BAUSSS biomarker improves melanoma survival risk assessment.

BACKGROUND: The American Joint Committee on Cancer (AJCC) method of staging melanoma is dated and inaccurate. It ignores important prognostic melanoma features, especially the patient's age. BAUSSS is more accurate in determining survival risk for primary cutaneous melanoma patients who have no clinical or imaging evidence of nodal or distant metastases. BAUSSS is an algorithm incorporating analysis of Breslow thickness, Age, Ulceration, Subtype of melanoma, Sex and Site. These are the six features from the patient history along with the details from the melanoma pathology report that are most predictive of mortality outcome. OBJECTIVE: To develop a single-page document that allows the clinician to determine BAUSSS biomarker-predicted prognosis in consultation with the patient. METHOD: From various data sources, we developed an algorithm to predict melanoma mortality using the BAUSSS biomarker system. The single-page algorithm was made available to download at https://globalmelanoma.net/bausss-survival-chart, thus being readily available without charge to all clinicians and their patients. RESULTS: BAUSSS method of determining melanoma prognosis is more accurate and less costly than the AJCC staging system. The only surgery the patient requires is wide local excision of the primary tumour. This method of ascertaining melanoma risk does not require added surgery, costs, hospitalization, tests and anaesthesia, such as would be required if sentinel lymph node biopsy was undertaken. BAUSSS can be a useful tool in determining which primary melanoma patients are at sufficiently high risk to be considered for adjuvant drug therapy. CONCLUSION: We encourage clinicians to download and print in colour this single-page BAUSSS mortality prediction tool, laminate it, and use it face to face with the patient in consultations. Not only will the patient be able to recognize his/her long-term prognosis but will also be able to see how their tumour severity compares with others.

Sentinel lymph node biopsy is unreliable in predicting melanoma mortality for both younger and older patients.

BACKGROUND: Melanoma disease patterns vary with patient age. AIM: To evaluate sentinel lymph node biopsy (SLNB) in managing melanoma at differing patient ages. METHODS: Online prediction tools were applied to compare SLNB positivity (SLNB+) and survival risk at patient ages 20-80. Tübingen melanoma data were used to determine variations in the hazard ratio of SLNB+ for mortality at different patient ages. RESULTS: Regardless of tumour thickness, predicted SLNB+ rates were markedly higher than mortality rates for 20-year-old patients. For 80-year-old patients, it is the opposite. DISCUSSION: If 1000 20-year-olds with a 0.4 mm thickness non-ulcerated melanoma underwent SLNB, 100 would likely be positive. If all 100 were to be offered adjuvant drug therapy (ADT), fewer than three more melanoma deaths in those 1000 patients would be avoided. In total, 97 patients would have received medication they may never have needed. If 1000 80-year-olds with a 3 mm thickness non-ulcerated melanoma underwent SLNB, only 40 would likely be positive. In total, 274 patients would be predicted to die of melanoma, 245 being SLNB negative and 29 SLNB+. ADT linked to SLNB+ could deny treatment to 89% of these high-risk patients. LIMITATIONS: The authors relied on published risk data. CONCLUSION: SLNB has poor specificity at predicting mortality in young melanoma patients and poor sensitivity in older patients. SLNB is not indicated in managing cutaneous melanoma for patients under 40 or over 60 years of age. Many such patients could be managed with wide local excision alone in their clinician's office-based practice. For all cutaneous melanoma patients at all ages, linking ADT to BAUSSS biomarker, (an algorithm of Breslow thickness, age, ulceration, subtype, sex and Site) rather than SLNB+ is likely more appropriate. BAUSSS provides a more accurate melanoma-specific mortality risk assessment for patients without burdening them with added surgery, hospitalization, costs or morbidity risk.

Keratoacanthoma: Update on the Debate.

