Explore the vast range of titles available.

Clearance of comedone is challenging in the treatment of acne, as it is very likely to develop into inflammatory lesions. However, there is lack of effective treatments for dense comedones. Comedone extractor has been widely employed by dermatologists, but the effect is temporary and may cause irritation. CO2 laser is a potential method for dense comedones, but the efficacy and safety need to be explored. In this single-center, randomized, single-blind, self-controlled study, the faces of patients with dense comedones were randomly assigned into two sides receiving either ultra-pulse dynamic CO2 laser or comedone extraction at an interval of 2 weeks for 4 sessions. After 4 treatments, the average comedone reduction rate of the CO2 laser was 64.49%, which was higher than that by the extractor (46.36%) (P < .001). 79.16% of the patients reached over 50% reduction by CO2 laser, while only 37.5% on extractor treated side reached 50% clearance. Texture index, porphyrin index, red zone, erythema index, and transepidermal water loss decreased after both treatments, and CO2 laser showed more improvement. There was no difference in hydration index and melanin index between the two treatments. No permanent or severe side effects were observed on both sides. The CO2 laser showed higher comedone clearance with lower pain scores than the comedone extractor.

Background:Oral isotretinoin is a commonly used treatment agent for acne vulgaris. In recent years, musculoskeletal side effects have become more common.Objectives:In this study, we aimed to share real life data about our patients who developed inflammatory low back pain due to isotretinoin use and presented to our rheumatology outpatient clinic.Methods:In this multicenter study, a total of 59 patients who developed inflammatory low back pain after isotretinoin use were included. Demographic, clinical and radiologic characteristics of the patients were obtained retrospectively from patient registration files. Approval for our study was obtained from the Ethics Committee of Firat University.Results:Of the patients included in the study, 47 (79.7%) were female and 12 (21.3%) were male. 55 (93.2%) patients used isotretinoin for acne vulgaris and 4 (6.8%) for comedones. The amount of isotretinoin use was 4693 mg (min:600 mg, max:10800 mg) and the duration of use was 5 months (±2.98). The mean follow-up period was 13.5 months. The complaints of 44 patients (76.3%) developed in the first three months. Pelvic radiographs of our patients showed grade 2 sacroilitis in 5 (8.5%) patients and grade 1 sacroilitis in 21 (35.6%) patients. Sacroiliac MRI revealed bilateral sacroilitis in 47 (79.7%) patients and unilateral sacroilitis in 10 (16.9%) patients. HLA-27 was negative in 43 (72.9%) patients, positive in 2 (3.4%) patients, and not analyzed in 14 (23.7%) patients. The mean baseline BASDAI score was 5.46 (±1.52) and the mean BASDAI score 3 months after discontinuation of NSAIDs and exercise was 2.46 (±1.90). 33 (55.9%) patients had normal follow-up MRI scans and 5 (8.5%) patients had chronic sacroilitis. During our follow-up, 5 patients were diagnosed with ankylosing spondylitis and 1 patient with SAPHO syndrome.Conclusion:Isotretinoin is an important treatment agent generally used for moderate to severe acne vulgaris. There are very few case-control reports of sacroilitis after isotretinoin use. In our study, patients with inflammatory low back pain and anamnesis of isotretinoin use were included and long-term results were shown. 6 patients were diagnosed with rheumatologic diseases in our follow-up and our study is important in this respect. In rheumatology practice, questioning isotretinoin use during history taking is important and should be taken into consideration. Large-scale studies with more cases are needed in this field.REFERENCES:NIL.Acknowledgements:Thank you to all authors.Disclosure of Interests:None declared.

