syndrome (18.8±1.1U/1). There were no correlations between lavage angiotensin-converting enzyme and other parameters for alveolo-capillary membrane integrity in the lavage fluid such as the number of neutrophil cells, albumin or protein concentration, and between lavage angiotensin-converting enzyme and PaO(2)/FIO(2) ratio during lavage. CONCLUSION: Angiotensin-converting enzyme activity in serum or bronchoalveolar lavage fluid does not reflect damage of endothelial cells or damage of alveolocapillary integrity in acute pulmonary disease.


Correspondence


title: Engineering immune evasion

text: One obstacle to realizing the promise of viral vectors for vaccine delivery is pre-existing immunity to such vectors. An adroit application of structure-based design points to a way around that problem.


title: Surfactant replacement therapy in acute respiratory distress syndrome from viral pneumonia

text: A modified natural surfactant was administered to a patient with life-threatening adult respiratory distress sydrome caused by viral pneumonia. Subsequently, there was a marked improvement in gas exchange. In order to assess the mechanism for improved oxygenation, computed tomography of the lungs was done. Quantitative analysis of the scans taken before and after surfactant administration indicates that improvement in gas exchange was largely due to the expansion of underinflated and collapsed lung areas. Although this is a single case report, it provides insight into the possible beneficial effect of instilled surfactant in severe respiratory distress from viral pneumonia.


Kaposi’s sarcoma: a reversible cause of ARDS in HIV-infected patient


title: Acute respiratory distress syndrome: is it underrecognized in the pediatric intensive care unit?

text: OBJECTIVE: To describe the incidence of acute respiratory distress syndrome (ARDS) in mechanically ventilated children and to study whether ARDS is underrecognized in this patient population. DESIGN AND SETTING: Retrospective observational study in a single-center bed pediatric intensive care unit serving two Dutch provinces. PATIENTS: 533 mechanically ventilated children aged 0–16 years, all of whom met the North-American European Consensus Conference criteria for ARDS. MEASUREMENTS AND RESULTS: Chest radiographs were screened for the novel presence of bilateral infiltrates, in patients with bilateral infiltrates the PaO(2)/FIO(2) ratio was calculated on two separate consecutive measurements. If below 200, the patient was classified as having ARDS. Left ventricular dysfunction was ruled out by echocardiography. The incidence was calculated by obtaining the number of children aged 0–16 years in our region. For each patient it was noted whether the patient was currently considered to have ARDS. Forty-one patients (7.7%) met the criteria for ARDS, with an incidence of 2.2 per 100,000 per year. The mortality rate was 20.4%. Thirty patients (73.1%) had primary ARDS, mainly from viral lower respiratory tract disease. Only ten patients (24.4%) currently had ARDS. CONCLUSIONS: The incidence of pediatric ARDS is low compared to that of adult ARDS, and further underestimated as most patients were diagnosed by their underlying diseases.


title: De-escalation therapy rates are significantly higher by bronchoalveolar lavage than by tracheal aspirate

text: OBJECTIVE: To assess outcomes with de-escalation therapy in ventilator-associated pneumonia (VAP). DESIGN: Prospective observational study. SETTING: Multidisciplinary intensive care unit. PATIENTS AND PARTICIPANTS: VAP was diagnosed by positive quantitative cultures of both tracheal aspirate and bronchoalveolar lavage (BAL) and treated appropriately for all significant isolates of tracheal aspirate and BAL in 143 patients who were assigned to de-escalation therapy by BAL or tracheal aspirate. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Antibiotic therapy was de-escalated in 58 patients (40.5%), who had decreased mortality at day 15 (5.1% vs. 31.7%) and day 28 (12% vs. 43.5%) and shorter intensive care unit (17.2 ± 1.2 vs. 22.7 ± 6.3 days) and hospital (23.7 ± 2.8 vs. 29.8 ± 11.1 days) stay (p < 0.05). Of the 81 patients assigned to tracheal aspirate, the 17 (21%) who achieved de-escalation of therapy had reduced 15-day mortality (5.8% vs. 34.3%), reduced 28-day mortality (11.6% vs. 45.3%), and shorter intensive care unit (17.2 ± 1.6 vs. 22.4 ± 6.4 days) and hospital (23.1 ± 4.4 vs. 29.9 ± 11.1 days) stay (p < 0.05). Of the 62 patients assigned to BAL, the 41 (66.1%) who achieved de-escalation of therapy had decreased 15-day mortality (4.8% vs. 23.8%), decreased 28-day mortality (12.1% vs. 38%), and shorter intensive care unit (17.2 ± 1.1 vs. 23.2 ± 6 days) and hospital (23.8 ± 2.4 vs. 29.8 ± 11.4 days) stay (p < 0.05). CONCLUSIONS: For patients with VAP who have had appropriate treatment and shown a favorable clinical response, mortality and duration of stay can be further improved by de-escalation therapy.


