How Dermatologic Surgeons Decide to Proceed with Surgery for Nonmelanoma Skin Cancer When Site Identification is Initially Uncertain: A Nationwide, Multicenter, Prospective Study.

BACKGROUND: Few studies show how dermatologic surgeons manage problems with site identification. OBJECTIVE: To estimate frequency and characterize management of skin cancer treated by surgery when the anatomic location of the tumor is in question. METHODS: Nationwide, prospective, multi-site cohort study. RESULTS: Among 17,076 cases at 22 centers, 98 (0.60%) were lesions in question (LIQ) for which site identification was initially uncertain, with these more often in patients who were male, older, and biopsied more than 30 days ago. Surgeons employed on average 5.0 (95% CI: 4.61-5.39) additional techniques to confirm the site location, with common approaches including: re-checking available documentation (90 lesions, 92%); performing an expanded physical examination (89 lesions, 91%); and asking the patient to point using a mirror (61 lesions, 62%). In 15%, photographs were requested from the biopsying provider, and also in 15%, frozen section biopsies were obtained. In 10%, the referring physician was contacted. Eventually, surgeons succeeded in definitively identifying 82% (80/98) of initially uncertain sites, with the remaining 18% (18/98) postponed. Most postponed surgeries were at non-facial sites. LIMITATIONS: Sites were academic centers. CONCLUSIONS: When the anatomic location of the tumor is uncertain, dermatologic surgeons use multiple methods to identify the site, and sometimes cases are postponed.

Sexual Activity, Function, and Satisfaction in Reproductive-Aged Females Living with Chronic Kidney Disease.

Up to 80% of women living with chronic kidney disease (CKD) experience sexual dysfunction, though its link with sexual activity and sexual satisfaction is not well understood. Among older women with CKD treated with hemodialysis, the majority report sexual inactivity, though few describe sexual difficulty and most report high sexual satisfaction. Whether this applies to reproductive-aged females living with CKD is yet unknown. This study aimed to assess the sexual activity, function, and satisfaction of reproductive-aged females living with CKD. Self-identified females aged 18-51 years with CKD were recruited from nephrology clinics in Calgary, Canada. Sexual activity, function, and satisfaction were assessed with a modified version of the Female Sexual Function Index. Fifty-seven participants were recruited (35% CKD without kidney replacement therapy, 44% CKD treated with hemodialysis, 9% CKD treated with peritoneal dialysis, 12% CKD treated with kidney transplant) and nearly half (47%) reported sexual activity. Among sexually active participants, there was a high prevalence of sexual dysfunction (67%) and only 25% of participants reported sexual satisfaction. A strong relationship between sexual function and satisfaction was identified. Reproductive-aged females living with CKD are sexually active, though experience high rates of sexual dysfunction and dissatisfaction. These findings emphasize the importance of recognition and management of sexual dysfunction in this important population.

Cardiovascular disease and stroke following cancer and cancer treatment in older adults.

BACKGROUND: Cancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort. METHODS: The authors conducted a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate the impact of cancer and cancer treatment on a composite CVD end point comprising hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke. RESULTS: Of 15,454 Australian and US ASPREE participants, 1392 had an incident cancer diagnosis. Rates of CVD were greater in the cancer risk-set compared to the cancer-free risk-set (20.8 vs. 10.3 events per 1000 person-years; incidence rate ratio, 2.03; 95% confidence interval, 1.51-2.66), with increased incidence seen across MI, HHF, overall stroke, and ischemic stroke. Increased incidence remained after adjustment for clinically significant risk factors for CVD. Incidence was greatest in metastatic, hematological, and lung cancer. Chemotherapy was associated with increased risk of CVD. Similar rates of CVD were seen across aspirin and placebo groups. CONCLUSIONS: Incidence of CVD, including MI, HHF, and ischemic stroke, was increased in older adults with cancer. Aspirin did not impact CVD incidence. Risk may be higher in those with metastatic, hematological, and lung cancer, and following chemotherapy.

