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Circulating tumour cells and tumour biomarkers in functional midgut neuroendocrine tumours.
No full textCALM-NET was a phase IV exploratory study in the UK that aimed to evaluate if the presence of circulating tumour cells (CTCs) at baseline predicted symptomatic response in patients with midgut neuroendocrine tumours (NETs) treated with lanreotide autogel (LAN). Adults with functional, well/moderately differentiated (Ki-67 0. Primary endpoint was the clinical value of baseline CTCs to predict symptomatic response (decrease in diarrhoea or flushing of ≥50% frequency, or ≥1 severity level). Other endpoints included progression-free survival (PFS) and correlations between plasma and urinary biomarkers (including 5-hydroxyindoleacetic acid [5-HIAA]). Fifty patients were enrolled; 40 completed the study. Baseline CTCs were present in 22 (45.8%) patients (missing baseline CTC status n = 2). Overall, 87.5% (95% confidence interval [CI]: 73.9; 94.5) of patients had a symptomatic response; a 5.9-fold higher odds of symptomatic response in patients without CTC versus patients with CTC at baseline was observed, although this was not statistically significant (odds ratio: 0.17 [95% CI: 0.02; 1.65], p = .126). One-year PFS rate was 66.4% (95% CI: 48.8; 79.2). Biomarker concentrations did not correlate to baseline CTC status. However, there was a strong correlation between plasma and urinary 5-HIAA (Spearman correlation coefficients ≥0.87 [p < .001], all time points). In conclusion, patients without CTC at baseline may be more likely to achieve a symptomatic response following LAN treatment than patients with CTC. Plasma 5-HIAA correlated with urinary 5-HIAA during LAN treatment. ClinicalTrials.gov identifier: NCT02075606
Nationwide evaluation of the advanced clinical practitioner role in England: a cross-sectional survey.
No full textBACKGROUND AND STUDY OBJECTIVE
In response to growing pressures on healthcare systems, the advanced clinical practice (ACP) role has been implemented widely in the UK and internationally. In England, ACP is a level of practice applicable across various healthcare professions, who exercise a level of autonomy across four domains, referred to as the four pillars of practice (education, leadership, research and clinical practice). A national framework for ACP was established in 2017 to ensure consistency across the ACP role, however current ACP governance, education and support is yet to be evaluated. This study aimed to analyse data from a national survey of the ACP role to inform the development and improvement of policies relating to ACP in the National Health Service (NHS) in England.
DESIGN
A cross-sectional survey with free-text comments.
SETTING
The survey was distributed across primary and secondary levels of care to three distinct groups in England, including individual ACPs, NHS provider organisations and Trusts and primary care settings.
PARTICIPANTS
A total of 4365 surveys were returned, from ACP staff (n=4013), NHS provider organisations and Trusts (n=166) and primary care organisations (n=186).
RESULTS
Considerable variation was found in role titles, scope of practice, job descriptions and educational backgrounds of ACPs. Differing approaches to governance were noted, which led to inconsistent ACP frameworks in some organisations. A further challenge highlighted included committing time to work across the four pillars of advanced practice, particularly the research pillar. ACPs called for improvements in supervision and continuing professional development alongside further support in navigating career pathways.
CONCLUSIONS
A standardised approach may support ACP workforce development in England and enable ACPs to work across the four pillars of practice. Due to the wide uptake of ACP roles internationally, this study has relevance across professions for global healthcare workforce transformation
CACONET: a novel classification framework for microbial correlation networks.
No full textMOTIVATION
Existing microbiome-based disease prediction relies on the ability of machine learning methods to differentiate disease from healthy subjects based on the observed taxa abundance across samples. Despite numerous microbes have been implicated as potential biomarkers, challenges remain due to not only the statistical nature of microbiome data, but also the lack of understanding of microbial interactions which can be indicative of the disease.
