In situ polymerization and electrical conductivity of polypyrrole/cellulose nanocomposites using Schweizer's reagent.

Cellulose-based composites have attracted interest given the shift towards 'green' materials, but achieving uniform dispersions of cellulose in polymer matrices and/or enhancement of interfacial interactions between components remains challenging. Herein we report the preparation of polypyrrole/cellulose nanocomposites in [Cu(NH3)4(H2O)2](OH)2 (Schweizer's reagent/cuoxam)-based reaction media via in situ polymerization. The effect of cellulose template morphology and reaction media on the microstructure, electrical conductivity, and surface wettability was studied. Aqueous reaction media favored the formation of a uniform polypyrrole coating encapsulating the cellulose fibers; concentrated cuoxam solutions promoted inhomogeneity and exhibited a progressive decline in conductivity. The maximum conductivity attained was 3.08 S cm-1 from a bacterial cellulose-templated composite prepared in aqueous reaction media and afforded an approximately threefold increase in conductivity when compared with pure PPy at 1.14 S cm-1. Generally, the composites resembled wetting surfaces - with highly concentrated cuoxam solutions yielding improved hydrophilicity, while substitution of bacterial cellulose with nanocrystalline cellulose engendered a shift towards hydrophobicity. Most composites displayed a contact angle of less than 90° suggesting PPy/cellulose composites tended towards hydrophilic behavior. This study highlights investigations into the viability of cellulose solvents as a facile means to control the structure and performance of in situ functionalized cellulose nanocomposites.

Radical cancer treatment is safe during COVID-19: the real-world experience of a large London-based Comprehensive Cancer Centre during the first wave.

BACKGROUND: During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection. METHODS: Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period. RESULTS: Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported. CONCLUSIONS: Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.

Maintaining safe lung cancer surgery during the COVID-19 pandemic in a global city.

BACKGROUND: SARS-CoV-2 has challenged health service provision worldwide. This work evaluates safe surgical pathways and standard operating procedures implemented in the high volume, global city of London during the first wave of SARS-CoV-2 infection. We also assess the safety of minimally invasive surgery(MIS) for anatomical lung resection. METHODS: This multicentre cohort study was conducted across all London thoracic surgical units, covering a catchment area of approximately 14.8 Million. A Pan-London Collaborative was created for data sharing and dissemination of protocols. All patients undergoing anatomical lung resection 1st March-1st June 2020 were included. Primary outcomes were SARS-CoV-2 infection, access to minimally invasive surgery, post-operative complication, length of intensive care and hospital stay (LOS), and death during follow up. FINDINGS: 352 patients underwent anatomical lung resection with a median age of 69 (IQR: 35-86) years. Self-isolation and pre-operative screening were implemented following the UK national lockdown. Pre-operative SARS-CoV-2 swabs were performed in 63.1% and CT imaging in 54.8%. 61.7% of cases were performed minimally invasively (MIS), compared to 59.9% pre pandemic. Median LOS was 6 days with a 30-day survival of 98.3% (comparable to a median LOS of 6 days and 30-day survival of 98.4% pre-pandemic). Significant complications developed in 7.3% of patients (Clavien-Dindo Grade 3-4) and 12 there were re-admissions(3.4%). Seven patients(2.0%) were diagnosed with SARS-CoV-2 infection, two of whom died (28.5%). INTERPRETATION: SARS-CoV-2 infection significantly increases morbidity and mortality in patients undergoing elective anatomical pulmonary resection. However, surgery can be safely undertaken via open and MIS approaches at the peak of a viral pandemic if precautionary measures are implemented. High volume surgery should continue during further viral peaks to minimise health service burden and potential harm to cancer patients. FUNDING: This work did not receive funding.

Continuity of Cancer Care: The Surgical Experience of Two Large Cancer Hubs in London and Milan.

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and <1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), <1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

External Compressive Bracing With Initial Reduction of Pectus Carinatum: Compliance Is the Key.