title: Comparison of clinical outcomes of influenza A and B at the 2017–2018 influenza season: a cohort study

text: Influenza has significant morbidity and mortality. Some experts consider infection with influenza B as milder than that with influenza A. The objective of this study is to evaluate the outcomes of hospitalized patients with laboratory-confirmed influenza A or B in 2017–2018 influenza season. All hospitalized patients between October 2017 and April 2018 with laboratory-confirmed influenza A and B were included. The primary composite outcomes were pneumonia/myocarditis/encephalitis, mechanical ventilation, ICU admission, and 30-day mortality. Secondary outcomes were 30-/90-day mortality, length of hospital stay, and readmission rates. The study included 201 influenza A and 325 influenza B. For the primary composite outcome, no significant difference was demonstrated between influenza A and B. Rates of mortality were similar at 30 and 90 days. Influenza A had higher pneumonia rates and mechanical ventilation. On multivariate analysis, higher Charlson’s score, hypoalbuminemia, and vasopressor use were associated with 30-day mortality, while infection with either influenza A or B was not. Influenza A was associated with higher pneumonia and mechanical ventilation rates. However, influenza B resulted with similar 30-day mortality rate as influenza A.


Year in review in Intensive Care Medicine, 2008: III. Paediatrics, Ethics, outcome research and critical care organization, sedation, pharmacology and miscellanea


title: A canine distemper virus epidemic in Serengeti lions (Panthera leo)

text: CANINE distemper virus (CDV) is thought to have caused several fatal epidemics in canids within the Serengeti–Mara ecosystem of East Africa, affecting silver-backed jackals (Canis mesomelas) and bat-eared foxes (Otocyon megalotis) in 1978 (ref. 1), and African wild dogs (Lycaon pictus) in 1991 (refs 2, 3). The large, closely monitored Serengeti lion population(4,5) was not affected in these epidemics. However, an epidemic caused by a morbillivirus closely related to CDV emerged abruptly in the lion population of the Serengeti National Park, Tanzania, in early 1994, resulting in fatal neurological disease characterized by grand mal seizures and myoclonus; the lions that died had encephalitis and pneumonia. Here we report the identification of CDV from these lions, and the close phylogenetic relationship between CDV isolates from lions and domestic dogs. By August 1994, 85% of the Serengeti lion population had anti-CDV antibodies, and the epidemic spread north to lions in the Maasai Mara National reserve, Kenya, and uncounted hyaenas, bat-eared foxes, and leopards were also affected.


Parechovirus infection preceding Guillain–Barré syndrome


Skin rash in a patient with A(H1N1) infection


title: Impact of antifungal treatment on Candida–Pseudomonas interaction: a preliminary retrospective case–control study

text: OBJECTIVE: A pathogenic interaction between Candida albicans and Pseudomonas aeruginosa has recently been demonstrated. In addition, experimental and clinical studies identified Candida spp. tracheobronchial colonization as a risk factor for P. aeruginosa pneumonia. The aim of this study was to determine the impact of antifungal treatment on ventilator-associated pneumonia (VAP) or tracheobronchial colonization due to P. aeruginosa. DESIGN AND SETTING: Retrospective observational case–control study conducted in a 30-bed ICU during a 1-year period. PATIENTS AND METHODS: One hundred and two patients intubated and ventilated for longer than 48 h with tracheobronchial colonization by Candida spp. Routine screening for Candida spp. and P. aeruginosa was performed at ICU admission and weekly. Antifungal treatment was based on medical staff decisions. Patients with P. aeruginosa VAP or tracheobronchial colonization were matched (1:2) with patients without P. aeruginosa VAP or tracheobronchial colonization. In case and control patients, risk factors for P. aeruginosa VAP or tracheobronchial colonization were determined using univariate and multivariate analyses. RESULTS: Thirty-six patients (35%) received antifungal treatment. Nineteen patients (18%) developed a P. aeruginosa VAP or tracheobronchial colonization, and all were successfully matched. Antifungal treatment [31% vs 60%; p = 0.037, OR (95% CI) = 0.67 (0.45–0.90)], and duration of antifungal treatment (7 ± 11 vs 14 ± 14 days; p = 0.045, in case and control patients respectively) were significantly associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization. Antifungal treatment was the only variable independently associated with P. aeruginosa VAP or tracheobronchial colonization (OR = 0.68, 95% CI = 0.49–0.90, p = 0.046). CONCLUSION: In patients with Candida spp. tracheobronchial colonization, antifungal treatment may be associated with reduced risk for P. aeruginosa VAP or tracheobronchial colonization. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-006-0422-0 and is accessible for authorized users.


