Acute upper limb infections in a regional Scottish plastic surgery unit during COVID-19: Lessons learned.

Acute upper limb infections represent a large proportion of on-call referrals and emergency theatre time in plastic surgery. To enable us to maintain effective service provision despite reallocation of hospital resources as a result of COVID-19, and to minimise patient exposure in a hospital setting during the pandemic, we introduced a walk-in clinic and dedicated local anaesthetic (LA) operating theatre for these infections. In this work, we sought to analyse our service changes and resulting patient outcomes. Using electronic records, data from patients presenting with upper extremity infections was collected before the pandemic from 1st January to 30th March 2020, then for a period of three months from 30th March until 30th June 2020, after our changes were implemented. Seventy-two patients were included before 30th March 2020, and 49 patients after. Prior to our changes, most patients underwent surgery (n = 58, 80.6%), requiring overnight admission (n = 64, 88.9%), following mainly general anaesthetic procedures (n = 56, 96.6%). After our service changes, a similar percentage of patients were treated operatively (n = 41, 83.7%), but these procedures mostly utilised LA (n = 37, 90.2%) in the outpatient setting (n = 25, 51.0%). Despite this shift in management approach, no statistically significant difference in readmission rates was calculated between the two groups (p = 0.556) and post-operative complications were fewer in absolute terms. Our results suggest that in many instances, these infections can be managed in an outpatient setting without the need for inpatient care. Selective admission with strict follow-up of patients may be feasible, improving patient experience and reducing resource burden.

Deciphering Mesenchymal Drivers of Human Dupuytren's Disease at Single-Cell Level.

Dupuytren's disease (DD) is a common, progressive fibroproliferative disease affecting the palmar fascia of the hands, causing fingers to irreversibly flex toward the palm with significant loss of function. Surgical treatments are limited; therefore, effective new therapies for DD are urgently required. To identify the key cellular and molecular pathways driving DD, we employed single-cell RNA sequencing, profiling the transcriptomes of 35,250 human single cells from DD, nonpathogenic fascia, and healthy dermis. We identify a DD-specific population of pathogenic PDPN+/FAP+ mesenchymal cells displaying an elevated expression of fibrillar collagens and profibrogenic genes. In silico trajectory analysis reveals resident fibroblasts to be the source of this pathogenic population. To resolve the processes governing DD progression, genes differentially expressed during fibroblast differentiation were identified, including upregulated TNFRSF12A and transcription factor SCX. Knockdown of SCX and blockade of TNFRSF12A inhibited the proliferation and altered the profibrotic gene expression of cultured human FAP+ mesenchymal cells, demonstrating a functional role for these genes in DD. The power of single-cell RNA sequencing is utilized to identify the major pathogenic mesenchymal subpopulations driving DD and the key molecular pathways regulating the DD-specific myofibroblast phenotype. Using this precision medicine approach, inhibition of TNFRSF12A has shown potential clinical utility in the treatment of DD.

Correlations between genomic subgroup and clinical features in a cohort of more than 3000 meningiomas.

OBJECTIVE: Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS: Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS: Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS: Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

Radiofrequency ablation for osteoid osteoma - Recurrence rates and predictive factors.

BACKGROUND AND PURPOSE: Osteoid osteoma is an infrequent but debilitating benign bone lesion which can be successfully managed by percutaneous radiofrequency ablation (RFA). There are few studies investigating the efficacy and follow-up of this treatment. An arbitrary upper limit of 15 mm has been used to differentiate between osteoid osteoma and osteoblastoma with surgery used for lesions above this limit. We aimed to analyse the cases identified from our prospectively maintained database over a ten year period since adoption of this technique in our unit. The primary objectives were to investigate factors which influenced recurrence and the time period at which patients are at risk of this. BASIC PROCEDURES: Consecutive patients with confirmed osteoid osteoma were included. Patient demographics, complications, and recurrence were recorded and multiple regression analysis was performed to investigate causation. MAIN FINDINGS: Within a minimum follow up of 21 months (mean 72), a recurrence rate of 16.3% was noted, higher than the published literature. Cox regression analysis to predict chance of recurrence revealed a relationship between larger lucent diameter and recurrence (p = 0.049, CI 95%, hazard ratio 1.33). CONCLUSIONS: The traditional cut off between osteoid osteoma and osteoblastoma appears less rigidly defined than previously thought and probably represents a progressive scale with larger lesions responding less well to RFA. This study indicates that each millimetre increase represents a ×1.33 chance of recurrence. Clinicians should counsel patients accordingly with lesions approaching the larger limits of this diagnosis.