ABSTRACT: Keratoacanthoma (KA) is a cutaneous tumor with a biphasic pattern of growth. A rapidly growing phase is usually followed by involution. KA occurs on sun-damaged skin. There are many listed causative associations, which include some therapeutic agents. Debate continues as to whether KA is a variant of squamous carcinoma (SCC) or a separate entity. Reporting of KA versus SCC is markedly inconsistent. Reasons for inconsistency include overlapping microscopic criteria, variants of KA with more aggressive features, and possibly medicolegal concerns. Genetic studies have shown some differences between the 2 entities. Activation of apoptotic pathways has been demonstrated in KA. Genetic studies have shown a possible role of human polyomavirus 6 in the pathogenesis of at least some KAs. Given that some cases of KA have components that behave as conventional SCCs, KA can be considered as a low-grade variant of SCC with some genetic differences.

Small area variation in crime effects of COVID-19 policies in England and Wales.

Purpose: The aim of this study is to examine small area variation in crime trajectories during the COVID-19 pandemic in England and Wales. While we know how police-recorded crime responded to lockdown policies at the 'macro' level, less is known about the extent to which these trends were experienced uniformly at localized spatial scales. Methods: Longitudinal k-means clustering is used to unpick local area variation in police notifiable offences across England and Wales. We describe the clusters identified in terms of their spatial patterning, opportunity structures and crime type profile. Results: We find that in most small areas, crime remained fairly stable throughout the pandemic. Instead, a small number of meso-level areas contributed a disproportionately large amount to the macro-level trend. These were typically city centers with plentiful pre-pandemic crime opportunities, dominated by theft and shoplifting offences. Conclusion: Findings offer support for opportunity theories of crime and for a mobility theory of crime during the pandemic. We explore potential implications for policy, theory and further research.

Revised Mohs surgery care guidelines for squamous cell carcinoma in-situ are overdue.

The treatment of cutaneous squamous cell carcinoma in situ by Mohs micrographic surgery is currently deemed as appropriate by the Mohs Appropriate Use Criteria. However, squamous cell carcinoma in situ is a very superficial, indolent, low-risk tumor amenable to destructive and non-surgical treatments. It is uncommon for squamous cell carcinoma in situ to have progressed to invasive malignancy subsequent to definitive management. The suggestion that squamous cell carcinoma in situ on certain anatomic locations has a poorer prognosis is widely assumed but lacks an evidence base. We recommend that most primary squamous cell carcinoma in situ in non-immunosuppressed patients be scored inappropriate or uncertain for Mohs micrographic surgery by the Mohs Appropriate Use Criteria. Multiple other efficacious treatment options exist for managing squamous cell carcinoma in situ, including curettage and cryotherapy, curettage and electrodessication, and topical therapies.

Learning curves and surgical outcomes for proctored adoption of laparoscopic ventral mesh rectopexy: cumulative sum curve analysis.

BACKGROUND: Laparoscopic ventral mesh rectopexy (VMR) is an effective and well-recognised treatment for symptoms of obstructive defecation in the context of rectal prolapse and recto-rectal intussusception. However, due to the technical complexity of VMR, a significant learning curve has been previously described. This paper examines the effect of proctored adoption of VMR on learning curves, operative times, and outcomes. METHODS: A retrospective database analysis of two district general hospitals was conducted, with inclusion of all cases performed by two surgeons since first adoption of the procedure in 2007-2015. Operative time, length of stay, and in-hospital complications were evaluated, with learning curves assessed using cumulative sum curves. RESULTS: Three hundred and eleven patients underwent VMR during the study period and were included for analysis. Patients were near-equally distributed between surgeons (surgeon A: n = 151, surgeon B, n = 160) with no significant differences between gender, age, or ASA grade. In-hospital morbidity was 3.2 %, with 0 % mortality. Cumulative sum curve analysis suggested a change point of between 25 and 30 cases based on operative times and length of stay and was similar between both surgeons. No significant change point was seen for morbidity or mortality. CONCLUSION: VMR is an effective and safe treatment for rectal prolapse. Surgeons in this study were proctored during the adoption process by another surgeon experienced in VMR; this may contribute to increased safety and abbreviated learning curve. In the context of proctored adoption, this study estimates a learning curve of 25-30 cases, without detrimental impact on patient outcomes.

