Hot spots for clinical signs of disease activity in vitiligo.

There is evidence of a link between disease activity in vitiligo and clinical visible signs such as confetti-like depigmentation, Koebner phenomenon and hypochromic areas/borders. Despite its established value, dermatologists and researchers continue to have a limited understanding of the vitiligo disease activity signs. The primary goal of this study was to identify 'hot spots' of disease activity signs in vitiligo patients in order to improve detection in clinical practice. Furthermore, the prevalence, clinical profiles of predisposed patients, interrelationship between the disease activity signs and potential pitfalls in the recognition of the signs were evaluated. The Vitiligo Signs of Activity Score (VSAS) was used to score the presence of the disease activity signs in 441 non-segmental and 57 segmental vitiligo patients. More detailed predilection areas were scored in a subset of patients, using 65 predefined body locations. At least one disease activity sign was observed in 51.0% and 8.8% of the non-segmental and segmental vitiligo patients, respectively. Confetti-like depigmentation was most observed on the elbows, Koebner phenomenon on the back of the hands, and hypochromic areas/borders in the armpits. The three signs were significantly more observed in patients with more involved body locations. Moreover, hypochromic areas/borders were more common in younger patients. Confetti-like depigmentation had the highest interrelationship with the other signs and was the easiest to recognise. Knowledge around hot spots of the disease activity signs will enhance and simplify their detection in clinical practice. Based on the results, confetti-like depigmentation appears to be the most straightforward sign to evaluate.

Clinician-reported outcome measures for the assessment of vitiligo: A scoping review.

Clinician-reported outcome measures (ClinROMs) are essential for assessment of vitiligo in clinical trials and daily practice. Several instruments have been developed and tested to measure, for example, vitiligo extent, repigmentation and activity. The goal of this review was to identify all introductory publications of ClinROMs for vitiligo that include at least some aspects of validation and to describe the instruments' characteristics, intention for use and practical strengths and limitations. A search strategy was conducted in PubMed, Embase and Cochrane Library (CENTRAL) from inception to July 2022. Based on the literature search (n = 2860), 10 articles were identified, describing 14 different ClinROMs. Six ClinRoms measured disease extent and/or repigmentation, seven evaluated disease activity and one was a composite score. The Vitiligo Area Scoring Index (VASI), and Vitiligo Extent Score (VES and VESplus) measure overall disease extent and/or repigmentation. The VASI relies on hand units (1% body surface area), whereas the VES and VESplus use a picture-based scoring technique. The Vitiligo Extent Score for a Target Area (VESTA) measures repigmentation percentage for target lesions. One global assessment score for extent has been validated. Vitiligo disease activity scores included a static measure of clinical activity signs (Vitiligo Signs of Activity Score [VSAS]) and two measures assessing dynamic evolution (Vitiligo Disease Activity Score [VDAS] and Vitiligo Disease Improvement Score [VDIS]). The Vitiligo European Task Force assessment tool (VETFa) is a composite score. Depending on the practical strengths and limitations as well as the research question and setting (clinical trials vs. daily practice), the choice of an appropriate ClinROM may differ. Fourteen ClinROMs in vitiligo were identified to measure vitiligo extent, repigmentation, and activity. Further research evaluating the validity, reliability, and responsiveness of each instrument and worldwide consensus on which instrument to use for a specific outcome (domain) is greatly needed.

Evaluation of the Effects of Microgravity on Activated Primary Human Hepatic Stellate Cells.

In recent years, research has been conducted to develop new medical treatments by simulating environments existing in space, such as zero-gravity. In this study, we evaluated the cell proliferation and gene expression of activated primary human hepatic stellate cells (HHSteCs) under simulated microgravity (SMG). Under SMG, cell proliferation was slower than in 1 G, and the evaluation of gene expression changes on day 1 of SMG by serial analysis of gene expression revealed the presence of Sirtuin, EIF2 signaling, hippo signaling, and epithelial adherence junction signaling. Moreover, reactive oxygen species were upregulated under SMG, and when N-acetyl-cystein was added, no difference in proliferation between SMG and 1 G was observed, suggesting that the oxidative stress generated by mitochondrial dysfunction caused a decrease in proliferation. Upstream regulators such as smad3, NFkB, and FN were activated, and cell-permeable inhibitors such as Ly294002 and U0126 were inhibited. Immunohistochemistry performed to evaluate cytoskeletal changes showed that more ß-actin was localized in the cortical layer under SMG.

An uncommon presentation of a cutaneous angiosarcoma.

