Patient-initiated follow-up for high-risk cutaneous squamous cell carcinoma. How we do it and two years of outcome data.

Why do we follow-up patients with high-risk cutaneous squamous-cell carcinomas (cSCC)? Current guidance suggests we offer post-treatment follow-up appointments at regular intervals for 24 months. Is this to improve prognosis, provide psychological support or find the next cancer? Recent data confirms recurrence and metastasis to be rarer events. We question whether these follow-up practices are truly 'needed' by introducing an option of patient-initiated follow-up (PIFU). We enrolled 476 cSCC patients (January 2020 - January 2023) who fulfilled the definition of high-risk cSCC based on guidelines in use at the time. 59 patients were excluded. 53% (n=250) did not re-contact us during the 2-year period, with no clinical record of complications or recurrences. 35% (n=167) utilised the PIFU pathway, of which 119 patients only required 1 face-to-face appointment. 7 patients (1.5%) developed metastatic disease, 11 patients developed recurrence, and 68 patients developed cSCC at another site. All lesions were identified by the patient via PIFU. We saved 1250 follow-up appointments from those that did not contact us (n=250); financially equating to £181,462.50. Our data implies that PIFU can be considered safe alternative practice for patients with cSCC. Patients independently identified the need for review without scheduled follow-up, making these appointments available to other patient cohorts. Although follow-up appointments may provide mental health support, they can be inconvenient and not the ideal use of our health resources. Our findings support a call for revision of existing skin cancer health policies, to cope with and subsequently improve our practices, to better patient care.

Patient-led teledermatology for skin lesion triage: a service evaluation of the DyplensTM dermoscope.

Despite the huge improvement in smartphone cameras, there has not been any real interest in the UK in pursuing patient-facing teledermatology within the sphere of skin lesion triage. High-specification dermoscopic images can be generated with smartphone attachments, but, to date, no formal clinical trial has been performed to establish the efficacy and feasibility of these consumer-level dermoscopes in skin lesion triage. The objectives of this study were to assess the ability of patients to capture dermoscopic images using a smartphone attachment, and to identify the safety and diagnostic accuracy of consumer-level dermoscopy in triaging out benign skin lesions from the 2-week-wait (2WW) cancer pathway. We recruited 78 patients already attending a face-to-face clinic at two locations. They were provided with instruction leaflets and asked to obtain dermoscopic and macroscopic images of their lesion(s) using their own smartphones. The images (and a brief history) were distributed to five experienced blinded assessors (consultants), who were asked to state their working diagnosis and outcome (reassurance, routine review or 2WW pathway), as they would in teledermatology. We compared their outcomes to the gold-standard in-person diagnosis and/or histological diagnosis, where available. The device achieved 100% sensitivity in diagnosing melanoma and squamous cell carcinoma (SCC). The specificity for the diagnoses of melanoma (89%) and SCC (83%) was high. The overall diagnostic accuracy was 77% for both benign and malignant lesions, The diagnostic accuracy was high for seborrhoeic keratosis (91%) and simple naevi (81%). Patient-captured dermoscopic images using bespoke smartphone attachments could be the future in safely triaging out benign lesions.

