Annotation of Three Actinobacteriophages: TukTuk, Shamu, and Megatron06

We annotated three newly discovered bacteriophages. TukTuk and Shamu were isolated on the host Microbacterium folorium and Megatron06 on Mycobacterium smegmatis. Based on based on gene-content similarity (GCS) of 35% or higher to sequenced bacteriophages present in the Actinobacteriophage database, phagesDB, TukTuk was assigned to cluster EB, Shamu to cluster EA, and Megatron06 to Cluster H1. Here we report a summary of our annotation findings along with one in-depth analysis of an aspect of our annotation for each phage

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy

Objective: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. Patients and methods: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. Results: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). Conclusions: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further

Diet and body constitution in relation to subgroups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators

BACKGROUND: The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases. METHOD: A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmö Diet and Cancer study (Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance. RESULTS: A large hip circumference and high body mass index were associated with high grade tumours (P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation (P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation (P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D(1 )overexpression (P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution. CONCLUSION: Low energy and low total fat (polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D(1 )and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results

Acute hypoxemic respiratory failure in immunocompromised patients : the Efraim multinational prospective cohort study

In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86-0.99), day-1 SOFA (1.09/point, 1.06-1.13), day-1 PaO2/FiO(2) (1.47, 1.05-2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42-3.14), invasive pulmonary aspergillosis (1.85, 1.21-2.85), and undetermined cause (1.46, 1.09-1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59-1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09-1.27), direct admission to the ICU (0.69, 0.54-0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08-1.16), PaO2/FiO(2) <100 (1.60, 1.03-2.48), and undetermined ARF etiology (1.43, 1.04-1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09-4.91), first-line IMV (2.55, 1.94-3.29), NIV failure (3.65, 2.05-6.53), standard oxygen failure (4.16, 2.91-5.93), and HFNC failure (5.54, 3.27-9.38). HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.Peer reviewe

Plasma exchange in the intensive care unit: a narrative review

International audienc

Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study

Background: In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV). Methods: To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers). Results: A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86â\u80\u930.99), day-1 SOFA (1.09/point, 1.06â\u80\u931.13), day-1 PaO2/FiO2(1.47, 1.05â\u80\u932.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42â\u80\u933.14), invasive pulmonary aspergillosis (1.85, 1.21â\u80\u932.85), and undetermined cause (1.46, 1.09â\u80\u931.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59â\u80\u931.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09â\u80\u931.27), direct admission to the ICU (0.69, 0.54â\u80\u930.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08â\u80\u931.16), PaO2/FiO2 < 100 (1.60, 1.03â\u80\u932.48), and undetermined ARF etiology (1.43, 1.04â\u80\u931.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09â\u80\u934.91), first-line IMV (2.55, 1.94â\u80\u933.29), NIV failure (3.65, 2.05â\u80\u936.53), standard oxygen failure (4.16, 2.91â\u80\u935.93), and HFNC failure (5.54, 3.27â\u80\u939.38). Conclusion: HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF