Validation of a microRNA liquid biopsy assay for diagnosis and risk stratification of invasive cutaneous melanoma.

BACKGROUND: Noninvasive molecular biomarkers are needed to improve the early, accurate and precise diagnosis of invasive cutaneous melanoma. OBJECTIVES: To independently validate a previously identified circulating microRNA signature of melanoma (MEL38), and, secondly, to develop a complementary microRNA signature, optimized for prognostication. PATIENTS AND METHODS: MicroRNA expression profiling was performed on plasma samples from a multicentre observational case-control study, involving patients with primary or metastatic melanoma, melanoma in situ, nonmelanoma skin cancer, or benign naevi. MicroRNA profiles from patients with length of survival, treatment and sentinel lymph node biopsy (SLNB) data were used to develop the prognostic signature. The primary outcome of interest for MEL38 was its association with melanoma status, including area under the curve, binary diagnostic sensitivity and specificity, and incidence-adjusted positive and negative predictive values. The prognostic signature was assessed using rates of survival per risk group and relationship to conventional predictors of outcome. RESULTS: Circulating microRNA profiles of 372 patients with invasive melanoma and 210 control individuals were generated. The average age of all participants was 59 years; 49% were male. A MEL38 score > 5.5 indicated the presence of invasive melanoma. Overall, 551/582 (95%) of patients were correctly diagnosed, with 93% sensitivity and 98% specificity. MEL38 score ranged from 0 to 10 with an area under the curve of 0.98 (95% confidence interval 0.97-0.99, P < 0.001). A novel prognostic 12-microRNA signature (MEL12) developed from 232 patients identified low-, standard- or high-risk groups, with 94%, 78% and 58% rates of 10-year melanoma-specific survival, respectively (log-rank P < 0.001). MEL12 prognostic risk groups were significantly associated with clinical staging (χ2, P < 0.001) and SLNB status (P = 0.027). Patients who were classified as high risk by MEL12 were approximately three times more likely to have melanoma detected in their sentinel lymph nodes compared to low-risk patients. CONCLUSIONS: The circulating MEL38 signature may assist in diagnosing patients with invasive melanoma vs. other conditions associated with a lower - or negligible - risk of mortality. A complementary and prognostic MEL12 signature is predictive of SLNB status, clinical stage and probability of survival. Plasma microRNA profiling may help to optimize existing diagnostic pathways as well as enable personalized, risk-informed melanoma treatment decisions.

Postoperative Stomach Volvulus and Pancreatitis Following a Sleeve Gastrectomy.

The laparoscopic sleeve gastrectomy is the most common bariatric surgery performed to promote weight loss and improve obesity-related comorbidities. As the number of patients undergoing sleeve gastrectomy increases, so does the prevalence of complications. It is crucial to recognize both common and unusual complications of sleeve gastrectomy to properly diagnose and manage them. We present a unique case of gastric outlet obstruction not visualized on initial imaging and acute pancreatitis following a sleeve gastrectomy. We recommend performing an endoscopy and ordering serum lipase levels in a patient with negative CT scans but persistent postoperative nausea, vomiting, and abdominal pain. The management of postoperative gastric outlet obstruction includes supportive care, balloon dilation of the stenotic area, or gastric bypass if symptoms persist.

Patient Mealtime Experience: Capturing Patient Perceptions Using a Novel Patient Mealtime Experience Tool.