RESULTS
We propose CACONET (classification of Compositional-Aware COrrelation NETworks), a computational framework that learns to classify microbial correlation networks and extracts potential signature interactions, taking as input taxa relative abundance across samples and their health status. By using Bayesian compositional-aware correlation inference, a collection of posterior correlation networks can be drawn and used for graph-level classification, thus incorporating uncertainty in the estimates. CACONET then employs a deep learning approach for graph classification, achieving excellent performance metrics by exploiting the correlation structure. We test the framework on both simulated data and a large real-world dataset pertaining to microbiome samples of colorectal cancer (CRC) and healthy subjects, and identify potential network substructure characteristic of CRC microbiota. CACONET is customizable and can be adapted to further improve its utility.
AVAILABILITY
CACONET is available at https://github.com/yuanwxu/corr-net-classify.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online
Evidence base for investigative and therapeutic modalities in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.
No full textChronic inflammatory demyelinating polyneuropathy, its variants and multifocal motor neuropathy belong to a spectrum of peripheral nerve disorders with complex dysimmune disease mechanisms. Awareness of the unique clinical phenotypes but also heterogeneity between patients is vital to arrive at early suspicion and ordering appropriate tests. This includes requirements for optimal electrodiagnostic protocol, aimed to capture sufficient electrophysiologic evidence for relevant abnormalities, a case-based approach on the eventual need to further expand the diagnostic armamentarium and correct reading of their results. Considerable phenotypical variation, diverse combinations of abnormalities found on diagnostic tests and heterogeneity in disease course and treatment response, all contribute to widespread differences in success rates on timely diagnosis and optimal treatment. We aim to provide a practical overview and guidance on relevant diagnostic and management strategies, including pitfalls and present a summary of the relevant novel developments in this field
Delirium and COVID-19: a narrative review of emerging evidence.
No full textDelirium is a common condition affecting hospital inpatients, including those having surgery and on the intensive care unit. Delirium is also common in patients with COVID-19 in hospital settings, and the occurrence is higher than expected for similar infections. The short-term outcomes of those with COVID-19 delirium are similar to that of classical delirium and include increased length of stay and increased mortality. Management of delirium in COVID-19 in the context of a global pandemic is limited by the severity of the syndrome and compounded by the environmental constraints. Practical management includes effective screening, early identification and appropriate treatment aimed at minimising complications and timely escalation decisions. The pandemic has played out on the national stage and the effect of delirium on patients, relatives and healthcare workers remains unknown but evidence from the previous SARS outbreak suggests there may be long-lasting psychological damage
Urine DNA for monitoring chemoradiotherapy response in muscle-invasive bladder cancer: a pilot study.
No full textWSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections.
No full textSkin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs.An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds
Visual deterioration in patients with photoreceptor loss after retinal reattachment surgery.
No full textPURPOSE
Assess the relationship between photoreceptor degeneration and visual function after retinal reattachment surgery (RRS) in a prospective cohort.
METHODS
Patients with rhegmatogenous retinal detachment (RRD) were reviewed before and 6 months after vitreoretinal surgery. Optical coherence tomographical thickness of the outer nuclear layer (ONL), outer retinal segment (ORS), retinal pigmented epithelium to ellipsoid zone (RPE-EZ) and external limiting membrane to EZ (ELM-EZ) were recorded 6 months post-operatively. These were compared to best corrected visual acuity (BCVA) and retinal sensitivity (Humphrey visual field).
RESULTS
Thirteen macula-off and 8 macula-on RRD patients were included. The mean ONL thickness was higher after macula-on RRD compared to macula-off RRD (97.70 ± 3.62 μm vs. 73.10 ± 4.98 μm). In all RRD eyes, every 1 μm decrease in ONL thickness correlated with a 0.052 dB decrease and in retinal sensitivity and every 1 μm decrease in ORS thickness was associated with a 0.062 dB reduction in retinal sensitivity. ORS, ELM-EZ and RPE-EZ thickness did not correlate with BCVA post-RRS.
CONCLUSION
There was greater ONL and ORS thinning following macula-off compared to macula-on RRD. Correlations between ONL and ORS thinning with decreased retinal sensitivity may be explained by RRD-induced photoreceptor death
Sjögren's and non-Sjögren's sicca share a similar symptom burden but with a distinct symptom-associated proteomic signature.
