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Utility of volatile organic compounds as a diagnostic tool in preterm infants.
No full textBACKGROUND
Volatile organic compounds (VOCs) are hydrocarbons that originate within different healthy and diseased tissues. VOCs can be secreted into the circulation and then excreted in the urine and faeces. In the lungs, VOCs are locally produced and can be detected in exhaled breath. VOCs can be identified using non-invasive techniques, which make their use in preterm infants safe and desirable.
METHODS
A systematic search of the literature in PubMed, Embase and Web of Science was conducted looking for VOCs techniques and diagnostic performance in preterm infants. A total of 50 articles identified with only seven papers were included in the final analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
VOCs could diagnose necrotising enterocolitis up to 4 days before a clinical diagnosis; for late onset sepsis, up to 3 days before; and for bronchopulmonary dysplasia, up to 2 weeks before. In addition to these diagnostic uses, VOCs analysis could also distinguish breastfed from formula-fed preterm neonates in the first month of life.
CONCLUSION
VOCs analysis is a non-invasive tool that makes the use in preterm infants of preference. VOCs analytic techniques require more research and consensus between researchers to overcome their limitations.
IMPACT
Volatile organic compounds are hydrocarbons that can separate between healthy and diseased states in preterm infants.Biomarker panels developed from volatile organic compounds are potential diagnostic tools.The non-invasive nature of acquiring volatile organic compounds markers make it desirable in the paediatric patients.Research into exact chemical components of the volatile organic compounds can inform about the pathophysiology of disease in preterm infants.More robust longitudinal studies with repeated experiments are required before volatile organic compounds can be applied in clinical practice
Impact of postoperative complications on survival after oesophagectomy for oesophageal cancer.
No full textBACKGROUND
Recent evidence suggests that complications after oesophagectomy may decrease short- and long-term survival of patients with oesophageal cancer. This study aimed to analyse the impact of complications on survival in a Western cohort.
METHODS
Complications after oesophagectomy were recorded for all patients operated on between January 2006 and February 2017, with severity defined using the Clavien-Dindo classification. Associations between complications and overall and recurrence-free survival were assessed using univariable and multivariable Cox regression models.
RESULTS
Of 430 patients, 292 (67·9 per cent) developed postoperative complications, with 128 (39·8 per cent) classified as Clavien-Dindo grade III or IV. No significant associations were detected between Clavien-Dindo grade and either tumour (T) (P = 0·071) or nodal (N) status (P = 0·882). There was a significant correlation between Clavien-Dindo grade and ASA fitness grade (P = 0·032). In multivariable analysis, overall survival in patients with Clavien-Dindo grade I complications was similar to that in patients with no complications (hazard ratio (HR) 0·97, P = 0·915). However, patients with grade II and IV complications had significantly shorter overall survival than those with no complications: HR 1·64 (P = 0·007) and 1·74 (P = 0·013) respectively.
CONCLUSION
Increasing severity of complications after oesophagectomy was associated with decreased overall survival. Prevention of complications should improve survival
Myocardial Edema, Myocyte Injury, and Disease Severity in Fabry Disease.
No full textBackground Cardiovascular magnetic resonance can demonstrate myocardial processes in Fabry disease (FD), such as low native T1 (sphingolipid storage) and late gadolinium enhancement (LGE, scar). Recently, high T2 (edema) has been observed in the basal inferolateral wall along with troponin elevation. We hypothesized that edema and myocyte injury would be chronically associated and have electrical, mechanical, and disease associations in FD. Methods A prospective international multicenter study was conducted on 186 consecutive FD patients (45.2±1.1 years, 58% females). Additionally, 28 patients with hypertrophic cardiomyopathy, 30 with chronic myocardial infarction and 59 healthy volunteers were included. All study participants underwent comprehensive cardiovascular magnetic resonance with T1 and T2 mapping, cines, and LGE imaging. Results LGE in the basal inferolateral wall in FD had T2 elevation (FD 58.2±5.0 ms versus hypertrophic cardiomyopathy 55.6±4.3 ms, chronic myocardial infarction 53.7±3.4 ms and healthy volunteers 48.9±2.5 ms, 20%, =0.034). Conclusions LGE in Fabry has chronic local T2 elevation that is strongly associated with chronic troponin elevation. In addition, there is slight global T2 elevation. Both are associated with ECG and mechanical changes and clinical worsening over 1 year
Birmingham mandible and midface rules: determining variables for inclusion in a clinical predictor rule.
