Unfortunately, many COPD patients continue to exacerbate despite good adherence to GOLD Class D recommended therapy. Acute exacerbations lead to an increase in symptoms, decline in lung function and ...increased mortality rate. The purpose of this review is to do a literature search for any prophylactic anti-microbial treatment trials in GOLD class D patients who 'failed' recommended therapy and discuss the role of COPD phenotypes, lung and gut microbiota and co-morbidities in developing a tailored approach to anti-microbial therapies for high frequency exacerbators.
There is a paucity of large, well-conducted studies in the published literature to date. Factors such as single-centre, study design, lack of well-defined controls, insufficient patient numbers enrolled and short follow-up periods were significant limiting factors in numerous studies. One placebo-controlled study involving more than 1000 patients, who had 2 or more moderate exacerbations in the previous year, demonstrated a non-significant reduction in exacerbations of 19% with 5 day course of moxifloxacillin repeated at 8 week intervals. In Pseudomonas aeruginosa (Pa) colonised COPD patients, inhaled antimicrobial therapy using tobramycin, colistin and gentamicin resulted in significant reductions in exacerbation frequency. Viruses were found to frequently cause acute exacerbations in COPD (AECOPD), either as the primary infecting agent or as a co-factor. However, other, than the influenza vaccination, there were no trials of anti-viral therapies that resulted in a positive effect on reducing AECOPD. Identifying clinical phenotypes and co-existing conditions that impact on exacerbation frequency and severity is essential to provide individualised treatment with targeted therapies. The role of the lung and gut microbiome is increasingly recognised and identification of pathogenic bacteria will likely play an important role in personalised antimicrobial therapies.
Antimicrobial therapeutic options in patients who continue to exacerbate despite adherence to guidelines-directed therapy are limited. Phenotyping patients, identification of co-existing conditions and assessment of the microbiome is key to individualising antimicrobial therapy. Given the impact of viruses on AECOPD, anti-viral therapeutic agents and targeted anti-viral vaccinations should be the focus of future research studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Central gray matter damage, the hallmark of term acute perinatal hypoxia-ischemia, frequently leads to severe cerebral palsy and sometimes death. The precision with which these outcomes can be ...determined from neonatal imaging has not been fully explored. We evaluated the accuracy of early brain MRI for predicting death, the presence and severity of motor impairment, and ability to walk at 2 years in term infants with hypoxic-ischemic encephalopathy (HIE) and basal ganglia-thalamic (BGT) lesions.
From 1993 to 2007, 175 term infants with evidence of perinatal asphyxia, HIE, and BGT injury seen on early MRI scans were studied. BGT, white matter, posterior limb of the internal capsule (PLIC), and cortex and brainstem abnormality were classified by severity. Motor impairment was staged using the Gross Motor Function Classification System.
The severity of BGT lesions was strongly associated with the severity of motor impairment (Spearman rank correlation 0.77; p < 0.001). The association between white matter, cortical, and brainstem injury and motor impairment was less strong and only BGT injury correlated significantly in a logistic regression model. The predictive accuracy of severe BGT lesions for severe motor impairment was 0.89 (95% confidence interval 0.83-0.96). Abnormal PLIC signal intensity predicted the inability to walk independently by 2 years (sensitivity 0.92, specificity 0.77, positive predictive value 0.88, negative predictive value 0.85). Brainstem injury was the only factor with an independent association with death.
We have shown that in term newborns with HIE and BGT injury, early MRI can be used to predict death and specific motor outcomes.
Campylobacter jejuni, from the delta-epsilon group of proteobacteria,
is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties
it shares with the related gastric pathogen ...Helicobacter pylori. It
is the leading cause of bacterial food-borne diarrhoeal disease throughout
the world. In addition, infection with C. jejuni is
the most frequent antecedent to a form of neuromuscular paralysis known as
Guillain-Barré syndrome. Here we report the genome
sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome
of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins
and 54 stable RNA species. The genome is unusual in that there are virtually
no insertion sequences or phage-associated sequences and very few repeat sequences.