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

BACKGROUND: Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20 years. Limited data exist on CMMRD-associated lymphomas and their outcome. METHODS: We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. FINDINGS: The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4 years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7 years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. INTERPRETATION: Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

Quantitative NMR Analysis of Marine Macroalgae for AGE Inhibition by Methylglyoxal Scavenging.

Reactive carbonyl species (RCS) induce a fundamental form of biological stress that has driven the evolution of diverse mechanisms for minimizing its impact on organismal health. The complications that accompany uncontrolled hyperglycemia exemplify the health implications when RCS stress exceeds the body's capacity to prevent the excessive formation of advanced glycation end-products. Presented here is a novel quantitative NMR (qNMR) technique for evaluating scavengers of the prominent sugar-derived carbonyl methylglyoxal (MGO). This tool was employed to screen the chemical diversity of marine macroalgae extracts, with a focus on species that have a history of consumption by the World's healthiest populations and are subject to global scale aquacultural production. Fucus vesiculosus demonstrated the highest capacity for inhibiting glycation and scavenging MGO. Additionally, the Chondrus cripsus, Gracilaria vermiculophyla, and Gracilaria tikvahiae extracts had a high capacity for scavenging MGO, representing the first report of this activity. This new qNMR methodology presented is highly applicable for screening extracts and compounds from diverse sources, and the results highlight the potential of macroalgae extracts to be employed as RCS and AGE targeting therapeutics and food additives.

Evaluation of research co-design in health: a systematic overview of reviews and development of a framework.

BACKGROUND: Co-design with consumers and healthcare professionals is widely used in applied health research. While this approach appears to be ethically the right thing to do, a rigorous evaluation of its process and impact is frequently missing. Evaluation of research co-design is important to identify areas of improvement in the methods and processes, as well as to determine whether research co-design leads to better outcomes. We aimed to build on current literature to develop a framework to assist researchers with the evaluation of co-design processes and impacts. METHODS: A multifaceted, iterative approach, including three steps, was undertaken to develop a Co-design Evaluation Framework: 1) A systematic overview of reviews; 2) Stakeholder panel meetings to discuss and debate findings from the overview of reviews and 3) Consensus meeting with stakeholder panel. The systematic overview of reviews included relevant papers published between 2000 and 2022. OVID (Medline, Embase, PsycINFO), EBSCOhost (Cinahl) and the Cochrane Database of Systematic reviews were searched for papers that reported co-design evaluation or outcomes in health research. Extracted data was inductively analysed and evaluation themes were identified. Review findings were presented to a stakeholder panel, including consumers, healthcare professionals and researchers, to interpret and critique. A consensus meeting, including a nominal group technique, was applied to agree upon the Co-design Evaluation Framework. RESULTS: A total of 51 reviews were included in the systematic overview of reviews. Fifteen evaluation themes were identified and grouped into the following seven clusters: People (within co-design group), group processes, research processes, co-design context, people (outside co-design group), system and sustainment. If evaluation methods were mentioned, they mainly included qualitative data, informal consumer feedback and researchers' reflections. The Co-Design Evaluation Framework used a tree metaphor to represent the processes and people in the co-design group (below-ground), underpinning system- and people-level outcomes beyond the co-design group (above-ground). To evaluate research co-design, researchers may wish to consider any or all components in the tree. CONCLUSIONS: The Co-Design Evaluation Framework has been collaboratively developed with various stakeholders to be used prospectively (planning for evaluation), concurrently (making adjustments during the co-design process) and retrospectively (reviewing past co-design efforts to inform future activities).

Global changes and their environmental stressors have a significant impact on soil biodiversity-A meta-analysis.

Identifying the main threats to soil biodiversity is crucial as soils harbor ∼60% of global biodiversity. Many previous meta-analyses investigating the impact of different global changes (GCs) on biodiversity have omitted soil fauna or are limited by the GCs studied. We conducted a broad-scale meta-analysis focused on soil fauna communities, analyzing 3,161 effect sizes from 624 publications studying climate change, land-use intensification, pollution, nutrient enrichment, invasive species and habitat fragmentation. Land-use intensification resulted in large reductions in soil fauna communities, especially for the larger-bodied groups. Unexpectedly, pollution caused the largest negative impact on soil biodiversity - particularly worrying due to continually increasing levels of pollution and poor mechanistic understanding of impacts relative to other GCs. Not all GCs and stressors were detrimental; organic-based nutrient enrichment often resulted in positive responses. Including soil biodiversity in large-scale analyses is vital to fully understand the impact of GCs across the different realms.