Cutaneous angiosarcoma (cAS) is a rare and aggressive malignant vascular tumor, which mostly occurs in the head and neck region. The outcome of cAS is poor and timely diagnosis is paramount, but often delayed because of the slow onset and the variance in presentation. This paper reports on a case of an 88-year old woman who presented with a persisting "hematoma" in the left retro-auricular region. Although considered at initial differential diagnosis, no signs of malignancy were identified in histopathology and imaging in the diagnostic work-up. At first, short-term follow-up showed no progression of the lesion. But 3 months after the first presentation additional biopsies were taken, because of rapid expansion of the lesion. The initial histopathological findings were most consistent with a benign vascular lesion, with signs of hemorrhage and reactive inflammation. However, the additional immunohistochemical analysis showed the presence of MYC oncoprotein, which confirmed the clinical suspicion of angiosarcoma. Because size and location of the lesion rendered complete resection unattainable, radiotherapy was commenced, but no significant volume reduction could be achieved. Therefore, palliative irradiation was initiated. The patient passed away 1 month later. Clinical diagnosis is often difficult and little is known about imaging of cAS. Histology and immunohistochemistry can be misleading, as cAS are easily mistaken for other lesions. Most studies report that multimodality treatment with surgery and radiotherapy is preferable, but this can be challenging in the head & neck region.

Long-term outcome after the ross procedure in 173 adults with up to 25 years of follow-up.

OBJECTIVES: The potential risk of autograft dilatation and homograft stenosis after the Ross procedure mandates lifelong follow-up. This retrospective cohort study aimed to determine long-term outcome of the Ross procedure, investigating autograft and homograft failure patterns leading to reintervention. METHODS: All adults who underwent the Ross procedure between 1991-2018 at the University Hospitals Leuven were included, with follow-up data collected retrospectively. Autograft implantation was performed using the full root replacement technique. The primary end-point was long-term survival. Secondary end-points were survival free from any reintervention, autograft or homograft reintervention-free survival, and evolution of autograft diameter, homograft gradient and aortic regurgitation grade over time. RESULTS: A total of 173 adult patients (66% male) with a median age of 32 years (range 18-58 years) were included. External support at both the annulus and sinotubular junction was used in 38.7% (67/173). Median follow-up duration was 11.1 years (IQR, 6.4-15.9; 2065 patient-years) with 95% follow-up completeness. There was one (0.6%) perioperative death. Kaplan-Meier estimate for 15-year survival was 91.1% and Ross-related reinterventionfree survival was 75.7% (autograft: 83.5%, homograft: 85%). Regression analyses demonstrated progressive neoaortic root dilatation (0.56 mm/year) and increase in homograft gradient (0.72 mmHg/year). CONCLUSIONS: The Ross procedure has the potential to offer excellent long-term survival and reintervention-free survival. These long-term data further confirm that the Ross procedure is a suitable option in young adults with aortic valve disease which should be considered on an individual basis.

Image analysis systems to calculate the surface area of vitiligo lesions: A systematic review of measurement properties.

Several digital image analysis systems have been developed for surface calculation of vitiligo lesions. Critical assessment of their measurement properties is crucial to support evidence-based recommendations on the most suitable instruments and will reveal the need for future research. A systematic review was performed to systematically summarize, compare, and critically assess the measurement properties of digital and analogue analysis systems for surface calculation of vitiligo lesions following the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. Nineteen clinical trials were selected including 25 different instruments. Manual tracing on transparent sheets (contact planimetry) combined with digital measurement or point counting can be considered as the best validated method for the evaluation of target lesions taking into account the skin curvatures. Two-dimensional digital imaging analysis on photographs seems also robust although confirmatory data of different research groups using the same digital instrument in a wide range of skin types are missing. Analysis based on 3D photography is still in its early stage but is promising for whole-body analysis. However, the reported data on the quality of the instruments for surface area calculation of vitiligo lesions were in general rather limited. Therefore, future high-quality validation studies are required also including full body evaluations.

Evolving therapies for Peyronie's disease: how can we work towards new drugs?

Peyronie's disease (PD) is an idiopathic chronic fibrotic disease that causes a penile curvature (PC), subsequent erectile dysfunction (ED) and impaired sexual intercourse in patients. As of yet, there are no reliable non-surgical treatment options available. Intralesional injection with collagenase Clostridum Histolyticum has been FDA approved since 2013, but post-approval studies have not been unanimously positive. Moreover, it renders a curvature improvement of only 30% on average, usually still requiring surgical intervention to remedy PC. Therefore, there is a need for drugs which could prevent surgery altogether. Development of new drugs can either be through a target-based or phenotypic assay-based approach. The current in vivo model for PD is dependent on treatment of primary PD-derived fibroblasts with transforming growth factor-ß1. Moreover, despite the existence of a genetic in vivo PD model, it does not allow for drug screening or testing. While some advances have been made in the past few years, new in vivo and in vivo systems and well-designed studies are urgently needed for the non-surgical treatment of PD.

Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction.