A Multicenter Collaboration to Assess the Safety of Laparoscopic Ventral Rectopexy.

BACKGROUND: Concerns have been raised regarding the potential risk of mesh complications after laparoscopic ventral rectopexy. OBJECTIVE: This study aimed to determine the risk of mesh and nonmesh morbidity after laparoscopic ventral rectopexy and to compare the safety of synthetic meshes with biological grafts. DESIGN: This was a retrospective review. SETTINGS: The study used data collated from prospective pelvic floor databases in 5 centers (3 in the United Kingdom, 1 in Australia, and 1 in Italy). PATIENTS: All of the patients undergoing laparoscopic ventral rectopexy over a 14-year period (1999-2013) at these centers were included in the study. MAIN OUTCOME MEASURES: The primary outcome was mesh morbidity, classified as vaginal erosion, rectal erosion, rectovaginal fistula, or perineal erosion. Secondary outcomes were nonmesh morbidity. RESULTS: A total of 2203 patients underwent surgery; 1764 (80.1%) used synthetic mesh and 439 (19.9%) used biological grafts. There were 2 postoperative deaths (0.1%). Forty-five patients (2.0%) had mesh erosion, including 20 vaginal, 17 rectal, 7 rectovaginal fistula, and 1 perineal. Twenty-three patients (51.1%) required treatment for minor erosion morbidity (local excision of stitch/exposed mesh), and 18 patients (40.0%) were treated for major erosion morbidity (12 laparoscopic mesh removal, 3 mesh removal plus colostomy, and 3 anterior resection). Erosion occurred in 2.4% of synthetic meshes and 0.7% of biological meshes. The median time to erosion was 23 months. Nonmesh complications occurred in 11.1% of patients. LIMITATIONS: This was a retrospective study including patients with minimal follow-up. The study was unable to determine whether patients will develop future erosions, currently have asymptomatic erosions, or have been treated in other institutions for erosions. CONCLUSIONS: Laparoscopic ventral rectopexy is a safe operation. Mesh erosion rates are 2% and occasionally require resectional surgery that might be reduced by the use of biological graft. An international ventral mesh registry is recommended to monitor mesh problems and to assess whether type of mesh has any impact on functional outcomes or the need for revisional surgery for nonerosion problems.

Novel photodynamic therapy does not prevent new skin cancers--randomized controlled trial.

OBJECTIVES: To determine whether field photodynamic therapy (PDT) of actinic keratoses using a novel preparation of 5-aminolevulonic acid (novel ALA) results in fewer subsequent invasive skin cancers developing on the face of individuals with previous facial cutaneous malignancy in a prospective randomized controlled trial. METHODS AND MATERIALS: Intervention patients received two treatments of novel ALA 2 weeks apart. Controls were observed. Patients were followed up with biopsy of any suspicious lesions for 3 years. RESULTS: The trial was suspended early because of problems with trial governance and the reporting of severe adverse events. Sixty-four patients who were recruited at that time at one center were monitored. Their average age was 71, and 57% were male. Patients were randomized to intervention (n = 34) or observation (n = 29). Over the subsequent 3 years, 13 intervention patients (38%) developed 30 new cutaneous malignancies in the field treated, and 11 control patients (38%) developed 22 new malignancies. Some intervention patients experienced prolonged adverse events, including permanent scarring. CONCLUSION: Novel ALA made no difference in the likelihood of new malignancies developing. The risks without benefit of this novel ALA are troubling. Lack of efficacy and safety of novel ALA cannot be extrapolated to other PDT products.

Prolonged adverse events following photodynamic therapy: regulatory implications.