BACKGROUND: To assess the impact of manipulation and a tailored program for compressive bracing on the quality of life of patients with flexible pectus carinatum. METHODS: Two hundred forty-nine sequential patients attending a clinic for assessment of pectus carinatum deformities underwent outpatient manipulation and then followed a prescribed schedule of continuous external compressive bracing but without significant progressive tightening. RESULTS: There was successful sustained reduction of the deformity in 244 patients with high reported rates of concordance (98%) and satisfaction (94%). Patients experienced a reduction in symptoms of anxiety and depression (P < .001) and had improved body satisfaction (P < .001). Mild skin irritation occurred in 18% of patients (n = 44), and there were 2 severe cases of skin irritation, 1 of which resulted in abandonment of bracing. CONCLUSIONS: Manipulation and nontightening compressive bracing was associated with complete concordance, high levels of successful bracing, improved confidence, and reduced psychological morbidity.

Initial reduction of flexible pectus carinatum with outpatient manipulation as an adjunct to external compressive bracing: technique and early outcomes at 12 weeks.

INTRODUCTION: Our aim was to assess whether initial reduction with outpatient soft-tissue manipulation of flexible pectus carinatum deformity prior to external compressive bracing was associated with improved compliance and patient satisfaction compared to reported outcomes of external brace with progressive tightening. MATERIALS AND METHODS: From our observational cohort of 227 patients, 177 were felt appropriate to undergo initial reduction and soft tissue manipulation prior to immediate custom fitting of an external compressive brace. These patients then followed a prescriptive schedule of 12 weeks of continuous external bracing with subsequent follow-up in clinic. RESULTS: The reduction in Haller Index was maintained throughout the period of external bracing without the need for progressive tightening of the external brace. The treatment was associated with high levels of patient satisfaction and high patient concordance compared to other protocols. There were no major complications and minor complications included only skin irritation. CONCLUSIONS: Out-patient initial reduction with manipulation prior to external compressive bracing is a novel technique which resulted in excellent concordance and high rates of patient satisfaction and should be considered as an adjunct to standard external bracing techniques. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level II.

2018 White Paper on Recent Issues in Bioanalysis: 'A global bioanalytical community perspective on last decade of incurred samples reanalysis (ISR)' (Part 1 - small molecule regulated bioanalysis, small molecule biomarkers, peptides & oligonucleotide bioanalysis).

The 2018 12th Workshop on Recent Issues in Bioanalysis (12th WRIB) took place in Philadelphia, PA, USA on April 9-13, 2018 with an attendance of over 900 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day full immersion in bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule bioanalysis involving LC-MS, hybrid ligand binding assay (LBA)/LC-MS and LBA/cell-based assays approaches. This 2018 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2018 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for LC-MS for small molecules, peptides, oligonucleotides and small molecule biomarkers. Part 2 (hybrid LBA/LC-MS for biotherapeutics and regulatory agencies' inputs) and Part 3 (large molecule bioanalysis, biomarkers and immunogenicity using LBA and cell-based assays) are published in volume 10 of Bioanalysis, issues 23 and 24 (2018), respectively.

Current practices and future outlook on the integration of biomarkers in the drug development process.

Over the last decade, there has been broad incorporation of translational biomarkers into the early drug development process to predict safety concerns, measure target engagement and monitor disease progression. One goal of translational biomarkers is to create a cycle whereby preclinical readouts influence candidate selection and subsequent clinical data are fed back into research to facilitate better decision making. Successes have been limited and not as broad in scope as desired. Collaborations between industry and regulators have increased the number of qualified biomarkers; but the process is lengthy and expensive. A high level overview of translational biomarkers as well as a discussion of some of the successes and failures encountered in development is discussed here.

Quantitative analysis of four protein biomarkers: An automated microfluidic cartridge-based method and its comparison to colorimetric ELISA.

Biomarker quantitation with ligand binding assays has matured greatly in recent years. This maturation has been partly in response to demands for more data points from fewer samples or less available sample volume. Multiplexing offers opportunities to acquire data for multiple analytes from single sample assay iterations, but has its own unique challenges and limitations. ProteinSimple has developed Simple Plex™, an automated immunoassay platform consisting of microfluidic cartridge-based assays run on the Ella instrument. Ella subverts traditional multiplexing challenges by rapidly performing triplicate measurements of up to four different analytes simultaneously, each in their own respective assay vessels and all from a single sample. Here we describe a comparison of the Simple Plex platform versus colorimetric ELISA and their respective abilities to quantitate four common biomarkers (MCP-1/CCL2, VEGF-A, TNF-α, and IL-6) from twenty-eight healthy individual donor plasma samples. Each biomarker was tested on the two platforms on each of two days. Ella analysis required significantly reduced sample volume, manual steps, and total time. Overall, Ella was able to quantify results for all twenty-eight samples for each of the four biomarkers. In contrast, ELISA was able to measure quantifiable results within respective calibration curve ranges for MCP-1/CCL2 (96% of samples) and VEGFA (7% of samples). For TNF-α and IL-6, ELISA was not sensitive enough to quantify any samples in the assay ranges. This stark difference in quantitative results underscores Ella's ability to multiplex without compromising sensitivity, and has far reaching potential for biomarker panel measurement in support of diagnosis, prognosis, and monitoring of disease.

