Tumor progression upon treatment arises from preexisting resistant cancer cells and/or adaptation of persister cancer cells committing to an expansion phase. Here, we show that evasion from viral mimicry response allows the growth of taxane-resistant triple-negative breast cancer (TNBC). This is enabled by an epigenetic state adapted to taxane-induced metabolic stress, where DNA hypomethylation over loci enriched in transposable elements (TE) is compensated by large chromatin domains of H3K27me3 to warrant TE repression. This epigenetic state creates a vulnerability to epigenetic therapy against EZH2, the H3K27me3 methyltransferase, which alleviates TE repression in taxane-resistant TNBC, leading to double-stranded RNA production and growth inhibition through viral mimicry response. Collectively, our results illustrate how epigenetic states over TEs promote cancer progression under treatment and can inform about vulnerabilities to epigenetic therapy. SIGNIFICANCE: Drug-resistant cancer cells represent a major barrier to remission for patients with cancer. Here we show that drug-induced metabolic perturbation and epigenetic states enable evasion from the viral mimicry response induced by chemotherapy in TNBC. These epigenetic states define a vulnerability to epigenetic therapy using EZH2 inhibitors in taxane-resistant TNBC.

There is a lack of validated tools to measure fatigue in patients with inflammatory skin, neuropsychiatric, and medical disorders. The use of nonvalidated tools may compromise the quality of data. The purpose of this meta‐review was to evaluate existing fatigue scales commonly used to assess fatigue in other inflammatory conditions and to identify if there are scales that have been validated in dermatologic conditions. The PubMed/MEDLINE and SCOPUS databases were systematically searched from inception through March 10, 2020, in accordance with the PRISMA statement. Validated tools were identified and assessed according to their main measurement properties. The literature search identified 403 references, and eight studies were eligible and assessed in this review. The unidimensional fatigue scales included were the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT‐F), Brief Fatigue Inventory, Fatigue Severity Scale, Numerical Rating Scale – Fatigue, and Visual Analog Scale – Fatigue. The multidimensional fatigue scales found were the Checklist Individual Strength, Chalder Fatigue Scale, Multidimensional Assessment of Fatigue, Multidimensional Fatigue Inventory Scale, and Piper Fatigue Scale. To measure fatigue, a brief scale with the ability to detect change is needed as there is a growing interest in evaluating this dimension of treatment response. In addition, a good content validity is also needed. From this systematic review, none of the selected scales have had content validation, even though the FACIT was validated in patients with psoriatic arthritis. Validation studies in specific disorders are urgently warranted.

Sporotrichosis infections may cause cutaneous lesions mimicking other infectious or non-infectious causes such as pyoderma gangrenosum. We present a case of cutaneous sporotrichosis misdiagnosed as pyoderma gangrenosum and treated with immunosuppressants for 17 months leading to exacerbation and atypical morphology mimicking Histoplasma organisms on biopsy. Exclusion of infection prior to diagnosing pyoderma gangrenosum is important to prevent iatrogenic immunosuppression, demonstrating the challenges with application of the updated pyoderma gangrenosum diagnostic criteria.

ObjectiveTo evaluate the diagnostic accuracy of teleretinal screening compared with face-to-face examination for detection of diabetic retinopathy (DR) and age-related macular degeneration (AMD).Methods and analysisThis study adhered to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA). A comprehensive search of OVID MEDLINE, EMBASE and Cochrane CENTRAL was performed from January 2010 to July 2021. QUADAS-2 tool was used to assess methodological quality and applicability of the studies. A bivariate random effects model was used to perform the meta-analysis. Referrable DR was defined as any disease severity equal to or worse than moderate non-proliferative DR or diabetic macular oedema (DMO).Results28 articles were included. Teleretinal screening achieved a sensitivity of 0.91 (95% CI: 0.82 to 0.96) and specificity of 0.88 (0.74 to 0.95) for any DR (13 studies, n=7207, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) low). Accuracy for referrable DR (10 studies, n=6373, GRADE moderate) was lower with a sensitivity of 0.88 (0.81 to 0.93) and specificity of 0.86 (0.79 to 0.90). After exclusion of ungradable images, the specificity for referrable DR increased to 0.95 (0.90 to 0.98), while the sensitivity remained nearly unchanged at 0.85 (0.76 to 0.91). Teleretinal screening achieved a sensitivity of 0.71 (0.49 to 0.86) and specificity of 0.88 (0.85 to 0.90) for detection of AMD (three studies, n=697, GRADE low).ConclusionTeleretinal screening is highly accurate for detecting any DR and DR warranting referral. Data for AMD screening is promising but warrants further investigation.PROSPERO registration numberCRD42020191994.