Acne vulgaris is a common chronic skin disorder presenting with comedones, cystic structures forming within the distal hair follicle, and in most cases additionally with inflammatory skin lesions on the face and upper torso. We performed a genome-wide association study and meta-analysis of data from 34,422 individuals with acne and 364,991 controls from three independent European-ancestry cohorts. We replicated 19 previously implicated genome-wide significant risk loci and identified four novel loci [11q12.2 (FADS2), 12q21.1 (LGR5), 17q25.3 (FASN), and 22q12.1 (ZNRF3-KREMEN1)], bringing the total number of reported acne risk loci to 50. Our meta-analysis results explain 9.4% of the phenotypic variance of acne. A polygenic model of acne risk variants showed that individuals in the top 5% of the risk percentiles had a 1.62-fold (95% CI 1.47–1.78) increased acne risk relative to individuals with average risk (20–80% on the polygenic risk score distribution). Our findings highlight the Wnt and MAPK pathways as key factors in the genetic predisposition to acne vulgaris, together with the effects of genetic variation on the structure and maintenance of the hair follicle and pilosebaceous unit. Two novel loci, 11q12.2 and 17q25.3, contain genes encoding key enzymes involved in lipid biosynthesis pathways.

Acne vulgaris, one of the most common skin conditions, affects up to 85% of late adolescents, currently no universally accepted assessment system. The biomechanical properties of skin provide valuable information for the assessment and management of skin conditions. Wave-based optical coherence elastography (OCE) quantitatively assesses these properties of tissues by analyzing induced elastic wave velocities. However, velocity estimation methods require significant expertise and lengthy image processing times, limiting the clinical translation of OCE technology. Recent advances in machine learning offer promising solutions to simplify velocity estimation process. In this study, we proposed a novel end-to-end deep-learning model, named velocity prediction network (VP-Net), aiming to accurately predict elastic wave velocity from raw OCE data of in vivo healthy and abnormal human skin. A total of 16,424 raw phase slices from 1% to 5% agar-based tissue-mimicking phantoms, 28,270 slices from in vivo human skin sites including the palm, forearm, back of the hand from 16 participants, and 580 slices of facial closed comedones were acquired to train, validate, and test VP-Net. VP-Net demonstrated highly accurate velocity prediction performance compared to other deep-learning-based methods, as evidenced by small evaluation metrics. Furthermore, VP-Net exhibited low model complexity and parameter requirements, enabling end-to-end velocity prediction from a single raw phase slice in 1.32 ms, enhancing processing speed by a factor of ∼100 compared to a conventional wave velocity estimation method. Additionally, we employed gradient-weighted class activation maps to showcase VP-Net's proficiency in discerning wave propagation patterns from raw phase slices. VP-Net predicted wave velocities that were consistent with the ground truth velocities in agar phantom, two age groups (20s and 30s) of multiple human skin sites and closed comedones datasets. This study indicates that VP-Net could rapidly and accurately predict elastic wave velocities related to biomechanical properties of healthy and abnormal skin, offering potential clinical applications in characterizing skin aging, as well as assessing and managing the treatment of acne vulgaris.

BackgroundThe diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial.MethodsWe analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project.ResultsMicroinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0–25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P <  0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P <  0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005).ConclusionsThe higher breast cancer mortality with microinvasion indicates a more aggressive disease.

Background The immune microenvironment in ductal carcinoma in situ (DCIS) and its significance are not well established. This study was conducted to evaluate the immune microenvironment of DCIS including the composition of tumor-infiltrating lymphocyte (TIL) subsets and PD-L1+ immune cells and to compare it with that of invasive breast cancer. Materials and methods A total of 671 cases including three different disease groups of pure DCIS, DCIS with microinvasion (DCIS-M), and invasive carcinoma were included in this study. CD4+, CD8+, and FOXP3+ TIL subsets and PD-L1+ immune cells were detected with immunohistochemistry using tissue microarrays and were analyzed in relation to clinicopathologic characteristics and different disease groups. Results In pure DCIS, high infiltrations of CD4+, CD8+, and FOXP3+ T cells and the presence of PD-L1+ immune cells were associated with high nuclear grade, comedo-type necrosis, hormone receptor (HR) negativity, and high Ki-67 proliferation index. All immune cell infiltrations were higher in invasive carcinoma than in pure DCIS regardless of the HR status. While CD4+ T cells were more abundant than CD8+ T cells in pure DCIS, CD8+ T cells were dominant in invasive carcinoma, especially in HR-negative tumors. Within individual cases of invasive carcinoma with DCIS component, all immune cell subset infiltration was higher in the invasive component than in the DCIS component; however, CD4+ TIL infiltration did not differ between the two components in HR-negative tumors. Comparing pure DCIS, DCIS-M, and DCIS associated with invasive carcinoma (DCIS-INV), CD4+ TIL infiltration revealed a gradual increase from pure DCIS to DCIS-M and DCIS-INV in the HR-negative group, whereas FOXP3+ TIL infiltration was significantly increased in DCIS-INV than in pure DCIS in the HR-positive group. The high infiltration of FOXP3+ TIL and the presence of PD-L1+ immune cells were associated with tumor recurrence in patients with pure DCIS. Conclusions Our study showed that the immune microenvironment differs significantly not only between DCIS and invasive carcinoma but also between pure DCIS, DCIS-M, and DCIS-INV depending on the HR status.

