Adaptive self‐organization in the embryo: its importance to adult anatomy and to tissue engineering

The anatomy of healthy humans shows much minor variation, and twin‐studies reveal at least some of this variation cannot be explained genetically. A plausible explanation is that fine‐scale anatomy is not specified directly in a genetic programme, but emerges from self‐organizing behaviours of cells that, for example, place a new capillary where it happens to be needed to prevent local hypoxia. Self‐organizing behaviour can be identified by manipulating growing tissues (e.g. putting them under a spatial constraint) and observing an adaptive change that conserves the character of the normal tissue while altering its precise anatomy. Self‐organization can be practically useful in tissue engineering but it is limited; generally, it is good for producing realistic small‐scale anatomy but large‐scale features will be missing. This is because self‐organizing organoids miss critical symmetry‐breaking influences present in the embryo: simulating these artificially, for example, with local signal sources, makes anatomy realistic even at large scales. A growing understanding of the mechanisms of self‐organization is now allowing synthetic biologists to take their first tentative steps towards constructing artificial multicellular systems that spontaneously organize themselves into patterns, which may soon be extended into three‐dimensional shapes.     

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes

IntroductionDissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales.MethodsA 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications.ResultsA total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively.ConclusionsFunnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.     

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Prioritizing core components of successful transitions from child to adult mental health care: a national Delphi survey with youth,caregivers, and health professionals

Youth accessing mental health care often experience a disruption in care as they attempt to transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS). Few studies have evaluated interventions seeking to improve the experience and outcomes of CAMHS–AMHS transitions, in part due to lack of consensus on what constitutes best practices in intervention success. As such, the aim of this study was to engage patients, caregivers, and clinicians to prioritize core components of successful CAMHS–AMHS transitions which can be used in the design or evaluation of transition interventions. As such, a Delphi study was conducted to determine core components of successful CAMHS–AMHS transitions. Guided by the principles of patient-oriented research, three balanced expert panels consisting of youth, caregivers, and clinicians ranked and provided feedback on the importance and feasibility of core components of CAMHS-AMHS transitions. Components endorsed as feasible or important with ≥ 70% agreement from any panel moved to the next round. As a result, a list of 26 core components of CAMHS–AMHS transitions has been refined which can be used in the design, implementation, or evaluation of interventions intended to improve transition experiences and outcomes for youth in mental health care. Youth and families were engaged in an expert advisory role throughout the research process, contributing their important perspectives to the design and implementation of this study, as well as interpretation of the findings.

     

Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics

Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV_1-2 (mild-moderate CAV), CAV₃ (severe CAV), and CAV₀ (normal control). SOMAscan assays were performed and proteins quantitated. Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV. These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies.     

MRI-Based Shoulder Osteoarthritis Severity score (SOAS) is predictive of functional improvement following total shoulder arthroplasty

BackgroundTotal shoulder arthroplasty (TSA) is an increasingly common treatment for end-stage glenohumeral osteoarthritis. Current established radiographic measures and classification systems do not predict patient-reported outcomes from TSA. We hypothesized that the MRI-based Shoulder Osteoarthritis Severity (SOAS) Score would correlate with subjective improvement following TSA.MethodsPatients undergoing TSA with preoperative shoulder MRIs and pre- and postoperative ASES scores with minimum 2-year follow-up were included from a prospectively collected institutional shoulder arthroplasty database. SOAS scores, which is measured from 0 to 100 with an increasing score reflecting greater global degenerative changes, were assessed by two independent reviewers, and Samilson-Prieto grade and Walch classification were scored by one reviewer. Average SOAS scores were correlated with demographic factors and pre-, post-, and change (Δ) in ASES scores. Statistical analysis was performed with STATA with Pearson's correlation, one-way ANOVA, and ROC analysis, with significance defined by p <.05.Results30 patients (age 63 ± 10 years, 14 females, 16 males) who underwent primary anatomic TSA were included. The intraclass correlation coefficient (ICC) for total SOAS scores calculated by reviewers was 0.91. SOAS score correlated significantly with ΔASES (r = 0.61, p = .0003) and preoperative ASES (r = -0.37, p = .042), with greater MRI-based degenerative change associated with greater improvement after TSA and lower preoperative ASES score. No significant relationship was found between either Samilson-Prieto or Walch classification and SOAS or ASES scores. No significant relationship was found between SOAS scores and age, sex, or BMI. Using an MCID of 21 as previously reported, an ROC curve was generated and found to have an AUC of 0.96. A SOAS score cut-point of 36.25 was found to maximize sensitivity and specificity in predicting reaching MCID.ConclusionWe observed a significant positive correlation between the MRI-based SOAS score and functional improvement following TSA measured using change in ASES scores, indicating that patients with more advanced degenerative changes on MRI had greater improvement after shoulder replacement surgery. We found that the correlation strength was highest when comparing total SOAS score to ΔASES as opposed to any individual sub-component of the SOAS score. The MRI-based SOAS score for shoulder osteoarthritis may be a valuable tool for predicting patient outcomes following TSA.Level of evidenceLevel III; Retrospective Cohort Comparison; Prognosis Study