title: Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality

text: PURPOSE: To provide a practical overview of the management of the potential organ donor in the intensive care unit. METHODS: Seven areas of donor management were considered for this review: hemodynamic management; fluids and electrolytes; respiratory management; endocrine management; temperature management; anaemia and coagulation; infection management. For each subchapter, a narrative review was conducted. RESULTS AND CONCLUSIONS: Most elements in the current recommendations and guidelines are based on pathophysiological reasoning, epidemiological observations, or extrapolations from general ICU management strategies, and not on evidence from randomized controlled trials. The cardiorespiratory management of brain-dead donors is very similar to the management of critically ill patients, and the same applies to the management of anaemia and coagulation. Central diabetes insipidus is of particular concern, and should be diagnosed based on clinical criteria. Depending on the degree of vasopressor dependency, it can be treated with intermittent desmopressin or continuous vasopressin, intravenously. Temperature management of the donor is an area of uncertainty, but it appears reasonable to strive for a core temperature of > 35 °C. The indications and controversies regarding endocrine therapies, in particular thyroid hormone replacement therapy, and corticosteroid therapy, are discussed. The potential donor should be assessed clinically for infections, and screening tests for specific infections are an essential part of donor management. Although the rate of infection transmission from donor to receptor is low, certain infections are still a formal contraindication to organ donation. However, new antiviral drugs and strategies now allow organ donation from certain infected donors to be done safely.


Hypertriglyceridaemia associated with propofol sedation in critically ill patients


title: Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: the ECMOnet score

text: PURPOSE: The decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation. METHODS: This was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines. RESULTS: The survival rate in patients treated with ECMO was 68 %. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (OR = 1.52, 95 % CI 1.12–2.07, p = 0.008); bilirubin (OR = 2.32, 95 % CI 1.52–3.52, p < 0.001), creatinine (OR = 7.38, 95 % CI 1.43–38.11, p = 0.02) and hematocrit values (OR = 0.82, 95 % CI 0.72–0.94, p = 0.006); and mean arterial pressure (OR = 0.92, 95 % CI 0.88–0.97, p < 0.001). The ECMOnet score was developed based on these variables, with a score of 4.5 being the most appropriate cutoff for mortality risk prediction. The high accuracy of the ECMOnet score was further confirmed by ROC analysis (c = 0.857, 95 % CI 0.754–0.959, p < 0.001) and by an independent external validation analysis (c = 0.694, 95 % CI 0.562–0.826, p = 0.004). CONCLUSIONS: Mortality risk for patients receiving VV ECMO is correlated to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet score is a tool for the evaluation of the appropriateness and timing of VV ECMO in acute lung failure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-012-2747-1) contains supplementary material, which is available to authorized users.


Guidelines for a training programme in intensive care medicine


Anti-inflammatory therapies: application of molecular biology techniques in intensive care medicine


title: Emerging disease: Looking for trouble

text: How do you persuade philanthropists to pay $1 million for every pathogenic human virus you discover? Anjali Nayar talks to 'virus hunter' Nathan Wolfe in Cameroon to find out.


title: Phillyrin Relieves Lipopolysaccharide-Induced AKI by Protecting Against Glycocalyx Damage and Inhibiting Inflammatory Responses

text: Damage to the integrity of heparin sulfate (HS) in the endothelial glycocalyx is an important factor of glomerular filtration barrier dysfunction, which is the basic pathological feature of acute kidney injury (AKI). AKI is a common clinical critical illness with few drugs options offering effective treatment. Phillyrin (Phil), the main pharmacological component of Forsythia suspensa, possesses a wide range of pharmacological activities. However, the effects of Phil on lipopolysaccharide (LPS)-induced AKI have yet to be reported. The aim of the present study is to analyze the effects of Phil on HS damage and inflammatory signaling pathways in LPS-induced AKI. Results revealed that Phil reduces pathological changes and improves renal function in LPS-induced AKI. Further analysis indicated that Phil effectively protects against glycocalyx HS degradation in LPS-stimulated EA.hy926 cells in vitro and LPS-induced AKI mice in vivo. The protective effect of Phil on HS damage may be associated with the isolate’s ability to suppress the production of reactive oxygen species, and decrease expression levels of cathepsin L and heparanase in vitro and in vivo. In addition, ELISA and Western blot results revealed that Phil inhibits the activation of the NF-κB and MAPK signaling pathways and decreases the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in LPS-induced ARDS mice. In general, protection against endothelial glycocalyx HS damage and inhibition of inflammatory responses by Phil may be used as treatment targets for LPS-induced AKI.