Background It is difficult to preserve the structure and microbial distribution inside comedonal plugs during routine processing. Objective The objective of this study is to determine the optimal method to preserve the comedonal corneum plug structure and inherent microorganisms thereby eliminating the need to perform punch biopsies in relevant studies. Methods Corneum plugs were extracted from comedones of acne vulgaris patients. Primary embedding using either a 2% agarose, 2% agar, 25% gelatin, or 2% agar + 2.5% gelatin solution was subsequently performed and the results compared. The specimens were then fixed, waxed, sectioned, and examined by light, fluorescence, and scanning electron microscopies to observe the structures and microorganisms within the plugs. Results Both the 25% gelatin and 2% agarose solutions successfully preserved the structural integrity of corneum plugs and the inherent microorganisms. When considering other factors such as thermostability, reusability, and convenience, the 25% gelatin solution was the superior choice among the four materials. Conclusion We report a simple and effective method for double embedding comedonal plugs and other small tissue specimens. The technique preserves the structure and microbial distribution in situ within comedonal corneum plugs, eliminates the need for punch biopsies. This method may also be applied to other tiny and fragile tissue specimens, thereby enabling a potentially wide array of future large‐scale investigations and alleviated patients’ pain.

Tumor-infiltrating lymphocytes (TILs) provide prognostic value in invasive breast cancer and guidelines for their assessment have been published. This study aims to evaluate: (a) methods of TILs assessment, and (b) their prognostic significance in breast ductal carcinoma in situ (DCIS). Hematoxylin and eosin sections from two clinically annotated DCIS cohorts; a training set ( n  = 150 pure DCIS) and a validation set ( n  = 666 comprising 534 pure DCIS and 132 cases wherein DCIS and invasive breast carcinoma were co-existent) were assessed. Seven different scoring methods were applied to the training set to identify the most optimal reproducible method associated with strongest prognostic value. Among different methods, TILs touching ducts’ basement membrane or away from it by one lymphocyte cell thickness provided the strongest significant association with outcome and highest concordance rate [inter-cluster correlation coefficient = 0.95]. Assessment of periductal TILs at increasing distances from DCIS (0.2 , 0.5 , and 1 mm) as well as percent of stromal TILs were practically challenging and showed lower concordance rates than touching TILs. TILs hotspots and lymphoid follicles did not show prognostic significance. Within the pure DCIS validation set, dense TILs were associated with younger age, symptomatic presentation, larger size, higher nuclear grade, comedo necrosis and estrogen receptor negativity as well as shorter recurrence-free interval ( p  = 0.002). In multivariate survival analysis, dense TILs were independent predictor of shorter recurrence-free interval ( p  = 0.002) in patients treated with breast conservation. DCIS associated with invasive carcinoma showed denser TILs than pure DCIS ( p  = 9.0 × 10 −13 ). Dense TILs is an independent prognostic variable in DCIS. Touching TILs provides a reproducible method for their assessment that can potentially be used to guide management

