Objective assessment of dermal fibrosis in cutaneous scarring, using optical coherence tomography, high-frequency ultrasound and immunohistomorphometry of human skin.

BACKGROUND: Noninvasive quantitative assessment of dermal fibrosis remains a challenge. Optical coherence tomography (OCT) and high-frequency ultrasound (HFUS) can accurately measure structural and physiological changes in skin. OBJECTIVES: To perform quantitative analysis of cutaneous fibrosis. METHODS: Sixty-two healthy volunteers underwent multiple sequential skin biopsies (day 0 and 1-8 weekly thereafter), with OCT and HFUS measurements at each time point supported with immunohistomorphometry analysis. RESULTS: HFUS and OCT provided quantitative measurements of skin thickness, which increased from uninjured skin (1·18 and 1·2 mm, respectively) to week 1 (1·28 mm, P = 0·01; 1·27 mm, P = 0·02), and compared favourably with haematoxylin and eosin. Spearman correlation showed good agreement between techniques (P < 0·001). HFUS intensity corresponded to dermal density, with reduction from uninjured skin (42%) to week 8 (29%) (P = 0·02). The OCT attenuation coefficient linked with collagen density and was reduced at week 8 (1·43 mm, P < 0·001). Herovici analysis showed that mature collagen levels were highest in uninjured skin (72%) compared with week 8 (42%, P = 0·04). Fibronectin was greatest at week 4 (0·72 AU) and reduced at week 8 (0·56 AU); and α-smooth muscle actin increased from uninjured skin (11·5%) to week 8 (67%, P = 0·003). CONCLUSIONS: Time-matched comparison images between haematoxylin and eosin, OCT and HFUS demonstrated that epidermal and dermal structures were better distinguished by OCT. HFUS enabled deeper visualization of the dermis including the subcutaneous tissue. Choice of device was dependent on the depth of scar type, parameters to be measured and morphological detail required in order to provide better objective quantitative indices of the quality and extent of dermal fibrosis.

Invasive pulmonary aspergillosis is associated with adverse clinical outcomes in critically ill patients receiving veno-venous extracorporeal membrane oxygenation.

To identify the incidence, risk factors and impact on long-term survival of invasive pulmonary aspergillosis (IPA) and Aspergillus colonisation in patients receiving vv-extracorporeal membrane oxygenation (ECMO). A retrospective evaluation was performed of patients receiving vv-ECMO at a tertiary hospital in Manchester (UK) between January 2012 and December 2016. Data collected included epidemiological data, microbiological cultures, radiographic findings and outcomes. Cases were classified as proven IPA, putative IPA or Aspergillus colonisation according to a validated clinical algorithm. One hundred thirty-four patients were supported with vv-ECMO, median age of 45.5 years (range 16.4-73.4). Ten (7%) patients had putative IPA and nine (7%) had Aspergillus colonisation. Half of the patients with putative IPA lacked classical host risk factors for IPA. The median number of days on ECMO prior to Aspergillus isolation was 5 days. Immunosuppression and influenza A infection were significantly associated with developing IPA in a logistic regression model. Cox regression model demonstrates a three times greater hazard of death associated with IPA. Overall 6-month mortality rate was 38%. Patients with putative IPA and colonised patients had a 6-month mortality rate of 80 and 11%, respectively. Immunosuppression and influenza A infection are independent risk factors for IPA. IPA, but not Aspergillus colonisation, is associated with high long-term mortality in patients supported with vv-ECMO.

Patient reported outcome measures in a cohort of patients at high risk of breast cancer treated by bilateral risk reducing mastectomy and breast reconstruction.

