The Development and Feasibility of a Novel Electronic Patient-Reported Outcome Measures (Eproms) Questionnaire in patients with penile cancer.

BACKGROUND: Penile cancer (PeCa) is a rare cancer with surgical options that affect patients' quality-of-life. Patient-reported outcome measures (PROMs) are uncommonly utilized in this cohort despite their several patient-centered benefits and there are recommendations to further digitalize PROMs. This prospective, population-based study aimed to report the development and feasibility of a novel electronic patient-reported outcome measures (ePROMs) questionnaire for patients with PeCa. MATERIALS AND METHODS: A novel ePROMs questionnaire was developed and sent to patients 3 days before outpatient clinic appointments. The questionnaire included up to 30 items on patient symptomology and quality-of-life, including a self-reported quality-of-life score (rated 0 being worst and 100 being best). Data were collected for patients followed up between August 2021 and May 2022. The primary feasibility outcomes, adherence and engagement, were measured by response and drop-out rates. Differences in responders and nonresponders were also ascertained. Secondary outcomes explored the clinical utility of the questionnaire. Responders were subcategorized into 3 groups: circumcision (Ci), partial penectomy (PP) or total penectomy (TP) and differences were analyzed. This study was approved by the local Trust Governance Panel, including for ethical considerations. RESULTS: 220 adult males were sent ePROMs questionnaires, and 141 (64%) responded initially. The mean dropout rate of subsequent questionnaires was 56%. The maximum number of questionnaires sent to and completed by a patient was 8 (n = 1). Nonresponders were older (P < .0001), with poorer performance status (P < .0001) and lower body mass index (P = .0288). TP patients reported the lowest median quality-of-life score 68.50 (8-99), followed by the Ci group (72.0, 37-94) and the PP group (76.0, 10-99). CONCLUSIONS: Patients initially engaged and adhered to the ePROMs questionnaire but struggled to maintain this over time. Clinical data gathered by the questionnaire may be utilized to inform patient care. The questionnaire requires additional validation, research, and education.

Minimal scarring in a premature neonate.

Background: Scar formation and management is one of the major issues in plastic surgery. Scars are a chronic burden to patients, their families, and the wider healthcare system and while non-surgical and surgical options have been shown to reduce scarring and its impact, there are currently no therapeutic options to completely heal scars or to avoid scarring. Early gestation animals have been reported to heal skin wounds without scarring. Case presentation: We report on a premature, underweight-for-age neonate of 30 weeks' gestation that suffered a combination of deep partial thickness abrasions and full thickness wounds following birth trauma, who eventually healed with minimal skin scarring. Conclusion: This case highlights that more research is needed to understand the mechanism and timelines of foetal skin healing, so the knowledge can be used to develop better therapeutic options to treat skin scars in adults.

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas. Excessive extracellular matrix deposition (fibrosis) is the key driver of chronic disease progression. However, little attention was paid to the impact of disrupted circadian rhythm in hepatic stellate cells (HSCs) which are the primary mediator of fibrotic ECM deposition. Here, we showed in vitro and in vivo that liver fibrosis is significantly increased when circadian rhythm is disrupted by CLOCK mutation. Quiescent HSCs from CLOCKΔ19 mice showed higher expression of RhoGDI pathway components and accelerated activation. Genes altered in this primed CLOCKΔ19 qHSC state may provide biomarkers for early liver disease detection, and include AOC3, which correlated with disease severity in patient serum samples. Integration of CLOCKΔ19 microarray data with ATAC-seq data from WT qHSCs suggested a potential CLOCK regulome promoting a quiescent state and downregulating genes involved in cell projection assembly. CLOCKΔ19 mice showed higher baseline COL1 deposition and significantly worse fibrotic injury after CCl4 treatment. Our data demonstrate that disruption to circadian rhythm primes HSCs towards an accelerated fibrotic response which worsens liver disease.