[...]CLIN/ADAP was also effective in reducing lesions (RR = 4.36, 95% CI [2.62 to 7.27], P < 0.00001), but it was associated with a higher incidence of adverse events. Summary of the included studies Study ID Country Study design Total Participants Follow up duration Main inclusion criteria Primary outcomes Conclusion LS Gold, 2021 [3] USA and Canada phase II, randomized, double-blind, parallel-group, vehicle-controlled study 35 centres 741 12 weeks participants aged ≥ 9 years with moderate-to-severe acne Treatment success rates and lesion reductions were significantly greater with IDP-126 than with vehicle Once-daily treatment with the novel fixed-dose triple-combination gel has superior efficacy to vehicle and all three dyad component gels LS Gold, study 1 2023 [4] North America phase 3, randomized, double-blind, parallel-group, vehicle-controlled study. 15 centres 183 12 weeks participants had to have the following facial lesions: ≥30 to ≤ 100 inflammatory (papules/pustules/nodules), ≥ 35 to ≤ 150 noninflammatory (closed/open comedones), and ≤ 2 nodules Treatment success-Inflammatory lesions-Noninflammatory lesions were significantly greater with IDP-126 thank with vehicle or any of the dyad combinations The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in participants with moderate-to-severe acne LS Gold, Study 2 2023 [4] North America phase 3, randomized, double-blind, parallel-group, vehicle-controlled study. 15 centres 180 12 weeks participants had to have the following facial lesions: ≥30 to ≤ 100 inflammatory (papules/pustules/nodules), ≥ 35 to ≤ 150 noninflammatory (closed/open comedones), and ≤ 2 nodules Treatment success-Inflammatory lesions-Noninflammatory lesions were significantly greater with IDP-126 than vehicle or any of the dyad combinations The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in participants with moderate-to-severe acne LF Eichenfield,2023 [5] USA and Canada phase II, randomized, double-blind, parallel group, vehicle-controlled study. 35 centres 394 12 weeks Participants ranging from 10 to 17 years with moderate-to-severe acne TTreatment success rates and lesion reductions were significantly greater with IDP-126 than with vehicle IDP-126 gel a novel fixed-dose, triple-combination topical formulation for acne demonstrated superior efficacy to vehicle and three dyad component gels [See PDF for image] Fig. 1 A: A forest plot showing the incidence of adverse events of CLIN/ADAP compared to the vehicle Author contributions Conceptualization and design of the work: [AE, MA]; Acquisition of the data: [MA, MK, DH, NC and AE]; Formal analysis: [AE]; Interpretation of data: [AE, MA, AE]; Drafting the work: [all authors]; Revising the work critically: [MA, AE, SC, NC]; Final approval of the version to be published and agreement to be accountable for all aspects of the work: [all authors] Funding No funding was received for conducting this study.

BackgroundExtracellular matrix (ECM) plays a crucial role in tumour behaviour. Prolyl-4-hydroxlase-A2 (P4HA2) is a key enzyme in ECM remodelling. This study aims to evaluate the prognostic significance of P4HA2 in breast ductal carcinoma in situ (DCIS).MethodsP4HA2 expression was assessed immunohistochemically in malignant cells and surrounding stroma of a large DCIS cohort comprising 481 pure DCIS and 196 mixed DCIS and invasive carcinomas. Outcome analysis was evaluated using local recurrence free interval (LRFI).ResultsHigh P4HA2 expression was detected in malignant cells of half of pure DCIS whereas its expression in stroma was seen in 25% of cases. Higher P4HA2 expression was observed in mixed DCIS cases compared to pure DCIS both in tumour cells and in stroma. High P4HA2 was associated with features of high risk DCIS including younger age, higher grade, comedo necrosis, triple negative and HER2-positive phenotypes. Interaction between P4HA2 and radiotherapy was also observed regarding the outcome. High P4HA2 expression was an independent prognostic factor in predicting shorter LRFI.ConclusionP4HA2 plays a role in DCIS progression and can potentially be used to predict DCIS outcome. Incorporation of P4HA2 with other clinicopathological parameters could refine DCIS risk stratification that can potentially guide management decisions.