No full textStaff in emergency departments often rely on heuristics and algorithms to make clinical decisions on a wide range of problems. Clinical predictor rules such as the Ottawa ankle rules serve to reduce the need for unnecessary radiographs and help to give frontline staff the confidence to make a diagnosis. The current study aimed to achieve consensus on the variables to test for inclusion in a set of predictor rules for suspected fractures of the mandible and midface. A three-stage modified Delphi study was conducted of members and fellows of the British Association of Oral and Maxillofacial Surgeons (BAOMS). At the third stage, there was agreement of more than 51% to retain 11/35 of the suggested predictors for mandibular fractures and 14/28 of the midface predictors. To develop and validate clinical predictor rules for use by frontline staff, these variables will now form part of a prospective data gathering exercise at a major trauma centre
Sensitivity and Specificity of SkinVision are likely to have been overestimated.
No full textUdrea et al [1] reported 95.1% sensitivity and 78.3% specificity using the SkinVision app for risk assessment of skin lesions. These are likely to be overestimates due to the nature of the study design and flaws in sampling
Entomology contributing to the study of undiagnosed non-malarial undifferentiated febrile illnesses in South Sudan.
No full textAutophagy occurs in lymphocytes infiltrating Sjögren's syndrome minor salivary glands and correlates with histological severity of salivary gland lesions.
No full textBACKGROUNDS
The organization of minor salivary glands (MSG) infiltrates, in patients with Sjögren's syndrome (SS), associates with disease severity and progression. Aberrant regulation of lymphocyte autophagy is involved in autoimmunity, and in previous work, we provided the first evidence of upregulated autophagy in CD4+ T cells infiltrating SS MSG. The aim of this study was to further explore autophagy in SS infiltrating and circulating lymphocytes and to investigate its role in disease histopathological progression.
METHODS
After collection of 20 SS MSG, the presence of lymphocyte aggregates (foci) and the formation of germinal center (GC)-like structures were observed by H&E and confirmed by immunohistochemistry. The expression of autophagy-related genes, Atg5 and MAP1LC3A, was detected by RT-PCR on microdissected salivary gland tissue and control tonsils. In MSG and tonsils, autophagic lymphocytes were identified by the detection of the autophagosome protein LC3B visualized as LC3 puncta staining by immunofluorescence. Peripheral blood autophagy was assessed by flow cytometry in SS and healthy controls (HC).
RESULTS
Real-time PCR demonstrated higher expression in the autophagy genes Atg5 and MAP1LC3A in MSG GCs as compared to both small foci (p = 0.0075, p = 0.0002) and GCs from tonsils (p = 0.0001, p = 0.0037). In MSG, LC3 puncta staining was detectable on both CD3+ and CD20+ lymphocytes; in tonsils, LC3 puncta was almost undetectable on all lymphocytes. Compared to HC (n = 20), flow cytometry did not reveal any increase of autophagy in SS circulating lymphocytes (n = 30).
CONCLUSIONS
In SS MSG, lymphocytes' autophagy is a feature of infiltrating T and B cells and is associated with histological severity. Interestingly, in MSG aberrant regulation of autophagy is detectable in GC-like structures possibly indicating its involvement in the development and persistence of the autoimmune process within the lesions
Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with cisplatin in patients with head and neck cancer: the trial protocol.