BACKGROUND: Many women with increased lifetime risk of developing breast cancer, due to pathogenic gene variants or family history, choose to undergo bilateral risk reducing mastectomies (BRRM). Patient reported outcome measures (PROMS) are an increasingly important part of informed consent but are little studied in women undergoing BRRM. METHODS: We used a validated PROMS tool for breast reconstruction (BREAST-Q) in 297 women who had BRRM and breast reconstruction, 81% of whom had no malignancy (Benign Group, BG) and 19% in whom a perioperative breast cancer was diagnosed (Cancer Group, CG). 128 women also completed a Hospital Anxiety & Depression Score (HADS) questionnaire to test if preoperative HADS score could predict PROMS outcomes. RESULTS: Women in the CG had lower PROMS scores for satisfaction with their breasts, nipple reconstruction and sexual wellbeing. Both groups reported equal satisfaction with BRRM outcome and psychosocial well-being. Physical well-being PROMS of the abdomen and chest were high in women in both groups as were scores for satisfaction with the care they received. The CG group reported suboptimal quality of patient information. A higher presurgical HADS anxiety score predicted less favourable postoperative psychosocial well-being despite similar levels of satisfaction with aesthetic outcome. CONCLUSION: We show a high degree of patient reported satisfaction by woman undergoing BRRM and reconstruction. There was a negative association with a cancer diagnosis on quality of life PROMS and higher preoperative anxiety levels negatively affected postoperative psychosocial well-being. These important findings should be part of the informed consent process during preoperative counselling.

A prospective cohort study on the safety of checkpoint inhibitors in older cancer patients - the ELDERS study.

OBJECTIVE: Older cancer patients are underrepresented in the pivotal trials of checkpoint inhibitors (CPIs). This study aimed to investigate the impact of an ageing immune system on CPI-related toxicity and provide evidence for the role of geriatric assessments with CPI. METHODS: The ELDERS study is a prospective observational study with two cohorts: older (70+ years of age) and younger (<70 years of age). Patients with advanced/metastatic non-small-cell lung cancer or melanoma starting single-agent CPI were eligible. The older cohort was assessed for frailty with Geriatric-8 (G8) screening, which when positive (<15 points) was followed by a holistic set of geriatric assessments. Primary endpoint was the incidence of grade 3-5 immune-related adverse events (irAEs). RESULTS: One hundred and forty patients were enrolled with 43% being pretreated and pembrolizumab represented 92% of treatments on study. The older cohort had a significantly higher comorbidity burden (P < 0.001) and polypharmacy (P = 0.004). While 50% of older patients had a positive G8 screening, 60% on this frail subgroup had a performance status score of 0 or 1. There was no significant difference in the incidence of irAEs grade 3-5 between older and younger cohorts (18.6% versus 12.9%; odds ratio 1.55, confidence interval 95% 0.61-3.89; P = 0.353). Exposure to systemic steroids due to irAEs was numerically longer for older patients (22 versus 8 weeks; P = 0.208). A positive G8 screening predicted hospital admissions (P = 0.031) and risk of death (P = 0.01). CONCLUSIONS: The use of CPI in older patients was not associated with more high-grade toxicity. The G8 screening identified a subgroup with higher risk of AEs and its implementation should be considered in the context of CPI.

A Predictive Model for Reactive Tube Feeding in Head and Neck Cancer Patients Undergoing Definitive (Chemo) Radiotherapy.

AIMS: Careful management of a patient's nutritional status during and after treatment for head and neck squamous cell cancers (HNSCC) is crucial for optimal outcomes. The aim of this study was to develop a model for stratifying a patient's risk of requiring reactive enteral feeding through a nasogastric tube during radiotherapy for HNSCC, based on clinical and treatment-related factors. MATERIALS AND METHODS: A cohort of consecutive patients treated with definitive (chemo)radiotherapy for HNSCC between January 2016 and January 2018 was identified in the institutional electronic database for retrospective analysis. Patients requiring enteral feeding pretreatment were excluded. Clinical and treatment data were obtained from prospectively recorded electronic clinical notes and planning software. RESULTS: Baseline patient characteristics and tumour-related parameters were captured for 225 patients. Based on the results of the univariate analysis and using a stepwise backwards selection process, clinical and dosimetric variables were selected to optimise a clinically predictive multivariate model, fitted using logistic regression. The parameters found to affect the probability, P, of requiring a nasogastric feeding tube for >4 weeks in our clinical multivariate model were: tumour site, tumour stage (early T0/1/2 stage versus advanced T3/T4 stage), chemotherapy drug (none versus any drug) and mean dose to the contralateral parotid gland. A scoring model using the regression coefficients of the selected variables in the clinical multivariate model achieved an area under the curve (AUC) of 0.745 (95% confidence interval 0.678-0.812), indicating good discriminative performance. Internal validation of the model involved splitting the dataset 80:20 into training and test datasets 10 times and assessing differences in AUC of the model fitted to these. CONCLUSIONS: We developed an easy-to-use prediction model based on both clinical and dosimetric parameters, which, once externally validated, can lead to more personalised treatment planning and inform clinical decision-making on the appropriateness of prophylactic versus reactive enteral feeding.