Streamlined Clinical Management Pathways May Reduce Major Amputations in Patients with Chronic Limb Threatening Ischaemia: A Prospective Cohort Study with Historical Controls.

OBJECTIVE: Patient characteristics and patterns of disease in chronic limb threatening ischaemia (CLTI) have changed markedly in recent years. Urgent specialist referral and timely revascularisation are recommended in international guidelines. UK guidelines now recommend revascularisation within 5 days of referral for inpatients and 2 weeks in outpatients. This study compared the contemporary one year major amputation incidence in patients with CLTI with a historical cohort at a single UK centre. METHODS: This was a single centre, observational cohort study with historical controls. A prospective cohort was recruited between May 2019 and March 2022. A historical cohort presenting between 2013 and 2015 inclusive was identified retrospectively. Significant changes in management pathways, including establishing a rapid access limb salvage clinic, occurred between these periods aiming to expedite time from referral to revascularisation. The one year primary outcome was major amputation, and the secondary outcome was death. Major amputation was analysed by Fine-Gray competing risks models (death as the competing risk), presented as subdistribution hazard ratios (SHRs). One year mortality was analysed by Cox regression, presented as hazard ratios. Analyses were adjusted for propensity score. RESULTS: A total of 928 patients were included (432 prospective and 496 historical). Proportions of patients presenting with tissue loss (72.2% vs. 71.6%; p = .090) were similar in both cohorts. At one year, 48 patients (11.1%) in the prospective cohort and 124 patients (25.0%) in the historical cohort had undergone a major amputation (p < .001). Risk of major amputation was 57.0% lower in the prospective cohort compared with the historical cohort after adjustment for propensity score (SHR 0.43, 95% confidence interval 0.29 - 0.63; p < .001). CONCLUSION: An encouraging reduction in major amputation incidence was observed after improvements to CLTI management pathways, but residual confounding is likely. The generalisability of these results is uncertain.

Individual, social and area level factors associated with older people's walking: Analysis of an UK household panel study (Understanding Society).

BACKGROUND: Among older people, walking is a popular and prevalent activity. Walking is key to increasing physical activity levels and resulting physical and mental health. In the context of rapidly ageing populations, it is important to better understand what factors are associated with walking among older people, based on the socioecological model of health. METHODS: We used data from Understanding Society (n:6450), a national panel survey of UK adults aged 65 years and over living in Great Britain. Slope Indices of Inequality (SII) were calculated for weekly walking hours for older people according to individual, social and area characteristics. These include health, loneliness and social isolation, previous walking and sporting activity, residential self-selection, contact with neighbours, number of close friends and social activity. Spatial area-level data described local area crime, walkability, and proximity to retail, greenspace, and public transport amenities. RESULTS: Multivariable models indicated that poor health, particularly requiring help with walking, was the strongest predictor of weekly walking hours (SII (95% CI) comparing those needing help vs. no help: -3.58 (-4.30, -2.87)). However, both prior sporting activity (most vs. least active: 2.30 (1.75, 2.88)) and walking for pleasure (yes vs. no: 1.92 (1.32, 2.53)) were strongly associated with increased walking several years later. Similarly having close friends (most vs. fewest, 1.18 (0.72, 1.77)) and local retail destinations (any vs. none: 0.93 (0.00, 1.86)) were associated with more weekly walking. CONCLUSIONS: Past engagement in physical activity and walking for pleasure are strong predictors of walking behaviour in older people, underscoring the importance of implementing and sustaining walking interventions across the lifespan to ensure continued engagement in later years and the associated health benefits. However, poor health significantly impedes walking in this demographic, emphasising the need for interventions that offer both physical assistance and social support to promote this activity.