Antifungal activity of eumelanin-inspired indoylenepheyleneethynylene against Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic fungal pathogen that causes meningitis in >152,000 immunocompromised individuals annually, leading to 112,000 yearly deaths. The four classes of existing antifungal agents target plasma membrane sterols (ergosterol), nucleic acid synthesis, and cell wall synthesis. Existing drugs are not highly effective against Cryptococcus, and antifungal drug resistance is an increasing problem. A novel antimicrobial compound, a eumelanin-inspired indoylenepheyleneethynylene, EIPE-1, was synthesized and has antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MSRA), but not towards Gram-negative organisms. Based on EIPE-1's antibacterial activity, we hypothesized that EIPE-1 could have antifungal activity. For these studies, we tested EIPE-1 against C. neoformans strain H99 and 6 additional cryptococcal clinical isolates. We examined antifungal activity, cytotoxicity, effects on fungal gene expression, and mechanism of action of EIPE-1. Results showed that EIPE-1 has fungicidal effects on seven cryptococcal strains with MICs ranging from 1.56 to 3.125 µg/mL depending on the strain, and it is non-toxic to mammalian cells. We conducted scanning and transmission electron microscopy on the exposed cells to examine structural changes to the organism following EIPE-1 treatment. Cells exposed displayed structural changes to their cell wall and membranes, with internal contents leaking out of the cells. To understand the effect of EIPE-1 on fungal gene expression, RNA sequencing was conducted. Results showed that EIPE-1 affects several processes involved stress response, ergosterol biosynthesis, capsule biosynthesis, and cell wall attachment and remodeling. Therefore, our studies demonstrate that EIPE-1 has antifungal activity against C. neoformans, which affects both cellular structure and gene expression of multiple fungal pathways involved in cell membrane stability and viability.

Valsalva Maneuver to Identify Dermal Bleeders after Paramedian Flap Elevation Under Local Anesthesia.

The paramedian forehead flap (PFF) provides a reliable reconstruction option for complex nasal tip defects. The robust blood supply from a well perfused pedicle allows for reconstruction of large defects of the nasal tip for which simpler methods/techniques would provide inadequate coverage or result in inferior cosmesis. A well-designed PFF containing the supratrochlear artery inherently predisposes to small vessel bleeding from the pedicles cut edge. Due to the well perfused nature of the pedicle, there is an increased risk of post-operative bleeding. We describe a technique for better identifying bleeding points from the pedicle to optimise intra-operative haemostasis by performing the Valsalva maneuver using a syringe intraoperatively.

A multinational survey characterizing the use of surgical magnifying loupes in dermatological surgery.

BACKGROUND: The use of surgical loupes has not been well-documented in dermatological surgery. OBJECTIVES: An online questionnaire was developed to characterize the use of loupes in dermatological surgery. METHODS: The questionnaire was circulated to the memberships of the British Society of Dermatological Surgery, the European Society of Micrographic Surgery, and the Australasian College of Dermatologists. Responses were analyzed with a mixed methods approach using quantitative data analysis and inductive content analysis. RESULTS: One-hundred twenty-five valid responses were received from 20 nations. Most respondents were from England (40%; 50/125), Australia (16%; 20/125), and the Netherlands (14.4%; 18/125). Overall, 71.2% (89/125) of respondents were consultants/Facharzt/attending. Furthermore, 55.2% (69/125) of respondents were Mohs surgeons. In dermatological surgery 38.4% (48/125) of respondents used surgical loupes routinely. The mode magnification level for loupes was 2.5× (67.5%; 27/40), with 3× second place (12.5%; 5/40). Exactly half (20/40) used through-the-lens style loupes and 40% (16/40) used flip-up-loupes. Inductive content analysis of the 51 free-text responses from nonloupe users uncovered several deterring factor themes, including expense (18/51), can manage without/don't need (14/51), and narrow field of view a(11/51), and uncomfortable/too heavy (9/51). CONCLUSIONS: This is the first time the use of surgical loupes in dermatological surgery has been internationally characterized.

An international survey characterizing Mohs tissue processing techniques and Mohs margin thresholds: how close is too close?