INTRODUCTION: The aim of this study is to describe the mealtime experience using the qualitative components of the Austin Health Patient Mealtime Experience Tool (AHPMET) to complement the quantitative findings of this tool. METHODS: A multiphase, cross-sectional study was undertaken across all sites of Austin Health (Victoria, Australia) between March 2020 and November 2021. Patient mealtime experience was measured using the AHPMET. Descriptive statistics and a deductive thematic analysis approach described the patients' mealtime experiences. RESULTS: Questionnaire data were collected from 149 participants. Patients were most satisfied with staff interactions, and least satisfied with dimensions of food quality, specifically, flavour, presentation, and menu variety. Clinical symptoms, nutrition impact symptoms and the patient's position were barriers to consumption. DISCUSSION: Food quality was perceived as the poorest aspect of patient satisfaction with the hospital foodservice, particularly flavour, presentation, and menu variety. Future foodservice quality improvements must prioritise improving food quality to have the greatest impact on patient satisfaction. While clinical and organisational systems have a role in improving mealtime experience and oral intake, communicating patient perceptions of the mealtime experience is critical for responding to current perceptions of hospital food quality. CONCLUSION: Mealtime experience in the hospital has a significant impact on oral intake and patients' wider perception of hospital services. Questionnaires have been used to capture patient satisfaction with foodservice in the hospital; however, no comprehensive questionnaires including qualitative questions that capture the broader mealtime experience have been validated across different hospital settings. The tool developed through this study can be implemented in any acute and subacute health service to provide feedback and improve the mealtime experience of patients. This has the capacity to improve mealtime intake, mitigate malnutrition, and improve quality of life and patient outcomes.

A bird's eye view: Sexual health adviser coordination of contact tracing for hepatitis B.

An National Health Service sexual health adviser led service to facilitate management of new cases of hepatitis B from all settings across a large Scottish health board was initiated in 2012. Sexual health advisers contacted testing clinicians to support referral into appropriate services and facilitate identification, testing and vaccination of sexual partners, family and household contacts. A retrospective audit of contact tracing outcomes was conducted between September 2012 and December 2019. From a total of 1344 people diagnosed with hepatitis B, 2248 household and sexual contacts were identified. A documented outcome was established for 1741 (78%) of contacts, equalling 1.3 per index case. 257 (11%) of traced contacts were hepatitis B surface antigen positive, 162 (7%) had natural immunity and 1222 (54%) were vaccinated, either before or after contact tracing. This suggests a multi-agency approach to contact tracing for hepatitis B can achieve good outcomes. Further work is required to reduce the disproportionate burden of hepatitis B among ethnic minority subpopulations in Scotland.

Reengineering a Reversible Covalent-Bonding Assembly to Optically Detect ee in ß-Chiral Primary Alcohols.

The use of parallel synthesis protocols for asymmetric reaction discovery has increased the need for new methods to rapidly determine enantiomeric excess (ee) values. Most chirality sensing is performed on stereocenters that are α (i.e., proximal) to the target functional group. Finding a general approach to detect more distant point chirality would increase the substrate scope of such assays. Herein, we demonstrate a design principle to "reach out" to more distant stereocenters, in this case ß-chirality in primary alcohols. Therefore, we see the design principles established in this work as a step forward in sensing distant point chirality and, eventually, multi-stereocenter relationships.

Determining the effects of routine fingermark detection techniques on the subsequent recovery and analysis of explosive residues on various substrates.

An offender who has recently handled bulk explosives would be expected to deposit latent fingermarks that are contaminated with explosive residues. However, fingermark detection techniques need to be applied in order for these fingermarks to be detected and recorded. Little information is available in terms of how routine fingermark detection methods impact on the subsequent recovery and analysis of any explosive residues that may be present. If an identifiable fingermark is obtained and that fingermark is found to be contaminated with a particular explosive then that may be crucial evidence in a criminal investigation (including acts of terrorism involving improvised explosive devices). The principal aims of this project were to investigate: (i) the typical quantities of explosive material deposited in fingermarks by someone who has recently handled bulk explosives; and (ii) the effects of routine fingermark detection methods on the subsequent recovery and analysis of explosive residues in such fingermarks. Four common substrates were studied: paper, glass, plastic (polyethylene plastic bags), and metal (aluminium foil). The target explosive compounds were 2,4,6-trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), as well as chlorate and nitrate ions. Recommendations are provided in terms of the application of fingermark detection methods on surfaces that may contain explosive residues.