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Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional study from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.
No full textBACKGROUND
In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high-risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes.
METHODS
Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared.
RESULTS
Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2-4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma.
CONCLUSIONS
In patients with high-risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype-specific regimens should be further validated
An International Multicenter Real-Life Prospective Study of Electronic Chromoendoscopy Score PICaSSO in Ulcerative Colitis.
No full textBACKGROUND & AIMS
Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes.
METHODS
In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy.
RESULTS
A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval [CI] 0.86-0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77-0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83-0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio [HR] 0.19 [0.11-0.33] and 0.22 [0.13-0.34], respectively),} as well as PICaSSO 4-8 (HR 0.25 [0.12-0.53] and 0.22 (0.12-0.39), respectively) and similar to histologic remission.
CONCLUSION
In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC
Clinical Characterisation of Asthma with Fungal Sensitisation in a South Indian Paediatric Cohort.
No full textThe biological role of fungi in the pathophysiology of asthma has attracted renewed attention during the last decade. The term severe asthma with fungal sensitisation (SAFS) was first introduced in 2006 and has since been recognised as a distinct clinical phenotype in adult asthma
Multicentre, longitudinal, observational cohort study to examine the relationship between neutrophil function and sepsis in adults and children with severe thermal injuries: a protocol for the Scientific Investigation of the Biological Pathways Following Thermal Injury-2 (SIFTI-2) study.
No full textINTRODUCTION
Burn-induced changes in the phenotype and function of neutrophils, cells which provide front-line protection against rapidly dividing bacterial infections, are emerging as potential biomarkers for the early prediction of sepsis. In a longitudinal study of adult burns patients, we recently demonstrated that a combined measurement of neutrophil phagocytic capacity, immature granulocyte (IG) count and plasma cell-free DNA (cfDNA) levels on the day of injury gave good discriminatory power for the prediction of later sepsis development. However, limited by a small sample size, single-centre design and focus on adult burns patients, these biomarkers require prospective validation in a larger patient cohort. The Scientific Investigation of the Biological Pathways Following Thermal Injury-2 study aims to prospectively validate neutrophil phagocytic activity, IG count and plasma cfDNA levels as early prognostic biomarkers of sepsis in thermally injured adult and paediatric patients.
METHODS AND ANALYSIS
This multicentre, longitudinal, observational cohort study will enrol 245 paediatric and adult patients with moderate to severe burns within 24 hours of injury. Blood samples will be obtained at 19 postinjury time points (days 1-14, day 28, months 3, 6, 12 and 24) and analysed for neutrophil phagocytic activity, IG count and cfDNA levels. Patients will be screened daily for sepsis using the 2007 American Burn Association diagnostic criteria for sepsis. In addition, daily multiple organ dysfunction syndrome and Sequential Organ Failure Assessment Scores will be recorded relationships between neutrophil phagocytic activity, IG count and plasma cfDNA levels on day 1 of injury and the development of sepsis will be examined using logistic regression models.
ETHICS AND DISSEMINATION
This study received ethics approval from the West Midlands, Coventry and Warwickshire Research Ethics Committee (REC reference:16/WM/0217). Findings will be presented at national and international conferences, and submitted for publication in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT04693442
SARS-CoV-2 environmental contamination from hospitalised patients with COVID-19 receiving aerosol-generating procedures.
No full textBACKGROUND
Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered 'aerosol-generating procedures' in the treatment of COVID-19.
OBJECTIVE
To measure air and surface environmental contamination with SARS-CoV-2 virus when CPAP and HFNO are used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients.
METHODS
30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturation ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. Real-time quantitative polymerase chain reaction analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus.
RESULTS
Overall 21/30 (70%) participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination than supplemental oxygen use. Only one nasopharyngeal sample was culture positive.
CONCLUSIONS
The use of CPAP and HFNO to treat moderate/severe COVID-19 did not appear to be associated with substantially higher levels of air or surface viral contamination in the immediate care environment, compared with the use of supplemental oxygen
Healthcare worker perceptions of routine asymptomatic SARS-CoV-2 screening using lateral flow assays: A qualitative analysis across two London hospitals.