BACKGROUND: From practice, we identified heterogeneity in Mohs micrographic surgery (MMS) specimen tissue processing techniques and specifications, and in the Mohs surgeons' assessment of MMS specimen histological tumour clearance. AIM: By surveying an international cohort of Mohs surgeons, we determined to characterize variation in margin threshold assessment (number of wafers/sections free of tumour to declare tumour clearance). METHODS: An online questionnaire was distributed to Mohs surgeons in the UK, European countries, Australia and New Zealand, assessing the background demographics of the surgeons and the technical factors involved in MMS tissue processing and posing three MMS scenarios to define margin thresholds. RESULTS: In total, 114 consultant/attending-level Mohs surgeons responded, giving a response rate of 33.5% from 20 countries (including UK nations). The first scenario posed was a 20-mm cheek basal cell carcinoma (BCC) excised by MMS with a fully complete first wafer (7 µm) clear of tumour and the second wafer (after trimming interval of 50 µm) demonstrating a small dermal focus of nodular BCC; of the 58 surgeons, 16 (27.6%) would not take another stage. With a follow-up question, 16 of the 58 (27.6%) surgeons specified wanting three clear sections to declare tumour clearance. When the same scenario had a change to a 20-mm infiltrative BCC, 84.2% (48 of 57 surgeons) required a second MMS stage, with a follow-up question clarifying that a third (19 of 57) wanted three clear sections to determine clearance. For a well-differentiated 15-mm squamous cell carcinoma with the same factors there was no majority consensus, with the same proportion of surgeons (22.6%; 12 of 53) calling tumour clearance after one, two and three clear section(s) respectively. For MMS specimen processing specifications, routine sections/wafers of 5-10 µm were reported by 77.4% of respondents (48 of 62) and for trimming interval values, 78.6% (48 of 61) specified a range between 20 and 200 µm. CONCLUSION: By surveying international Mohs surgeons, we highlight surgeon background characteristics, peer-compare assessment of margin thresholds for tumour clearance across three scenarios, and delineate tissue processing and intraoperative approaches.

Eumelanin-Inspired Antimicrobial with Biocidal Activity against Methicillin-Resistant Staphylococcus aureus.

The reliance on antibiotics and antimicrobials to treat bacterial infectious diseases is threatened by the emergence of antibiotic resistance and multi-drug-resistant organisms, thus having the potential to greatly impact human health. Thus, the discovery and development of antimicrobials capable of acting on antibiotic-resistant bacteria is a major area of significance in scientific research. Herein, we present the development of a eumelanin-inspired antimicrobial capable of killing methicillin-resistant Staphylococcus aureus (MRSA). By ligating quaternary ammonium-functionalized "arms" to a eumelanin-inspired indole with intrinsic antimicrobial activity, an antimicrobial agent with enhanced activity was prepared. This resulting antimicrobial, EIPE-1, had a minimum inhibitory concentration of 16 µg/mL (17.1 µM) against a clinical isolate of MRSA obtained from an adult cystic fibrosis patient. The biocidal activity occurred within 30 min of exposure and resulted in changes to the bacterial cell surface as visualized with a scanning electron microscope. Taken together, these studies demonstrate that EIPE-1 is effective at killing MRSA.

Development and Characterization of Novel Conductive Sensing Fibers for In Vivo Nerve Stimulation.

Advancements in electrode technologies to both stimulate and record the central nervous system's electrical activities are enabling significant improvements in both the understanding and treatment of different neurological diseases. However, the current neural recording and stimulating electrodes are metallic, requiring invasive and damaging methods to interface with neural tissue. These electrodes may also degrade, resulting in additional invasive procedures. Furthermore, metal electrodes may cause nerve damage due to their inherent rigidity. This paper demonstrates that novel electrically conductive organic fibers (ECFs) can be used for direct nerve stimulation. The ECFs were prepared using a standard polyester material as the structural base, with a carbon nanotube ink applied to the surface as the electrical conductor. We report on three experiments: the first one to characterize the conductive properties of the ECFs; the second one to investigate the fiber cytotoxic properties in vitro; and the third one to demonstrate the utility of the ECF for direct nerve stimulation in an in vivo rodent model.

Covalently Loaded Naloxone Nanoparticles as a Long-Acting Medical Countermeasure to Opioid Poisoning.