OBJECTIVE: To determine whether field photodynamic therapy (PDT) of actinic keratoses (AKs) using a novel preparation of 5-aminolevulonic acid (ALA) would result in fewer subsequent invasive skin cancers developing on the face. DESIGN: A prospective multi-center randomized controlled trial. The protocol was approved by the Bond University Human Research Ethics Committee in accord with the TGA's Clinical Trial Notification Scheme. The trial was registered (12609000025235) on the Australian New Zealand Clinical Trials Registry. SETTING: Six centers in four states in Australia. PROTOCOL: Two treatments of ALA PDT, 2 weeks apart for each patient. Controls were observed. Patients were followed up with biopsies of any suspicious lesions every 6 months for 2 years. MAIN OUTCOME MEASURE(S): Development of new skin cancers. RESULTS: The trial was suspended after 3 months and closed after 6 months after ethics committee approval was withdrawn on the basis of a breakdown in trial governance. Over the following 2 years, some investigators noted and formally reported the continued occurrence of serious adverse events in excess of those described with other approved cutaneous PDT treatments. USA dermatologists with experience managing AKs with FDA approved ALA products subsequently confirmed prolonged and severe adverse events in 6 of the former trial intervention patients. DISCUSSION AND CONCLUSIONS: Adverse effects experienced by patients using the investigational ALA PDT appeared more severe than those experienced when an FDA-approved ALA product is used. We believe the former should be further evaluated for safety. It is of concern that this ALA product and lamp could be promoted and used widely in Australia following these reports of significant adverse events and continued lack of TGA approval.

Sentinel lymph node biopsy now has a limited role in melanoma management.

SLNB is confirmed as a prognostic test but does not influence melanoma-specific survival at 10 years. SLNB-negative patients still need regular review and can still die from their melanoma. SLNB-positive patients should be carefully counselled regarding the risks and very limited benefit (if any) of proceeding to CL. SLNB should not be regarded as essential or standard of care for patients with melanomas. SLNB should be discussed with patients with intermediate-thickness melanoma. Note that 'discuss' is not the same as 'offer' or 'recommend'. The discussion should include: • SLNB does not alter survival prospects • SLNB provides added accuracy to survival prognostic figures−−70% vs. 90% for melanoma Breslow thickness of 1.2­3.5 mm • SLNB has a 10% complication rate • If positive, no added treatment can be offered that has demonstrated survival benefits−− this includes no apparent survival benefit in proceeding to CL−− SLNB-positive patients can be offered enrolment into further melanoma studies.

Primary Cutaneous Melanoma-Management in 2024.

Background: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. Objective: to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. Methods: We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. Results: We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. Discussion: Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.

Domestic abuse in the Covid-19 pandemic: measures designed to overcome common limitations of trend measurement.

Research on pandemic domestic abuse trends has produced inconsistent findings reflecting differences in definitions, data and method. This study analyses 43,488 domestic abuse crimes recorded by a UK police force. Metrics and analytic approaches are tailored to address key methodological issues in three key ways. First, it was hypothesised that reporting rates changed during lockdown, so natural language processing was used to interrogate untapped free-text information in police records to develop a novel indicator of change in reporting. Second, it was hypothesised that abuse would change differentially for those cohabiting (due to physical proximity) compared to non-cohabitees, which was assessed via a proxy measure. Third, the analytic approaches used were change-point analysis and anomaly detection: these are more independent than regression analysis for present purposes in gauging the timing and duration of significant change. However, the main findings were largely contrary to expectation: (1) domestic abuse did not increase during the first national lockdown in early 2020 but increased across a prolonged post-lockdown period, (2) the post-lockdown increase did not reflect change in reporting by victims, and; (3) the proportion of abuse between cohabiting partners, at around 40 percent of the total, did not increase significantly during or after the lockdown. The implications of these unanticipated findings are discussed. Supplementary Information: The online version contains supplementary material available at 10.1186/s40163-023-00190-7.

Anti-social behaviour in the coronavirus pandemic.