Is surgery indicated in patients with stage IIIa lung cancer and mediastinal nodal involvement?

The role of surgery in the treatment of patients with stage IIIa non-small cell lung cancer (NSCLC) and mediastinal node involvement is examined in this best evidence topic according to a structured protocol. A total of 579 papers were identified using the outlined search, 12 of which were deemed to represent the best available evidence. From the data summarized, we conclude that surgery, as part of a multimodality therapeutic approach, offers a survival benefit for patients with resectable N2 NSCLC. Overall five-year survival rates following primary resection ranged from 17% to 20% (four studies). Improved five-year survival was demonstrated with multimodality therapy (19-45%; 13 studies). Subgroup analysis demonstrates a five-year survival of 30.5% with postoperative chemo-radiotherapy, 22.2% with chemotherapy alone, and 27% with radiotherapy alone. In our review, we address three major issues regarding the management of stage IIIa NSCLC, the first of which is primary vs. postinduction surgery. The largest cohort series to date is the International Association for the Study of Lung Cancer Staging Committee paper on nodal disease, which reports that patients with single-zone N2 disease had the same survival outcome as patients with multizone N1 disease. The second issue is that of randomized vs. cohort studies: there have been five randomized trials reporting similar outcomes and hence equipoise. The third issue is postinduction staging. All studies evaluated reported a better outcome in patients with ypN0 (i.e. postinduction N0 disease). However, surgery should not be denied to patients with ypN1-N2, as there is evidence to demonstrate a significant improvement in survival time in all patients able to undergo surgery after induction chemo-radiotherapy. In conclusion, although some of the evidence available is equivocal regarding the survival benefit of resection for stage IIIa N2 disease, the authors believe surgery should be considered as part of a multimodality therapeutic strategy for patients with advanced nodal disease.

Videoendoscopic resection of solitary peripheral lung nodule.

Minimally invasive surgery has transformed the management of peripheral lung nodules. In this interactive guide, we describe an evidence-based approach to video-assisted thoracic surgery (VATS) resection with a step-by-step operative guide.

Methicillin-resistant Staphylococcus aureus in surgical patients: identification of high-risk populations for the development of targeted screening programmes.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA)-related hospital-acquired infection (HAI) in surgical patients is associated with high morbidity, mortality and financial cost. The identification and characterisation of populations of patients who are at high risk of developing MRSA infection or colonisation could inform the design of more effective strategies to prevent HAIs and reduce transmission of MRSA. PATIENTS AND METHODS: An analysis of historical discharge data for the whole of 2005 (7145 surgical in-patients) was performed, for all patients admitted to general surgery at the Royal Infirmary of Edinburgh. Analysis specifically focused on MRSA laboratory data and coding data for patient demographics, medical co-morbidities, and progress of in-patient stay. RESULTS: A total of 134 (1.88%) individual patients with colonisation or infection by MRSA were identified from indicated laboratory testing. Univariate analysis identified a significant association of concurrent MRSA-positive status with patients aged over 60 years (P < 0.01), a duration of inpatient stay > 7 days (P < 0.01), presence of a malignant neoplasm (P < 0.01), circulatory disease (P < 0.01), respiratory disease (P < 0.01), central nervous system disease (P < 0.01), renal failure (P < 0.01), and concurrent admission to ITU/HDU (P < 0.01). Multivariate analysis suggested MRSA colonisation or infection was strongest in those with co-morbid malignancy (P < 0.0001) or admission to ITU/HDU (P < 0.0001). CONCLUSIONS: This large observational study has identified cancer patients as a UK surgical patient subpopulation which is at significantly higher risk of colonisation by MRSA. These data could inform the development of focused hospital in-patient screening protocols and provide a means to stratify patient risk.