Synthesis of dispersants to generate fillers for composites designed to have an enhanced echogenic response

Ultrasound (US) imaging was identified as an advantageous imaging modality over the typically used X-ray. Thus, composites comprising of dispersed US-visible contrast agents embedded in a thermoplastic polyurethane matrix were made. To form the composite device, a commercially available material was used as a dispersant for microparticles. These coated phosphate-based glass microspheres were used as ultrasound visible contrast agents, in a medical grade polymer matrix. Ultrasound images of hollow tubes were obtained by Children’s National Medical Center (Washington DC, USA), which proved to show promising initial results. Imaging artefacts attributed to poor dispersion were observed, thus optimisation of device focussed on dispersant design. To optimise the dispersion of contrast agent throughout medical devices, bespoke dispersants were designed and synthesised to be more compatible with the matrix polymer. The first technique was to employ a thiol chain transfer agent (CTA) which was a one-pot, high yielding reaction to produce oligomers. The other method was catalytic chain transfer polymerisation (CCTP) followed by post-functionalisation of the vinyl-terminated oligomeric product via thiolene click chemistry. It was found that carboxylic acid containing thiols were excellent CTAs for monomers detailed. The synthesis of various iron-a-diimine complexes as potential alternatives to commercially available cobalt-based complexes that are typically used as control agents in catalytic chain transfer polymerisation (CCTP) was carried out. Their efficiency as chain transfer agents was investigated and related to the catalyst generation method, concentration and heating type. Although they did not exhibit high efficiencies as catalytic chain transfer agents under the conditions described, chain transfer behaviour was observed for these complexes. It was noted that molecular weight and dispersity of polymer products were lower than products obtained from uncontrolled free radical polymerisations. The differential effects of utilising microwave heating (MWH) on the rate and molecular composition of final products obtained compared to when conventionally heating (CH) was applied was also investigated. The differences were found to be related to an increase in the rate of propagation in the case of MWH conditions, which was attributed to the selective heating of particular radical species. Higher molecular weight polymers were obtained from MWH reactions, with the dispersity remaining relatively equivalent to those of the products obtained from analogous CH reactions. This suggests the selective heating of the propagating polymer radical dominated in this CCTP system rather than additional heating of the iron complex. The latter having been proposed as a potential route that electromagnetic waves may have increased the efficiencies of the iron-based catalysts due to their ferromagnetic centre in comparison to the paramagnetic cobalt complexes

Angiosome specific revascularisation: does the evidence support it?

Objective To explain the angiosome concept and explore the practical application of the angiosome literature to a clinical scenario, in this case a tibial angioplasty for critical ischaemia. Methods Clinical vignette with explanation of the decisions made and subsequent clinical results based on the theory of the angiosome concept and the literature on angiosomal revascularisation; in this case the results of our group’s recent update to a systematic review and meta-analysis. Results Endovascular combined or direct angiosomal revascularisation if superior to indirect revascularisation. This was borne out in the clinical scenario, where an indirect peroneal reperfusion of the AT angiosome resulted in major amputation. Open surgery is less dependent on the angiosome concept. The presence of adequate collateralisation into a foot arch seems to be the most important factor predicting success of indirect revascularisation. The evidence for both suffers from selection bias and many of the findings in the literature are wholly due to selection bias. Conclusion The angiosome concept is useful during both open and endovascular tibial revascularisation. However, the runoff in the foot is critical to success and may not follow the ‘classic’ angiosome model in diabetes

Facile Synthesis of Functionalised Hyperbranched Polymers for Application as Novel, Low Viscosity Lubricant Formulation Components

A novel, previously unreported, method for synthesising hyperbranched (HB) materials is detailed. Their use as additives to produce lubricant formulations that exhibit enhanced levels of wear protection and improved low-temperature oil viscosity and flow is also reported. The lubricant formulations containing HB additives were found to exhibit both significantly lower viscosities and improved in-use film-forming properties than the current industry standard formulations. To achieve this, alkyl methacrylate oligomers (predominantly dimers and trimers) were synthesised using catalytic chain transfer polymerisation. These were then used as functional chain transfer agents (CTA) to control the polymerisation of divinyl benzene (DVB) monomers to generate highly soluble, high polydispersity HB polymers. The level of dimer/trimer purification applied was varied to define its influence on both these HB resultant structures and the resultant HB additives’ performance as a lubricant additive. It was shown that, while the DVB acted as the backbone of the HB, the base oil solubility of the additive was imparted by the presence of the alkyl chains included in the structure via the use of the oligomeric CTAs

Application of targeted molecular and material property optimization to bacterial attachment-resistant (meth)acrylate polymers

Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the “hit” monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed

2-Year Change in Revised Hammersmith Scale Scores in a Large Cohort of Untreated Paediatric Type 2 and 3 SMA Participants