Background: The prognosis of heart failure (HF) after early stage breast cancer (EBC) treatment with anthracyclines or trastuzumab is not well-characterized. Methods: Using administrative databases, women diagnosed with HF after receiving anthracyclines or trastuzumab for EBC in Ontario during 2007 to 2017 (the EBC-HF cohort) were categorized by cardiotoxic exposure (anthracycline alone, trastuzumab alone, sequential therapy with both agents) and matched on age with ≤3 cancer-free HF controls to compare baseline characteristics. To study prognosis after HF onset, we conducted a second match on age plus important HF prognostic factors. The cumulative incidence function was used to describe risk of hospitalization or emergency department visits (hospital presentations) for HF and cardiovascular death. Results: A total of 804 women with EBC developed HF after anthracyclines (n=312), trastuzumab (n=112), or sequential therapy (n=380); they had significantly fewer comorbidities than 2411 age-matched HF controls. After the second match, the anthracycline-HF cohort had a similar 5-year incidence of HF hospital presentations (16.5% [95% CI, 12.0%–21.7%]) as controls (17.1% [95% CI, 14.4%–20.1%]); the 5-year incidence was lower than matched controls for the trastuzumab-HF (9.7% [95% CI, 4.7%–16.9%]; controls 16.4% [95% CI, 12.1%–21.3%]; P =0.03) and sequential-HF cohorts (2.7% [95% CI, 1.4%–4.8%]; controls 10.8% [95% CI, 8.9%–13.0%]; P <0.001). At 5 years, the incidence of cardiovascular death was 2.9% (95% CI, 1.2%–5.9%) in the anthracycline-HF cohort vs. 9.5% (95% CI, 6.9%–12.6%) in controls, and 1.7% (0.6%–3.7%) for women developing HF after trastuzumab vs. 4.3% (95% CI, 3.1–5.8%) for controls. Conclusions: Women developing HF after cardiotoxic EBC chemotherapy have fewer comorbidities than cancer-free women with HF; trastuzumab-treated women who develop HF have better prognosis than matched HF controls.

Introduction Testing of 25-hydroxy (25-OH) vitamin D serum levels has increased drastically in recent years and much of it is considered inappropriate based on current guidelines. Methods In consultation with our physician groups (experts and frequent orderers), we modified existing guidelines and implemented a rational policy for 25-OH vitamin D testing and 1,25 dihydroxy (1,25 di-OH) vitamin D testing at a tertiary care centre. A computer decision support tool requiring selection of one of five acceptable testing indications was created for each test as part of a computerised physician order entry system. Results As a result of our intervention, we observed a 27% decrease in the average monthly test volume for 25-OH vitamin D from 504±62 (mean±SD) tests per month to 370±33 (p<0.001). 1,25 di-OH vitamin D testing decreased 58% from 71±18 to 30±10 (p<0.001). The departments ordering the tests were similar during the preintervention and postintervention periods, and further audits, patient chart reviews and individualised physician feedback were required to ensure appropriate ordering of 1,25 di-OH vitamin D. The most common ordering reasons selected were malabsorption/dietary concerns (46%) for 25-OH vitamin D and renal failure (42%) for 1,25 di-OH vitamin D. Conclusions Limitations of our computer decision support tool include a dependence on an honour system in selecting the testing indication and an inability to limit ordering frequency. Periodic monitoring of test volumes will be required to ensure adherence to guidelines. Despite these limitations, we have improved appropriate utilisation of these tests and reduced costs by approximately $C60 375 per year.

Treating actinic keratosis (AK) and photodamaged skin is critical to reduce the risk of progression to skin cancer. Laser resurfacing for AK treatment is available as either lesion-directed or field therapy. Laser resurfacing removes the superficial epidermis and dermis containing actinic damage, promoting re-epithelialization of healthy skin. Although laser resurfacing has been explored as a modality for AK treatment in the literature, studies summarizing its efficacy in the treatment of AK are lacking. This review summarizes existing research on laser resurfacing as a monotherapy for AK treatment, highlighting the various laser resurfacing modalities available for AK treatment as well as their complications and efficacy in comparison to other therapies. Despite longer healing time, fully ablative laser resurfacing, including carbon dioxide and erbium-doped yttrium aluminum garnet were found to be more effective for AK treatment than fractional ablative techniques. Although some studies suggest laser resurfacing monotherapy as less efficacious than photodynamic therapy, and equally effective to 5-fluorouracil and 30% trichloroacetic acid, clinical trials of larger sample size are required to establish stronger evidence-based conclusions. Moreover, laser resurfacing used as lesion-directed therapy, as opposed to the usual field-therapy, requires further investigation.

We present a case of malignant melanoma (MM) developing within a vascular malformation showing features of cellular blue nevi. A 47-year-old male presented with acute symptoms of a temporal and zygomatic mass, which were both previously asymptomatic upon development 30 years ago. These masses were diagnosed as vascular malformations upon imaging and were treated with sclerotherapy. Embolization and surgical excision were performed 3 years later due to symptomatic growth. Final pathology reports showed MM with congenital blue nevi. We hypothesize a possible linkage to a sporadic <i>KRAS</i> mutation, linking both presentations of vascular malformation, MM, and cellular blue nevi. A literature search for similar cases is also reported.