One of the most striking findings in the genome was the presence of hypervariable
sequences. These short homopolymeric runs of nucleotides were commonly found
in genes encoding the biosynthesis or modification of surface structures,
or in closely linked genes of unknown function. The apparently high rate of
variation of these homopolymeric tracts may be important in the survival strategy
of C. jejuni.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The Gene Ontology resource (GO; http://geneontology.org) provides structured, computable knowledge regarding the functions of genes and gene products. Founded in 1998, GO has become widely ...adopted in the life sciences, and its contents are under continual improvement, both in quantity and in quality. Here, we report the major developments of the GO resource during the past two years. Each monthly release of the GO resource is now packaged and given a unique identifier (DOI), enabling GO-based analyses on a specific release to be reproduced in the future. The molecular function ontology has been refactored to better represent the overall activities of gene products, with a focus on transcription regulator activities. Quality assurance efforts have been ramped up to address potentially out-of-date or inaccurate annotations. New evidence codes for high-throughput experiments now enable users to filter out annotations obtained from these sources. GO-CAM, a new framework for representing gene function that is more expressive than standard GO annotations, has been released, and users can now explore the growing repository of these models. We also provide the ‘GO ribbon’ widget for visualizing GO annotations to a gene; the widget can be easily embedded in any web page.
A uniform description of brain MR imaging findings in infants with severe congenital heart disease to assess risk factors, predict outcome, and compare centers is lacking. Our objective was to ...uniformly describe the spectrum of perioperative brain MR imaging findings in infants with congenital heart disease.
Prospective observational studies were performed at 3 European centers between 2009 and 2019. Brain MR imaging was performed preoperatively and/or postoperatively in infants with transposition of the great arteries, single-ventricle physiology, or left ventricular outflow tract obstruction undergoing cardiac surgery within the first 6 weeks of life. Brain injury was assessed on T1, T2, DWI, SWI, and MRV. A subsample of images was assessed jointly to reach a consensus.
A total of 348 MR imaging scans (180 preoperatively, 168 postoperatively, 146 pre- and postoperatively) were obtained in 202 infants. Preoperative, new postoperative, and cumulative postoperative white matter injury was identified in 25%, 30%, and 36%; arterial ischemic stroke, in 6%, 10%, and 14%; hypoxic-ischemic watershed injury in 2%, 1%, and 1%; intraparenchymal cerebral hemorrhage, in 0%, 4%, and 5%; cerebellar hemorrhage, in 6%, 2%, and 6%; intraventricular hemorrhage, in 14%, 6%, and 13%; subdural hemorrhage, in 29%, 17%, and 29%; and cerebral sinovenous thrombosis, in 0%, 10%, and 10%, respectively.
A broad spectrum of perioperative brain MR imaging findings was found in infants with severe congenital heart disease. We propose an MR imaging protocol including T1-, T2-, diffusion-, and susceptibility-weighted imaging, and MRV to identify ischemic, hemorrhagic, and thrombotic lesions observed in this patient group.
Cough peak flow (CPF) is a useful clinical measurement to assess neuromuscular activity and effective coordination, yet it is rarely used in clinical practice outside of the management of patients ...with neuromuscular disorders. A CPF of above 160 L/min is required for an effective cough and less than 270 L/min is associated with increased secretion retention and risk of infection. Reduced CPF can be due to a number of mechanisms including reduced respiratory muscle strength, lack of co-ordination of glottic closure and opening, airway obstruction and, age and activity related changes. CPF has been shown to be correlated with other measures of pulmonary function in neuromuscular disorders and in predicting extubation failure. Patients with Parkinson's disease have a reduced CPF even at early stages and dedicated expiratory muscle strength training (EMST) has been shown to be beneficial. Sequential studies in patient with stroke-associated dysphagia reported CPF was correlated with risk of respiratory infection and results of formal swallow assessments.