The Revised Hammersmith Scale (RHS) is a 36-item ordinal scale developed using clinical expertise and sound psychometrics to investigate motor function in participants with Spinal Muscular Atrophy (SMA). In this study, we investigate median change in the RHS score up to two years in paediatric SMA 2 and 3 participants and contextualise it to the Hammersmith Functional Motor Scale-Expanded (HFMSE). These change scores were considered by SMA type, motor function, and baseline RHS score. We consider a new transitional group, spanning crawlers, standers, and walkers-with-assistance, and analyse that alongside non-sitters, sitters, and walkers. The transitional group exhibit the most definitive change score trend, with an average 1-year decline of 3 points. In the weakest patients, we are most able to detect positive change in the RHS in the under-5 age group, whereas in the stronger patients, we are most able to detect decline in the RHS in the 8-13 age group. The RHS has a reduced floor effect compared to the HFMSE, although we show that the RHS should be used in conjunction with the RULM for participants scoring less than 20 points on the RHS. The timed items in the RHS have high between-participant variability, so participants with the same RHS total can be differentiated by their timed test items

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Synthesis of dispersants to generate fillers for composites designed to have an enhanced echogenic response

Ultrasound (US) imaging was identified as an advantageous imaging modality over the typically used X-ray. Thus, composites comprising of dispersed US-visible contrast agents embedded in a thermoplastic polyurethane matrix were made. To form the composite device, a commercially available material was used as a dispersant for microparticles. These coated phosphate-based glass microspheres were used as ultrasound visible contrast agents, in a medical grade polymer matrix. Ultrasound images of hollow tubes were obtained by Children’s National Medical Center (Washington DC, USA), which proved to show promising initial results. Imaging artefacts attributed to poor dispersion were observed, thus optimisation of device focussed on dispersant design. To optimise the dispersion of contrast agent throughout medical devices, bespoke dispersants were designed and synthesised to be more compatible with the matrix polymer. The first technique was to employ a thiol chain transfer agent (CTA) which was a one-pot, high yielding reaction to produce oligomers. The other method was catalytic chain transfer polymerisation (CCTP) followed by post-functionalisation of the vinyl-terminated oligomeric product via thiolene click chemistry. It was found that carboxylic acid containing thiols were excellent CTAs for monomers detailed. The synthesis of various iron-a-diimine complexes as potential alternatives to commercially available cobalt-based complexes that are typically used as control agents in catalytic chain transfer polymerisation (CCTP) was carried out. Their efficiency as chain transfer agents was investigated and related to the catalyst generation method, concentration and heating type. Although they did not exhibit high efficiencies as catalytic chain transfer agents under the conditions described, chain transfer behaviour was observed for these complexes. It was noted that molecular weight and dispersity of polymer products were lower than products obtained from uncontrolled free radical polymerisations. The differential effects of utilising microwave heating (MWH) on the rate and molecular composition of final products obtained compared to when conventionally heating (CH) was applied was also investigated. The differences were found to be related to an increase in the rate of propagation in the case of MWH conditions, which was attributed to the selective heating of particular radical species. Higher molecular weight polymers were obtained from MWH reactions, with the dispersity remaining relatively equivalent to those of the products obtained from analogous CH reactions. This suggests the selective heating of the propagating polymer radical dominated in this CCTP system rather than additional heating of the iron complex. The latter having been proposed as a potential route that electromagnetic waves may have increased the efficiencies of the iron-based catalysts due to their ferromagnetic centre in comparison to the paramagnetic cobalt complexes

Early and long term outcomes following long posterior flap vs. Skew flap for below knee amputations.

Objective To compare outcomes between long posterior flap (LPF) and skew flap (SF) amputation over a 13 year period. Methods This was a retrospective observational cohort study. Consecutive patients undergoing a LPF or SF below knee amputation (BKA) over a 13 year period at one hospital were identified. Both techniques were performed regularly, depending on tissue loss and surgeon preference. The primary outcome was surgical revision of any kind. Secondary outcomes included revision to above knee amputation (AKA), length of hospital stay (LOS), and mortality. A smaller cohort of patients who were alive and unilateral below knee amputees were contacted to ascertain prosthetic use and functional status. Results In total, 242 BKAs were performed in 212 patients (125 LPF and 117 SF; median follow up 25.8 months). Outcomes for the two groups were equivalent for surgical revision of any kind (27 LPF vs. 31 SF; p = .37), revision to an AKA (18 LPF vs. 14 SF; p = .58), LOS (29 days for LPF vs. 28 days for SF; p = .83), and median survival (23.9 months for LPF vs. 28.8 months for SF; p = .89). Multivariable analysis found amputation type had no effect on any outcome. Functional scores from a smaller cohort of 40 unilateral amputees who were contactable demonstrated improved outcomes with the LPF vs. the SF (p = .038). Conclusion Both techniques appear equivalent for rates of surgical residual limb failure. Functional outcomes may be better with the LPF