No full textTHE IMPACT OF ATRIAL FIBRILLATION ON OUTCOMES OF PERIPHERAL ARTERIAL DISEASE: ANALYSIS OF ROUTINELY COLLECTED PRIMARY CARE DATA.
No full textBACKGROUND
The combination of peripheral arterial disease and atrial fibrillation is linked with high risk of mortality and stroke. This study aims to investigate the impact of atrial fibrillation on patients with diagnosed peripheral arterial disease.
METHODS
This is a retrospective study using The Health Improvement Network (THIN) database, which contains prospectively collected data from participating primary care practices. Patients with a new diagnosis of peripheral arterial disease between 01/08/1995 and 01/05/2017 were identified in the database alongside relevant demographic information, clinical history and medications. Every patient in the dataset with peripheral arterial disease and baseline atrial fibrillation (case), was matched to a patient without atrial fibrillation (control) with similar characteristics using propensity score matching. Cox-regression analysis was performed and hazard ratios (HR) calculated for the outcomes of death, stroke, ischaemic heart disease, heart failure and major amputation.
RESULTS
Prevalence of atrial fibrillation in this cohort was 10.2%. All patients with peripheral arterial disease and atrial fibrillation (n=5685) were matched with 5685 patients without atrial fibrillation but otherwise similar characteristics. After multivariate analysis, atrial fibrillation was independently associated with mortality (HR: 1.18, 95% Confidence Interval (CI) 1.12- 1.26, p< 0.01), cerebrovascular events (HR: 1.35, 95%CI 1.17- 1.57, p< 0.01) and heart failure (HR: 1.87, 95%CI 1.62- 2.15, p< 0.01) but not with ischaemic heart disease or limb loss.
CONCLUSION
In peripheral arterial disease patients, atrial fibrillation is a risk factor for mortality, stroke and heart failure. This emphasizes the need for proactive surveillance and holistic management of these patients
Outcomes of anterior interosseous nerve transfer to restore intrinsic muscle function after high ulnar nerve injury.
No full textTraumatic high ulnar nerve injuries have historically resulted in long-term loss of hand function due to the long re-innervation distance to the intrinsic muscles. Transfer of the anterior interosseous nerve (AIN) to the deep motor branch of the ulnar nerve (MUN) is proving promising in these patients. The purpose of this study was to evaluate the outcomes and efficacy of this procedure in our series. Eligible high ulnar nerve injury patients who underwent AIN to MUN nerve transfer were evaluated with a mean follow-up of 17 months. Data including demographics, injury details, surgical procedures, and outcomes were collected. A review of the current literature was performed for comparison. Sixteen patients had AIN to MUN transfer, mean age of 39.4 years, and a median delay from injury to nerve transfer of 0.8 months. The injury site was above the elbow in 5 cases, at the elbow in 8 cases, and in the proximal forearm in 3 cases. The majority were sharp transection, with the remaining from blast injuries, traumatic traction, and one post-traumatic neuroma resection. Transfer was performed end-to-end in 7 cases, hemi end-to-end in 7 cases, and supercharged end-to-side in 2 cases. Five patients achieved intrinsic muscle recovery of MRC 4+ and thirteen gained MRC 3 or above. The AIN to MUN nerve transfer provides meaningful intrinsic recovery in the majority of traumatic high ulnar nerve injuries. This procedure should be routinely considered, however, warrants further research to validate the optimum technique
ARTP statement on cardiopulmonary exercise testing 2021.
No full textCardiopulmonary exercise testing (CPET) has become an invaluable tool in healthcare, improving the diagnosis of disease and the quality, efficacy, assessment and safety of treatment across a range of pathologies. CPET's superior ability to measure the global exercise response of the respiratory, cardiovascular and skeletal muscle systems simultaneously in a time and cost-efficient manner has led to the application of CPET in a range of settings from diagnosis of disease to preoperative assessment. The Association for Respiratory Technology and Physiology Statement on Cardiopulmonary Exercise Testing 2021 provides the practitioner and scientist with an outstanding resource to support and enhance practice, from equipment to testing to leadership, helping them deliver a quality assured service for the benefit of all patient groups