No full textINTRODUCTION
Patients with head and neck squamous cell carcinoma with locally advanced disease often require multimodality treatment with surgery, radiotherapy and/or chemotherapy. Adjuvant radiotherapy with concurrent chemotherapy is offered to patients with high-risk pathological features postsurgery. While cure rates are improved, overall survival remains suboptimal and treatment has a significant negative impact on quality of life.Cell cycle checkpoint kinase inhibition is a promising method to selectively potentiate the therapeutic effects of chemoradiation. Our hypothesis is that combining chemoradiation with a WEE1 inhibitor will affect the biological response to DNA damage caused by cisplatin and radiation, thereby enhancing clinical outcomes, without increased toxicity. This trial explores the associated effect of WEE1 kinase inhibitor adavosertib (AZD1775).
METHODS AND ANALYSIS
This phase I dose-finding, open-label, multicentre trial aims to determine the highest safe dose of AZD1775 in combination with cisplatin chemotherapy preoperatively (group A) as a window of opportunity trial, and in combination with postoperative cisplatin-based chemoradiation (group B).Modified time-to-event continual reassessment method will determine the recommended dose, recruiting up to 21 patients per group. Primary outcomes are recommended doses with predefined target dose-limiting toxicity probabilities of 25% monitored up to 42 days (group A), and 30% monitored up to 12 weeks (group B). Secondary outcomes are disease-free survival times (groups A and B). Exploratory objectives are evaluation of pharmacodynamic (PD) effects, identification and correlation of potential biomarkers with PD markers of DNA damage, determine rate of resection status and surgical complications for group A; and quality of life in group B.
ETHICS AND DISSEMINATION
Research Ethics Committee, Edgbaston, West Midlands (REC reference 16/WM/0501) initial approval received on 18/01/2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences.
TRIAL REGISTRATION NUMBER
ISRCTN76291951 and NCT03028766
Outcome of Hospitalization for COVID-19 in Patients with Interstitial Lung Disease. An International Multicenter Study.
No full textThe impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death. Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71). Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD
Isolating polysaccharide IgG pneumococcal antibody responses by pre-adsorption of conjugate vaccine serotypes: A modified approach for the conjugate vaccine era.
No full textBACKGROUND
Assessment of pure polysaccharide response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be biased by previous exposure to the conjugate vaccine (PCV). We applied pre-analytical modification to the existing ELISA by pre-incubating serum with PCV.
METHODS
PCV-adsorbed and non-adsorbed sera were prepared before measuring the concentration of anti-pneumococcal capsular polysaccharide (PCP) IgG antibodies by the whole pneumococcal ELISA. Paired pre and post-pneumococcal vaccination sera from 73 subjects were analyzed and the baseline anti-PCP IgG for each sample was subtracted from the post-vaccination value to measure vaccine responses. Absolute change in titers and fold changes were then compared between both methods.
RESULTS
In the PCV-vaccinated group (n = 28), pre-adsorption with PCV significantly reduced the vaccine responses compared to non-adsorbed sera [median increase in anti-PCP titers: 27.55 mg/l and 45.98 mg/l, respectively]. In addition, the median fold change dropped significantly from 3.026 to 2.313. In PPV23-vaccinated immunocompetent subjects (n = 28) there was a significant difference in anti-PCP responses with PCV adsorption [median values: 73.71 mg/l without and 51.04 mg/l with adsorption]. All the antibody deficiency patients (n = 17) displayed poor PPV23 responses. Although PPV23 responsiveness was not statistically different between both methods, we have observed a trend for lower anti-PCP IgG titers in PCV-adsorbed sera compared to non-adsorbed ones. Serotype-specific IgG analysis using a multiplexed bead-based immunoassay performed on 10 paired samples confirmed that the adsorption observed is specific to PCV serotypes.
CONCLUSION
Pre-analytical modification to the conventional ELISA by removing the PCV-specific serotypes may differentiate true polysaccharide response from recall response induced by previous PCV vaccination