Anti-social behaviour recorded by police more than doubled early in the coronavirus pandemic in England and Wales. This was a stark contrast to the steep falls in most types of recorded crime. Why was ASB so different? Was it changes in 'traditional' ASB such as noisy neighbours, or was it ASB records of breaches of COVID-19 regulations? Further, why did police-recorded ASB find much larger early-pandemic increases than the Telephone Crime Survey for England and Wales? This study uses two approaches to address the issues. The first is a survey of police forces, via Freedom of Information requests, to determine whether COVID-regulation breaches were recorded as ASB. The second is natural language processing (NLP) used to interrogate the text details of police ASB records. We find police recording practice varied greatly between areas. We conclude that the early-pandemic increases in recorded ASB were primarily due to breaches of COVID regulations but around half of these also involved traditional forms of ASB. We also suggest that the study offers proof of concept that NLP may have significant general potential to exploit untapped police text records in ways that inform policing and crime policy.

Illegal waste fly-tipping in the Covid-19 pandemic: enhanced compliance, temporal displacement, and urban-rural variation.

Objective: Illegal dumping of household and business waste, known as fly-tipping in the UK, is a significant environmental crime. News agencies reported major increases early in the COVID-19 pandemic when waste disposal services were closed or disrupted. This study examines the effect of lockdowns on illegal dumping in the UK. Method: A freedom of information request was sent to all local authorities in the UK asking for records of reported incidents of fly-tipping for before and after the first national lockdown. ARIMA modelling and year-on-year comparison was used to compare observed and expected levels of fly-tipping. Urban and rural local authorities were compared. Results: A statistically significant decline in fly-tipping during the first lockdown was followed by a similar increase when lockdown ended. The effects largely cancelled each other out. There was pronounced variation in urban-rural experience: urban areas, with higher rates generally, experienced most of the initial drop in fly-tipping while some rural authorities experienced an increase. Conclusion: Waste services promote compliance with laws against illegal dumping. When those services were disrupted during lockdown it was expected that fly-tipping would increase but, counter-intuitively, it declined. This enhanced compliance effect was likely due to increased perceived risk in densely populated urban areas. However, as lockdown restrictions were eased, fly-tipping increased to clear the backlog, indicating temporal displacement. Supplementary Information: The online version contains supplementary material available at 10.1186/s40163-022-00170-3.

Prey life-history influences the evolution of egg mass and indirectly reproductive investment in a group of free-living insect predators.

The balance between risk and benefit of exploiting resources drives life-history evolution in organisms. Predators are naturally recognized as major drivers of the life-history evolution of their prey. Although prey may also influence the life-history evolution of their predators in the context of an evolutionary arms race, there is far more evidence of the role of predators than of prey.The goal of this study was to investigate the role of prey in life-history evolution of predators using ladybird beetle predators of aphids and coccids. These particular ladybirds and their prey were chosen because literature shows that the pace of life of aphids is faster than that of coccids and this difference is reflected in the life histories of the ladybirds that specialize on feeding on aphids or coccids.Thirty-four species of ladybird predators of aphids and eight of coccids belonging to five different tribes were collected and reared in the laboratory. The females were weighed as well as their eggs, and their reproductive investment estimated as the number of ovarioles. Phylogenetic relatedness was controlled for in the statistical analyses.Controlling for female mass revealed that ladybird predators of aphids lay bigger eggs than ladybird predators of coccids. This difference is not influenced by phylogenetic relatedness but only by the type of prey eaten. We suggest that ladybird predators of coccids lay smaller eggs because neonate larvae do not have to search, catch, and subdue prey. Both types of ladybirds have a similar reproductive investment relative to their body mass when phylogeny is controlled for.Recognizing the influence of prey on the life-history evolution of predators is important for understanding food web dynamics. From an applied perspective, this fine evolutionary tuning of prey-predator relationships should be used to guide and increase the efficiency of biological control programs.