Background: The optimal choice of chest tube size for the treatment of pleural infection is unknown, with only small cohort studies reported
describing the efficacy and adverse events of different ...tube sizes.
Methods: A total of 405 patients with pleural infection were prospectively enrolled into a multicenter study investigating the utility
of fibrinolytic therapy. The combined frequency of death and surgery, and secondary outcomes (hospital stay, change in chest
radiograph, and lung function at 3 months) were compared in patients receiving chest tubes of differing size (Ï 2 , t test, and logistic regression analyses as appropriate). Pain was studied in detail in 128 patients.
Results: There was no significant difference in the frequency with which patients either died or required thoracic surgery in patients
receiving chest tubes of varying sizes ( < 10F, number dying or needing surgery 21/58 36%; size 10-14F, 75/208 36%; size
15-20F, 28/70 40%; size > 20F, 30/69 44%; Ï 2 trend, 1 degrees of freedom df = 1.21, P = .27), nor any difference in any secondary outcome. Pain scores were substantially higher in patients receiving (mainly
blunt dissection inserted) larger tubes ( < 10F, median pain score 6 range 4-7; 10-14F, 5 4-6; 15-20F, 6 5-7; > 20F,
6 6-8; Ï 2 , 3 df = 10.80, P = .013, Kruskal-Wallis; Ï 2 trend, 1 df = 6.3, P = .014).
Conclusions: Smaller, guide-wire-inserted chest tubes cause substantially less pain than blunt-dissection-inserted larger tubes, without
any impairment in clinical outcome in the treatment of pleural infection. These results suggest that smaller size tubes may
be the initial treatment of choice for pleural infection, and randomized studies are now required.
Trial registration: MIST1 trial ISRCTN number: 39138989.
Pleural infection is common, and has a >30% major morbidity and mortality-particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural ...fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform.
To determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce.
62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for 'false-positive' results.
The addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference -2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative.
Blood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.
Inexpensive genotyping methods are essential for genetic studies requiring large sample sizes. In human studies, array-based microarrays and high-density haplotype reference panels allow efficient ...genotype imputation for this purpose. However, these resources are typically unavailable in non-human settings. Here we describe a method (STITCH) for imputation based only on sequencing read data, without requiring additional reference panels or array data. We demonstrate its applicability even in settings of extremely low sequencing coverage, by accurately imputing 5.7 million SNPs at a mean r(2) value of 0.98 in 2,073 outbred laboratory mice (0.15× sequencing coverage). In a sample of 11,670 Han Chinese (1.7× coverage), we achieve accuracy similar to that of alternative approaches that require a reference panel, demonstrating that our approach can work for genetically diverse populations. Our method enables straightforward progression from low-coverage sequence to imputed genotypes, overcoming barriers that at present restrict the application of genome-wide association study technology outside humans.
Antibiotic choices for pleural infection are uncertain as its bacteriology is poorly described.
Pleural fluid from 434 pleural infections underwent standard culture and a screen for bacteria by ...amplification and sequencing of bacterial 16S ribosomal RNA gene.
Approximately 50% of community-acquired infections were streptococcal, and 20% included anaerobic bacteria. Approximately 60% of hospital-acquired infections included bacteria frequently resistant to antibiotics (methicillin-resistant Staphylococcus aureus, 25%; Enterobacteriaceae, 18%; Pseudomonas spp., 5%, enterococci, 12%). Mortality was increased in hospital-acquired infection (hospital, 17/36 47%; community, 53/304 17%; relative risk, 4.24; 95% confidence interval, 2.07-8.69; p < 0.00001; chi(2), 1 df = 17.47) and in gram-negative (10/22 45%), S. aureus (15/34 44%), or mixed aerobic infections (13/28 46%), compared with streptococcal infection (23/137 17%) and infection including anaerobic bacteria (10/49 20%; p < 0.00001, chi(2), 4 df = 23.35).
Pleural infection differs bacteriologically from pneumonia and requires different treatment. Antibiotics for community-acquired infection should treat aerobic and anaerobic bacteria. Hospital-acquired, gram-negative S. aureus and mixed aerobic infections have a high mortality rate.