Thrombin Generation Is Associated With Extracellular Vesicle and Leukocyte Lipid Membranes in Atherosclerotic Cardiovascular Disease.

BACKGROUND: Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples. METHODS: Thrombin generation was measured using a purified factor assay on platelet, leukocyte, and extracellular vesicles (EVs) from patients with acute coronary syndrome (n=24), stable coronary artery disease (n=18), and positive risk factor (n=23) and compared with healthy controls (n=24). aPL composition of resting/activated platelet and leukocytes and EV membranes was determined using lipidomics. RESULTS: External facing aPLs were detected on EVs, platelets, and leukocytes, elevating significantly following cell activation. Thrombin generation was higher on the surface of EVs from patients with acute coronary syndrome than healthy controls, along with increased circulating EV counts. Thrombin generation correlated significantly with externalized EV phosphatidylserine, plasma EV counts, and total EV membrane surface area. In contrast, aPL levels and thrombin generation from leukocytes and platelets were not impacted by disease, although circulating leukocyte counts were higher in patients. CONCLUSIONS: The aPL membrane of EV supports an elevated level of thrombin generation in patient plasma in ASCVD. Leukocytes may also play a role although the platelet membrane did not seem to contribute. Targeting EV formation/clearance and developing strategies to prevent the aPL surface of EV interacting with coagulation factors represents a novel antithrombotic target in ASCVD.

The role of kinesin-1 in neuronal dense core vesicle transport, locomotion and lifespan regulation in C. elegans.

Fast axonal transport is crucial for neuronal function and is driven by kinesins and cytoplasmic dynein. Here, we investigated the role of kinesin-1 in dense core vesicle (DCV) transport in C. elegans, using mutants in the kinesin light chains (klc-1 and klc-2) and the motor subunit (unc-116) expressing an ida-1::gfp transgene that labels DCVs. DCV transport in both directions was greatly impaired in an unc-116 mutant and had reduced velocity in a klc-2 mutant. In contrast, the speed of retrograde DCV transport was increased in a klc-1 mutant whereas anterograde transport was unaffected. We identified striking differences between the klc mutants in their effects on worm locomotion and responses to drugs affecting neuromuscular junction activity. We also determined lifespan, finding that unc-116 mutant was short-lived whereas the klc single mutant lifespan was wild type. The ida-1::gfp transgenic strain was also short-lived, but surprisingly, klc-1 and klc-2 extended the ida-1::gfp lifespan beyond that of wild type. Our findings suggest that kinesin-1 not only influences anterograde and retrograde DCV transport but is also involved in regulating lifespan and locomotion, with the two kinesin light chains playing distinct roles.

Are we joining the One Health dots? A scoping review of research on the one health effects of extreme weather events in eastern Australia.

Extreme weather events such as floods, bushfires, cyclones, and drought, are projected to increase in eastern Australia. Understanding how these events influence the combined, sustainable well-being of humans, animals, and ecosystems - that is One Health - will enable development of transdisciplinary and ultimately more effective interventions. A scoping review was conducted to explore the research associated with the effects of extreme weather events in eastern Australia using a One Health lens, specifically identifying the type of extreme weather events studied, the research conducted in the context of One Health, and gaps to inform improved One Health implementation. The review followed JBI guidelines (based on PRISMA). Eligible research was peer-reviewed, in English, and published since 2007, in which primary research studies investigated the impact of extreme weather events in eastern Australia on at least two of ecosystems, human health, and animal health. Using structured search terms, six databases were searched. Following removal of duplicates, 870 records were screened by two reviewers. Eleven records were eligible for data extraction and charting. The scope of extreme weather events studied was relatively limited, with studies in flood and bushfire settings predominating, but relatively little research on cyclones. Major health themes included more than the impact of extreme weather events on physical health (zoonotic and vector-borne diseases) through investigation of social well-being and mental health in the context of the human-animal bond in evacuation behaviors and drought. Research gaps include studies across a broader range of extreme weather events and health topics, as well as a more comprehensive approach to including the impacts of extreme weather events on all three domains of One Health. The limited research focus inevitably translates to limited recommendations for policy, planning and response to manage extreme weather event emergencies. Given the expected increase in frequency of these events, there is a critical need for more comprehensive primary research to better identify strategies and facilitate implementation of One Health promotion for improved outcomes in extreme weather event emergencies.