INTRODUCTION: Previous research in the field of cardiovascular diseases suggests a relaxing effect of testosterone (T) on smooth muscle cells. Therefore, it was hypothesized that T could play a significant role in erection development. AIM: To investigate the relaxing effect of T and other molecules of the T signaling pathway on human corpus cavernosum (HCC) tissue. METHODS: Samples of the HCC tissue were obtained from men who underwent penile prosthesis implantation (n = 33) for erectile dysfunction. Samples were used for isometric tension measurement in Ex Vivo experiments. Following standardized precontraction with phenylephrine, increasing doses of T or dihydrotestosterone were administered and blocked by NO/H2S synthesis inhibitors, a KATP blocker, and flutamide (androgen receptor inhibitor). MAIN OUTCOME MEASURE: The outcome was relaxation of the HCC tissue, normalized to a maximum precontraction achieved by phenylephrine. RESULTS: A dose-dependent relaxing effect of dihydrotestosterone and T was observed with a relaxation of, respectively, 24.9% ± 23.4% (P < .0001) and 41.7% ± 19.1% (P = .01) compared with 6.8% ± 15.9% for vehicle (dimethylsulfoxide) at 300 µM. The relaxing effect of T was not countered by blocking NO synthesis, H2S synthesis, KATP channels, or the androgen receptor. CLINICAL IMPLICATIONS: By understanding the underlying mechanisms of T-induced HCC relaxation, potential new therapeutic targets can be identified. STRENGTHS & LIMITATIONS: The strength of the study is the use of fresh HCC tissues with reproducible results. The limitation is the need for supraphysiological T levels to induce the observed effect. CONCLUSION: Rapid androgen-induced relaxation of HCC is likely to occur via nongenomic mechanisms. Previously suggested mechanisms of action by which T modulates HCC relaxation have been excluded. Van den Broeck T, Soebadi MA, Falter A, et al. Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction. J Sex Med 2019; 8:114-119.

Prognostic value of the high-sensitivity troponin T assay after percutaneous intervention of chronic total occlusions.

AIMS: The prognostic value of postprocedural high-sensitivity troponin T (hs-TnT) after percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) is currently unclear. We aimed to assess the prognostic value of elevated hs-TnT after elective CTO-PCI. METHODS: The current study included 409 patients undergoing elective CTO-PCI between September 2011 and August 2016 at two centres who had postprocedural hs-TnT measurements available. Clinical, angiographic and procedural characteristics were correlated with any or at least five times the 99th percentile hs-TnT elevation, as well as a 1-year combined endpoint of major adverse cardiac and cerebrovascular events (MACCE) and mortality. RESULTS: Post-CTO-PCI hs-TnT elevation was observed in 85% (n = 349/409) and at least five times hs-TnT elevation occurred in 42% (n = 172/409) of cases. hs-TnT elevation was more frequent in more complex patients (postcoronary artery bypass grafting, peripheral vascular disease, chronic kidney disease, heart failure and multivessel disease) as well as in the more complex CTO procedures (higher Japanese CTO complexity, use of retrograde and antegrade dissection re-entry techniques). After 1 year of follow-up (FU), MACCE was not associated with postprocedural hs-TnT elevation, both any elevation (10.9 vs. 11.7%; P = 0.846) and at least five times hs-TnT elevation (15.7 vs. 11.7%; P = 0.451; hazard ratio = 1.375, confidence interval: 0.599-3.157, P = 0.453), compared with no elevation. A nonsignificant trend towards higher mortality in the at least five times hs-TnT vs. no elevation group (4.7 vs. 0%; P = 0.091) was observed. CONCLUSION: In patients undergoing CTO-PCI, postprocedural hs-TnT elevation is frequent, but is not correlated with higher MACCE and mortality rates after 1-year FU in our small study population, suggestive of the limited long-term impact of troponin elevation.

Outcomes of the amphilimus-eluting polymer-free stent for chronic total occlusion treatment: a multicentre experience.

AIMS: Late stent thrombosis and delayed vessel wall healing remain an important issue in coronary vessels treated with drug-eluting stents (DES), especially when long-vessel segments need to be covered, like in chronic total occlusions (CTO). Avoiding polymer use to avoid chronic inflammatory responses is a potential solution to reduce target vessel failure (TVF). We aimed to validate the clinical safety and efficacy at 1 year of the polymer-free Cre8 DES vs. nonpolymer-free DES for the percutaneous treatment of CTO. METHODS: Between September 2011 and August 2016, patients were prospectively enrolled in three CTO centres. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), including cardiac death, any myocardial infarction, stent thrombosis, TVF and target vessel revascularization. RESULTS: A total of 102 Cre8 and 133 non-Cre8 patients were enrolled. At 1 year, a low cumulative MACCE was observed in the Cre8 group (6.9%, respectively). Moreover, a numerical trend towards better MACCE was observed in the Cre8 group vs. the non-Cre8 group (6.9 vs. 14.3%; P = 0.065). The clinically driven TVF rate was not statistically different between Cre8 and non-Cre8 patients (6.9 vs. 9.8%; P = 0.373). A borderline significant difference regarding mortality was observed in favour of Cre8 patients (0 vs. 3.8%; P = 0.049). CONCLUSION: Low rates of MACCE and TVF up to 1 year were observed in the Cre8 group, supportive of the use of polymer-free DES for lesions with high complexity.