During meiotic recombination, homologue-templated repair of programmed DNA double-strand breaks (DSBs) produces relatively few crossovers and many difficult-to-detect non-crossovers. By intercrossing ...two diverged mouse subspecies over five generations and deep-sequencing 119 offspring, we detect thousands of crossover and non-crossover events genome-wide with unprecedented power and spatial resolution. We find that both crossovers and non-crossovers are strongly depleted at DSB hotspots where the DSB-positioning protein PRDM9 fails to bind to the unbroken homologous chromosome, revealing that PRDM9 also functions to promote homologue-templated repair. Our results show that complex non-crossovers are much rarer in mice than humans, consistent with complex events arising from accumulated non-programmed DNA damage. Unexpectedly, we also find that GC-biased gene conversion is restricted to non-crossover tracts containing only one mismatch. These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9-related hybrid infertility.
The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the ...respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0-10. Substantial agreement (range 7.5-10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post COVID-19 illness, for a target population of active individuals, including military personnel and athletes.
Readily accessible tartramide ligands have been demonstrated to promote copper‐catalysed N‐arylation under mild conditions. In addition, the coupling protocol employs cheap and readily available ...pre‐catalyst, ligand, and base (NaOH), and overcomes many current limitations often associated with Ullmann coupling: it can be run with low catalyst loadings, does not require the use of excess amine, operates at room temperature, is fully homogeneous, and displays improved tolerance to air and moisture. Detailed kinetic studies using reaction progress kinetic analysis (RPKA) methods have provided insight into the factors influencing the reaction rate in terms of impact of ligand structure, reactant/catalyst dependence and catalyst (in)stability. These kinetic insights have been used in a quality‐by‐design approach for further optimization of the reaction protocol. The reaction scope was extended to 22 examples, showing broad applicability for a wide range of substituted aryl iodides with both primary and secondary amines.
Whey protein (WP) is a widely consumed nutritional supplement, known to enhance strength and muscle mass during resistance training (RT) regimens. Muscle protein anabolism is acutely elevated ...following RT, which is further enhanced by WP. As a result, there is reason to suggest that WP supplementation may be an effective nutritional strategy for restoring the acute loss of contractile function that occurs following strenuous RT. This systematic review and meta-analysis provides a synthesis of the literature to date, investigating the effect of WP supplementation on the recovery of contractile function in young, healthy adults. Eight studies, containing 13 randomised control trials (RCTs) were included in this review and meta-analysis, from which individual standardised effect sizes (ESs) were calculated, and a temporal overall ES was determined using a random-effects model. Whilst only half of the individual studies reported beneficial effects for WP, the high-quality evidence taken from the 13 RCTs was meta-analysed, yielding overall positive small to medium effects for WP from < 24 to 96 h (ES range = 0.4 to 0.7), for the temporal restoration of contractile function compared to the control treatment. Whilst the effects for WP were shown to be consistent over time, these results are limited to 13 RCTs, principally supporting the requirement for further comprehensive research in this area.
Objective: Medical thoracoscopy is recommended in the investigation of patients with exudative pleural effusions, especially when pleural fluid analysis is uninformative. The histological finding of ...‘nonspecific pleuritis/fibrosis’ is common in thoracoscopic biopsies and presents a great uncertainty for clinicians and patients as the long-term outcome of these patients is unclear, and anxieties about undiagnosed malignancy persist. Method: A retrospective case-note study of 142 patients who underwent medical thoracoscopy over a 58-month period in a tertiary referral centre with a high incidence of mesothelioma. Patients with ‘nonspecific pleuritis/fibrosis’ were followed up until death or for a mean (±SD) period of 21.3 (±12.0) months. Results: A definitive histological diagnosis was achieved in 98 (69%) patients. A total of 44 (31%) patients had ‘nonspecific pleuritis/fibrosis’. Five (12%) were subsequently diagnosed with malignant pleural disease after a mean interval of 9.8 (±4.6) months. All five patients had histologically confirmed mesothelioma. In 26 patients with ‘nonspecific pleuritis/fibrosis’, no cause for the pleural effusion was discovered. The false-negative rate of thoracoscopic biopsy for the detection of pleural malignancy was 5%, with a diagnostic sensitivity of 95% and negative predictive value of 90%. Pleural effusion recurrence was more frequently associated with a false-negative pleural biopsy result. However, there was no correlation with other patient characteristics or the thoracoscopist’s prediction based on macroscopic appearances. Conclusion: Thoracoscopic pleural biopsy is valuable in the diagnosis of pleural malignancies. Patients with ‘nonspecific pleuritis/fibrosis’ require follow-up as a malignant diagnosis (especially mesothelioma) may eventually be established in approximately 12% of cases.