Assessing patient autonomy in the context of TeamBirth, a quality improvement intervention to improve shared decision-making during labor and birth.

BACKGROUND: Respectful maternity care includes shared decision-making (SDM). However, research on SDM is lacking from the intrapartum period and instruments to measure it have only recently been developed. TeamBirth is a quality improvement initiative that uses team huddles to improve SDM during labor and birth. Team huddles are structured meetings including the patient and full care team when the patient's preferences, care plans, and expectations for when the next huddle will occur are reviewed. METHODS: We used patient survey data (n = 1253) from a prospective observational study at four U.S. hospitals to examine the relationship between TeamBirth huddles and SDM. We measured SDM using the Mother's Autonomy in Decision-Making (MADM) scale. Linear regression models were used to assess the association between any exposure to huddles and the MADM score and between the number of huddles and the MADM score. RESULTS: In our multivariable model, experiencing a huddle was significantly associated with a 3.13-point higher MADM score. When compared with receiving one huddle, experiencing 6+ huddles yielded a 3.64-point higher MADM score. DISCUSSION: Patients reporting at least one TeamBirth huddle experienced significantly higher SDM, as measured by the MADM scale. Our findings align with prior research that found actively involving the patient in their care by creating structured opportunities to discuss preferences and choices enables SDM. We also demonstrated that MADM is sensitive to hospital-based quality improvement, suggesting that future labor and birth interventions might adopt MADM as a patient-reported experience measure.

Uncovering molecular mechanisms for amelanotic/hypopigmented primary cutaneous melanoma.

BACKGROUND: A portion of approximately 2-20% of cutaneous melanoma (CM) are diagnosed as amelanotic/hypopigmented melanoma (AHM) and represent a challenge for early diagnosis. OBJECTIVES: Since the degree to which somatic mutations and copy number aberrations (CNA) in genes associated with skin-lightening or albinism may contribute to the loss of tumour pigmentation in AHM samples has not yet been addressed, we have investigated loss of function mutations of key pigmentation genes in matched germline and AHM as well as pigmented melanoma (PM) tumour DNA samples. METHODS: An analysis of clinical and histopathological characteristics together with whole exome sequencing data of 34 fresh frozen primary CM, graded according to the amount of pigmentation present was performed. Together with germline and somatic variant analysis, 30 samples were previously analysed for CNA changes. This study focussed on germline and somatic variants in the coding region of 16 genes known to be associated with albinism/hypopigmentation or variation in human pigmentation in all samples. Chromosomal regions encompassing these 16 genes were examined for DNA copy loss or gain. RESULTS: The finding that red hair related MC1R and TYR R402Q loss of activity gene variant alleles and genotypes are associated with AHM was validated in this study. Germline AHM-related gene variants were enriched in 70% (n=7 of 10) of AHM patients vs 8.3% (n=2 of 24) of PM patients. This surprisingly high frequency of rare germline variants in AHM patients constitutes the "first hit" and confirms that AHM patients are more likely to be albinism allele carriers than patients with PM. Next, in CNA analysis of each tumour sample, 50% (n=4 of 8) AHM samples with a pigmentation gene variant had LOH in the region containing the corresponding gene, and 25% (=2 of 8) had loss-of-heterozygosity (LOH) in chromosomal regions of two AHM-related genes. CONCLUSIONS: This study proposes that the likely molecular mechanism for development of amelanogenesis in AHM is carriage of an albinism/hypopigmentation allele followed by LOH of the corresponding gene in the tumour.

Integration and validation of host transcript signatures, including a novel 3-transcript tuberculosis signature, to enable one-step multiclass diagnosis of childhood febrile disease.

BACKGROUND: Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression. METHODS: We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics. RESULTS: Samples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822-0.972]; DB from DV with AUC of 0.825 [0.691-0.959] (signature-1) and 0.867 [0.753-0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787-0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808-1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%). CONCLUSIONS: Our study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups.