The mu opioid receptor antagonist naloxone has been a vital, long-standing countermeasure in the ongoing battle against opioid use disorders (OUD) and toxicity. However, due to its distinctive short elimination half-life, naloxone has shown diminished efficacy in cases of synthetic opioid poisoning as larger or repeated doses of the antidote have been required to achieve adequate reversal of severe respiratory depression and prevent episodes of renarcotization. This report describes the synthesis, characterization, and in vivo evaluation of a novel, nanoparticle-based naloxone formulation that provides extended protection against the toxic effects of the powerful synthetic opioid fentanyl. The strategy was predicated on a modified two-step protocol involving the synthesis and subsequent nanoprecipitation of a poly(lactic-co-glycolic acid) polymer scaffold bearing a covalently linked naloxone chain end (drug loading ∼7% w/w). Pharmacokinetic evaluation of the resulting covalently loaded naloxone nanoparticles (cNLX-NP) revealed an elimination half-life that was 34 times longer than high dose free naloxone (10 mg/kg) in male Sprague-Dawley rats. This enhancement was further demonstrated by cNLX-NP in subsequent in vivo studies affording protection against fentanyl-induced respiratory depression and antinociception for up to 48 h following a single intramuscular injection. These discoveries support further investigation of cNLX-NP as a potential therapeutic to reverse overdose and prevent renarcotization from fentanyl and its potent analogs.

Predictors of Severe COVID-19 in Patients With Diabetes: A Multicenter Review.

OBJECTIVE: Diabetes is an independent risk factor for severe SARS-CoV-2 infections. This study aims to elucidate the risk factors predictive of more severe outcomes in patients with diabetes by comparing the clinical characteristics of those requiring inpatient admissions with those who remain outpatient. METHODS: A retrospective review identified 832 patients-631 inpatients and 201 outpatients-with diabetes and a positive SARS-CoV-2 test result between March 1 and June 15, 2020. Comparisons between the outpatient and inpatient cohorts were conducted to identify risk factors associated with severity of disease determined by admission rate and mortality. Previous dipeptidyl peptidase 4 inhibitor use and disease outcomes were analyzed. RESULTS: Risk factors for increased admission included older age (odds ratio [OR], 1.04 [95% CI, 1.01-1.06]; P = .003), the presence of chronic kidney disease (OR, 2.32 [1.26-4.28]; P = .007), and a higher hemoglobin A1c at the time of admission (OR, 1.25 [1.12-1.39]; P < .001). Lower admission rates were seen in those with commercial insurance. Increased mortality was seen in individuals with older age (OR, 1.09 [1.07-1.11]; P < .001), higher body mass index number (OR, 1.04 [1.01-1.07]; P = .003), and higher hemoglobin A1c value at the time of diagnosis of COVID-19 (OR, 1.12 [1.01-1.24]; P = .028) and patients requiring hospitalization. Lower mortality was seen in those with hyperlipidemia. Dipeptidyl peptidase 4 inhibitor use prior to COVID-19 infection was not associated with a decreased hospitalization rate. CONCLUSION: This retrospective review offers the first analysis of outpatient predictors for admission rate and mortality of COVID-19 in patients with diabetes.

"Benchtop" Biaryl Coupling Using Pd/Cu Cocatalysis: Application to the Synthesis of Conjugated Polymers.

Typically, Suzuki couplings used in polymerizations are performed at raised temperatures in inert atmospheres. As a result, the synthesis of aromatic materials that utilize this chemistry often demands expensive and specialized equipment on an industrial scale. Herein, we describe a bimetallic methodology that exploits the distinct reactivities of palladium and copper to perform high yielding aryl-aryl dimerizations and polymerizations that can be performed on a benchtop under ambient conditions. These couplings are facile and can be performed by simple mixing in the open vessel. To demonstrate the utility of this method in the context of polymer synthesis: polyfluorene, polycarbazole, polysilafluorene, and poly(6,12-dihydro-dithienoindacenodithiophene) were created at ambient temperature and open to air.

A Diverse View of Science to Catalyse Change.

Valuing diversity leads to scientific excellence, the progress of science and most importantly, it is simply the right thing to do. We can value diversity not only in words, but also in actions.