Does laminar flow reduce the risk of early surgical site infection in hip fracture patients?

OBJECTIVE: To determine if there is a difference in the rate of early infection in hip fracture surgery performed under laminar flow and conventional turbulent ventilation. METHOD: The impact on the rates of early surgical site infection (SSI) in patients who sustained a hip fracture after our trauma theatre was moved from a laminar to a non-laminar flow theatre was assessed. Data was retrospectively collected for six months prior to the merging of the trauma service and six months after. For each operation: age, gender, American Society of Anesthesiologists (ASA) grade, dementia, diabetes, immunosuppressants, anticoagulation, smoking status, duration of surgery, administration of peri-operative antibiotics, surgeon grade, skin closure method, and SSI were extracted from the hospital electronic notes with input from the trust's SSI surveillance team. RESULTS: 259 hip fracture operations were performed during this period. Seven patients were excluded due to incomplete information. There were 95 patients in the laminar flow group and 157 in the non-laminar flow group. There were no SSIs in the laminar flow group and a 3.2% SSI rate (Fishers exact p = 0.16) in the non-laminar flow group. Three were superficial infections and two deep. This difference was not statistically significant. Patient characteristics were included in a Firth logistic regression model which did not show a significant change in the odds ratio. CONCLUSION: A higher incidence of early SSI was found when hip fracture surgery was performed under non-laminar flow conditions but this difference was not statistically significant. Larger studies may change this outcome.

An analysis of the cosmetic surgery experience acquired through UK plastic surgery training.

AIMS: Cosmetic surgery is an essential component of Plastic Surgery training. Our study demonstrates the average cosmetic surgery experience of UK Plastic Surgery registrars over their 6-year training scheme. Comparison is made with the operative requirements for the Certificate of Completion of Training (CCT) and the Royal College of Surgeons (RCS) Cosmetic Certification scheme. METHODS: By using the web-based eLogbook, we analysed all the cosmetic surgery operations recorded by Plastic Surgery registrars during their specialist training. The weighted mean average number of procedures was calculated for different areas of cosmetic surgery practice, according to the level of supervision. The number of RCS cosmetic credits acquired for eight domains of cosmetic surgery was calculated, thus enabling comparison with the operative requirements for certification. RESULTS: eLogbook data were collated for 454 registrars from 2010 to 2016 inclusive. Trainees participated in a mean of 122 cosmetic operations during their training (50% as an assistant), which satisfies the requirement of 100 procedures for CCT. The majority of trainee involvement (66%) was with cosmetic breast and body contouring cases. Comparison with the criteria for cosmetic certification reveals that on average, trainees could certify in cosmetic breast and body contouring surgery but would be unable to accredit in other areas of practice. CONCLUSIONS: Current UK training affords sufficient cosmetic surgery exposure for CCT but offers a limited breadth of exposure. Trainees who wish to certify in cosmetic surgery of the head and neck region will likely be required to seek additional experience outside their deanery training programme.

Chronic pulmonary aspergillosis as a cause of smear-negative TB and/or TB treatment failure in Nigerians.