Maintenance of response to ketogenic diet therapy for drug-resistant epilepsy post diet discontinuation: A multi-centre case note review.

PURPOSE: There is limited research on the proportion of individuals with epilepsy who maintain response to ketogenic diet therapy (KDT) after discontinuing treatment. We aimed to determine the proportion of individuals who did / did not maintain response post KDT and explore factors that may influence the likelihood of maintaining response. METHODS: Retrospective data were collected from 97 individuals from 9 KDT centres. Individuals had achieved ≥50 % seizure reduction on KDT for at least 12 months, with seizure frequency data available at 3 months+ post diet. Outcome 1 was: recurrence of seizures or increase in seizure frequency post diet; outcome 2: recurrence of seizures, increase in seizure frequency or an additional anti-seizure treatment started post diet. RESULTS: 61/97 (62.9 %) individuals maintained response at latest follow-up (mean 2.5[2.0] years since stopping KDT). Approximately one third maintained response without further anti-seizure treatments. One quarter of individuals had an increase in frequency or recurrence of seizures within 6 months (95 %CI 4, 12) for outcome 1 and within 3 months (3, 6) for outcome 2. Individuals who did not achieve seizure freedom on diet were significantly more likely to have an increase in seizures or to require additional anti-seizure treatments post diet compared to those who were seizure-free on diet (hazard ratio 4.02, 95 %CI (1.46, 11.16) p < 0.01). CONCLUSION: Our findings should help guide clinical teams with the information they provide patients and their families regarding likelihood of long-term seizure response to KDT. Realistic costings for KDT services may need to be considered.

Nice to know 2: The impact of NICE guidelines on ketogenic diet services in the UK and Ireland - An update.

BACKGROUND: Ketogenic diet therapy (KDT) has been recommended as a treatment for drug-resistant epilepsy in children and young people since 2012 in the National Institute for Health and Care Excellence Clinical Guidelines for Epilepsies. The Ketogenic Dietitians Research Network completed a survey in 2017 to assess the impact of these guidelines. METHODS: An online survey was circulated to ketogenic dietitians across the UK and Ireland. The results were compared with those of the 2017 survey. RESULTS: The number of individuals following KDT was 854, comprising an increase of 13% since 2017. Service sizes ranged widely, with 1-74 (median 16) patients on the diet. Of 36 services, 30 had a waiting list, ranging from 2 to 67 (median 9) patients. The classical diet continued to be the most common KDT used (58% of patients). Ten services reported use of a new flexible medium chain triglyceride protocol. Some 48% of patients (n = 427) had been following the KDT for over 2 years, comprising an 18% increase since 2017. Of these, 68 (15.9%) had attempted to wean off KDT but had to re-start as a result of a deterioration in seizures. CONCLUSIONS: The number of individuals following medical KDT remains stable. Referral numbers and waiting lists remain high, highlighting that KDT is still a well-recognised treatment option for drug-resistant epilepsy. The types of KDT used are similar to previous years, although increasingly flexible protocols are being adopted. Longer-term use of KDT is increasing, with a proportion of patients requiring long-term use to maintain seizure control.

The SLICE-3D dataset: 400,000 skin lesion image crops extracted from 3D TBP for skin cancer detection.

AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D ("Skin Lesion Image Crops Extracted from 3D TBP") dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection.

Diffuse Dermal Angiomatosis of the Breast.

Diffuse dermal angiomatosis (DDA) is a rare, benign cutaneous disorder that can affect the breasts. Typically, it presents in middle-aged women and is increasingly associated with various risk factors that involve tissue hypoxia. We report this case of classical bilateral DDA of the breasts in a 56-year-old female patient. This case highlights the association of DDA with hypoxia-inducing risk factors, such as smoking. Management of the hypoxic risk factors resulted in the resolution of the bilateral ulceration caused by DDA in this patient. This case report aims to discuss the etiology, risk factors, clinical manifestations, and treatment modalities commonly used to manage this condition.