Age-related changes in expiratory muscle strength and lung physiology contribute to increased risk of aspiration and pneumonia. EMST may have a role in healthy adults to improve muscle strength and effective cough, potentially reducing risk of respiratory tract infections even in the absence of disease.
CPF has potential to be extremely useful in clinical practice in a wide spectrum of diseases. In particular, studies in patients with frequent exacerbations of COPD and recurrent pneumonia are currently lacking and would be of benefit to explore the relationship between ineffective cough and recurrent infection.
•Cough peak flow (CPF) is an under-utilised tool to measure the maximum expiratory flow.•CPF has been mainly studied in patients with neuromuscular diseases (NMDs) and to predict the success of extubation.•The utility of CPF in other conditions merits further validated studies.
Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis ...that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR imaging were consistently linearly related to specific local changes in white matter microstructure. We studied 33 children, born at a median (range) gestational age of 28+5 (24+4–32+1) weeks. The children were recruited as infants from the Neonatal Intensive Care Unit at Queen Charlotte's and Hammersmith Hospital in the early neonatal period and imaged at a median corrected age of 25.5 (24–27) months. The children underwent diffusion tensor imaging to measure fractional anisotropy (FA) as a measure of tissue microstructure, and neurodevelopmental assessment using the Griffiths Mental Development Scales giving an overall developmental quotient (DQ) and sub-quotients scores for motor, personal–social, hearing–language, eye–hand coordination and performance scales at 2 years corrected age. Tract-based spatial statistics with linear regression analysis of voxel-wise cross-subject statistics were used to assess the relationship between FA and DQ/sub-quotient scores and results confirmed by reduced major axis regression of regions with significant correlations. We found that DQ was linearly related to FA values in parts of the corpus callosum; performance sub-scores to FA values in the corpus callosum and right cingulum; and eye–hand coordination sub-scores to FA values in the cingulum, fornix, anterior commissure, corpus callosum and right uncinate fasciculus. This study shows that specific neurodevelopmental impairments in infants born preterm are precisely related to microstructural abnormalities in particular regions of cerebral white matter which are consistent between individuals. FA may aid prognostication and provide a biomarker for therapeutic or mechanistic studies of preterm brain injury.
Diffuse white matter injury is common in preterm infants and is a candidate substrate for later cognitive impairment. This injury pattern is associated with morphological changes in deep grey nuclei, ...the localization of which is uncertain. We test the hypotheses that diffuse white matter injury is associated with discrete focal tissue loss, and that this image phenotype is associated with impairment at 2
years.
We acquired magnetic resonance images from 80 preterm infants at term equivalent (mean gestational age 29
+
6
weeks) and 20 control infants (mean GA 39
+
2
weeks). Diffuse white matter injury was defined by abnormal apparent diffusion coefficient values in one or more white matter region (frontal, central or posterior white matter at the level of the centrum semiovale), and morphological difference between groups was calculated from 3D images using deformation based morphometry. Neurodevelopmental assessments were obtained from preterm infants at a mean chronological age of 27.5
months, and from controls at a mean age of 31.1
months.
We identified a common image phenotype in 66 of 80 preterm infants at term equivalent comprising: diffuse white matter injury; and tissue volume reduction in the dorsomedial nucleus of the thalamus, the globus pallidus, periventricular white matter, the corona radiata and within the central region of the centrum semiovale (
t
=
4.42
p
<
0.001 false discovery rate corrected). The abnormal image phenotype is associated with reduced median developmental quotient (DQ) at 2
years (DQ
=
92) compared with control infants (DQ
=
112),
p
<
0.001.
These findings indicate that specific neural systems are susceptible to maldevelopment after preterm birth, and suggest that neonatal image phenotype may serve as a useful biomarker for studying mechanisms of injury and the effect of putative therapeutic interventions.
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