OBJECTIVE: To evaluate chronic pulmonary aspergillosis (CPA) as an alternative diagnosis of smear-negative tuberculosis (TB) and treatment failure in TB patients in Nigeria. METHODS: We conducted a cross-sectional multicentre survey in human immunodeficiency virus (HIV) positive and negative adult patients at the end of their TB treatment in clinics in Lagos and Ilorin states. All were assessed using clinical examination, chest X-ray (CXR) and aspergillus immunoglobulin G (IgG) serology, and some for sputum fungal culture. CPA was defined as a positive Aspergillus fumigatus IgG titre with compatible CXR or a positive sputum culture of Aspergillus with a visible fungal ball on CXR with symptoms of underlying lung disease. RESULTS: Of 208 patients recruited between June 2014 and May 2015, 153 (73.6%) were HIV-positive. The mean age was 39.8 years, 124 (59.6%) were female and 39 (18.8%) were unable to work. The median CD4 count was 169.5 cells/ml (range 4-593) in HIV-infected patients with positive Aspergillus IgG. Overall, 109 (52.4%) had documented TB, 140 (67.3%) had a productive cough and 50 had haemoptysis. CPA prevalence was 8.7%; 10 (6.5%) had HIV infection and 8 (14.5%) were HIV-negative (Fisher's exact P = 0.092). CONCLUSION: CPA is a neglected disease in Nigeria, and most cases match the World Health Organization diagnostic criteria for smear-negative TB.

The Burden of Cognitive Impairment in Patients With End-Stage Renal Disease and Impact on Dialysis Modality Choice.

INTRODUCTION: Kidney disease is associated with significant cognitive dysfunction. Subjective reports of cognitive ability have not been studied extensively in chronic kidney disease. We investigated the association between objective and subjective cognitive functions in predialysis patients and their association with self-care dialysis modality choice. METHODS: Cross-sectional data from the Barriers to Successful Implementation of Care in Home Haemodialysis study were used for the study of cognition in 220 predialysis patients. The data were used to ascertain the demographics, clinical, laboratory, and neuropsychometric variables. The latter includes Trail Making Tests (TMT) parts A and B, Modified Mini Mental State Examination, and metacognition questionnaire for subjective assessment of one's cognitive ability. The outcome variable was fully assisted and self-care dialysis modality choice. RESULTS: Within the study cohort, 90 patients chose fully assisted hemodialysis and 114 patients chose self-care dialysis. The median Modified Mini Mental State Examination, TMT part A, and TMT part B scores were greater for the assisted versus the self-care group. Metamemory was not significantly different between groups, but the metaconcentration score was significantly worse in the group choosing assisted dialysis. Higher (i.e., better) metaconcentration scores were significantly associated with the self-care modality choice in the univariate and hierarchical regression analyses. Adjusted and unadjusted analyses showed a significant association between perceived concentration and TMT part B scores (P < 0.01). With every 1.6-minute increase in TMT part B score, there was a 1-unit reduction in metaconcentration score, and the latter was associated with 20% lower odds of choosing self-care dialysis over a fully assisted dialysis modality. DISCUSSION: Patients' self-perception of cognitive ability is a significant predictor of self-care dialysis modality choice. Subjective report of "metaconcentration" is also strongly associated with poorer outcome on the TMT part B.

Acute medicine targets: when should the clock start and 7-day consultant impact?

BACKGROUND: Early consultant review has been shown to improve outcomes in patients presenting to the Acute Medical Unit (AMU). The Society for Acute Medicine (SAM) clinical quality indicators use the time of arrival on the AMU for target rather than arrival in the Emergency Department (ED) although this is where most acute medical patients present. AIM: To determine the effect of a 7-day Consultant Acute Physician model on patient waiting times and assess the impact of starting the clock for medical patients at time of ED arrival. DESIGN: We performed an audit at a University Hospital AMU in the North West of England. METHODS: Data were collected prospectively for 15 consecutive days in May-June 2013 for all patients presenting to the AMU at University Hospital of South Manchester and were repeated for the same time period in 2014 following the introduction of a new Consultant working model. RESULTS: Four hundred and five patients were admitted to the AMU in the 2013 cohort compared to 456 in the 2014 cohort. There was a significant improvement in the median waiting time for Consultant review from AMU admission to 5 h 53 min from 8 h 15 min (P < 0.001). The compliance with the SAM quality indicator for Consultant review improved from 88.7 to 93.7% (P = 0.022). CONCLUSION: A 7-day Acute Physician working model is improving performance with regards to patient waiting times. We suggest that starting the clock for acute medical patients in the ED is a better measure of performance than on arrival to the AMU.