No full textOBJECTIVES
Given the similarity in symptoms between primary Sjogren's syndrome (SjS) and non-SjS sicca syndrome (sicca), we sought to characterise clinical and proteomic predictors of symptoms in both groups in order to better understand disease mechanisms and help guide development of immunomodulatory treatments. These have not, to date, unequivocally improved symptoms in SjS clinical trials.
METHODS
Serum proteomics was performed using O-link inflammation and cardiovascular II panels. SjS (n=53) fulfilled 2016 ACR/European Alliance of Associations for Rheumatology (EULAR) criteria whereas sicca (n=60) were anti-Ro negative, displayed objective or subjective dryness, and either had a negative salivary gland biopsy or, in the absence of a biopsy, it was considered that a biopsy result would not change classification status. Linear regression analysis was performed to identify the key predictors of symptoms. Cluster analysis was completed using protein expression values.
RESULTS
EULAR-Sjögren's-Syndrome-Patient-Reported-Index (ESSPRI), EuroQoL-5 Dimension utility values, and anxiety and depression did not differ between SjS and sicca. Correlations between body mass index (BMI) and ESSPRI were found in sicca and to a lesser extent in SjS. Twenty proteins positively associated with symptoms in sicca but none in SjS. We identified two proteomically defined subgroups in sicca and two in SjS that differed in symptom burden. Within hierarchical clustering of the SjS and sicca pool, the highest symptom burden groups were the least distinct. Levels of adrenomedullin (ADM), soluble CD40 (CD40) and spondin 2 (SPON2) together explained 51% of symptom variability in sicca. ADM was strongly correlated with ESSPRI (spearman's r=0.62; p<0.0001), even in a multivariate model corrected for BMI, age, objective dryness, depression and anxiety scores.
CONCLUSIONS
Obesity-related metabolic factors may regulate symptoms in sicca. Further work should explore non-inflammatory drivers of high symptom burden in SjS to improve clinical trial outcomes
Incidental gallbladder cancer diagnosis confers survival advantage irrespective of tumour stage and characteristics.
No full textBACKGROUND
Incidental gallbladder cancer (IGBC) represents 50%-60% of gallbladder cancer cases. Data are conflicting on the role of IGBC diagnosis in oncological outcomes. Some studies suggest that IGBC diagnosis does not affect outcomes, while others that overall survival (OS) is longer in these cases compared to non-incidental diagnosis (NIGBC). Furthermore, some studies reported early tumour stages and histopathologic characteristics as possible confounders, while others not.
AIM
To investigate the role of IGBC diagnosis on patients' overall survival, especially after surgical treatment with curative intent.
METHODS
Retrospective analysis of all patient referrals with gallbladder cancer between 2008 and 2020 in a tertiary hepatobiliary centre. Statistical comparison of patient and tumour characteristics between IGBC and NIGBC subgroups was performed. Survival analysis for the whole cohort, surgical and non-surgical subgroups was done with the Kaplan-Meier method and the use of log rank test. Risk analysis was performed with univariable and multivariable Cox regression analysis.
RESULTS
The cohort included 261 patients with gallbladder cancer. 65% of cases had NIGBC and 35% had IGBC. A total of 90 patients received surgical treatment (66% of IGBC cases and 19% of NIGBC cases). NIGBC patients had more advanced T stage and required more extensive resections than IGBC ones. OS was longer in patients with IGBC in the whole cohort (29 4 mo, < 0.001), as well as in the non-surgical (14 2 mo, < 0.001) and surgical subgroups (29 16.5 mo, = 0.001). Disease free survival (DFS) after surgery was longer in patients with IGBC (21.5 mo 8.5 mo, = 0.007). N stage and resection margin status were identified as independent predictors of OS and DFS. NIGBC diagnosis was identified as an independent predictor of OS.
CONCLUSION
IGBC diagnosis may confer a survival advantage independently of the pathological stage and tumour characteristics. Prospective studies are required to further investigate this, including detailed pathological analysis and molecular gene expression