Effectiveness and Drug Survival of Ixekizumab and Secukinumab in Patients with Moderate to Severe Plaque Psoriasis: Real-World Data from Bucharest, Romania.

Purpose: Multiple biological therapies have been developed for the treatment of inflammatory diseases, including moderate to severe plaque psoriasis. Choosing the optimal treatment for psoriasis can depend on several factors and is strongly influenced by a drug's efficacy and safety profile. Continuous treatment with biological therapies is recommended to achieve effective disease management in patients with psoriasis. However, in real-world, patients often discontinue biologic therapy within the first year of treatment. Therefore, in this study, we aimed to investigate the effectiveness and drug survival of two anti-interleukin 17 agents (ixekizumab and secukinumab) in a group of adult patients with moderate to severe psoriasis from Bucharest, Romania. Patients and Methods: We designed an observational, non-interventional, retrospective study of 255 adult patients with moderate to severe psoriasis receiving ixekizumab and secukinumab. We performed descriptive statistics and inferential methods, such as z-test, median test and Kaplan Meier curve comparison, to characterize the groups with two biological treatments. Results: Patients treated with ixekizumab had a longer drug survival compared to those treated with secukinumab with lower risks of non-persistence, discontinuation and switching therapy. Patients age-groups and psoriasis durations found to be significant factors in drug survival. Conclusion: This study contributes to the understanding of the drug survival profile and the factors that may influence it in ixekizumab and secukinumab treatment in a real-world setting.

Measurement of skin viscoelasticity: A non-invasive approach in allergic contact dermatitis.

Non-invasive bioengineering technologies are constantly being developed, as they can provide useful insights and contribute to the improvement of medical care and scientific education. The purpose of this study was to assess skin viscoelasticity using the suction chamber method in patients with allergic contact dermatitis vs. healthy subjects, before and after applying a moisturizer safety testing cream. This was a prospective controlled study over a 3-year period (March 2016-March 2019), with 81 subjects being divided in two balanced groups: Patients with allergic contact dermatitis and healthy subjects, respectively. The skin viscoelasticity was determined for all subjects with Cutometer®, using the suction method, by performing a dynamic assessment of parameters before and after applying a moisturizing cream. The results indicate a decrease in the elasticity parameters in both groups, indicating an improvement of the elastic properties under the treatment. Skin capacity to return to its previous form after the deformation, i.e., pure elasticity and biological elasticity, showed overall elevated values in the group with contact dermatitis, demonstrating the efficacy of the emollient cream after applying it for 28 days (increase by 11.7 and 4.9% respectively, compared with baseline, when patients had dry, untreated skin). However, in healthy subjects, these parameters do not achieve important values, but they remain rather stable over time with a very slight improvement (6.6% after 28 days). The Cutometer is an easy to use, efficient and widely used instrument for measurements in studies that perform a quantitative assessment of the effectiveness of different formulations intended for application on the skin.

Successful multidisciplinary clinical approach and molecular characterization by whole transcriptome sequencing of a cardiac myxofibrosarcoma: A case report.

BACKGROUND: Cardiac tumors are rare and complex entities. Surgery represents the cornerstone of therapy, while the role of adjuvant treatment remains unclear and, in case of relapse or metastatic disease, the prognosis is very poor. Lack of prospective, randomized clinical trials hinders the generation of high level evidence for the optimal diagnostic workup and multimodal treatment of cardiac sarcomas. Herein, we describe the multidisciplinary clinical management and molecular characterization of a rare case of cardiac myxofibrosarcoma in an elderly woman. CASE SUMMARY: A 73-year-old woman presented signs and symptoms of acute left-sided heart failure. Imaging examination revealed a large, left atrial mass. With suspicion of a myxoma, she underwent surgery, and symptoms were promptly relieved. Histology showed a cardiac myxofibrosarcoma, a rare histotype of cardiac sarcoma. Eight months later, disease unfortunately relapsed, and after a multidisciplinary discussion, a chemotherapy with doxorubicin and then gemcitabine was started, achieving partial radiologic and complete metabolic response, which was maintained up to 2 years and is still present. This report is focused on the entire clinical path of our patient from diagnosis to follow-up, through surgery and strategies adopted at relapse. Moreover, due to their rarity, very little is known about the molecular landscape of myxofibrosarcomas. Thus, we also performed and described preliminary genome analysis of the tumor tissue to get further insight on mechanisms involved in tumor growth, and to possibly unveil new clinically actionable targets. CONCLUSION: We report a case of cardiac myxofibrosarcoma that achieved a very good prognosis due to an integrated surgical, cardiac and oncologic treatment strategy.

Long-term Outcomes of Paediatric Patients Admitted With Acute Severe Colitis- A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN.

BACKGROUND AND AIM: Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. METHODS: This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. RESULTS: Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. CONCLUSIONS: High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.

Treat-to-target in Crohn's disease: Will transmural healing become a therapeutic endpoint?

Crohn's disease (CD) represents a chronic transmural inflammatory condition of the gastrointestinal tract, which usually leads to structural damage and significant disability. Deep remission - defined by both clinical and endoscopic remission, signifying mucosal healing - represents the current endpoint in the treat-to-target strategy, significantly improving patients' long-term outcomes. Transmural healing (TH) could be a more effective target, but this possibility remains unclear. This narrative review aims to critically review and summarize the available literature relating TH to long-term outcomes, being the first of its kind and to the best of the author's knowledge. A systematic literature search (from inception to March 31 2018) was performed, using multiple databases, and identifying seven full-text manuscripts. In those studies, long-term favorable outcomes (≥ 52 wk) included sustained clinical remission, as well as fewer therapeutic changes, CD-related hospitalizations, and surgeries. Despite heterogeneous design and methodological limitations, six of the studies demonstrated that TH or intestinal healing (TH plus mucosal healing) were predictive for the aforementioned favorable outcomes. Therefore, TH may become a reasonable therapeutic target and be included in the concept of deep remission. Further prospective, well-designed, multicenter trials aiming to better define the role of TH in personalized therapy for CD and to determine the long-term influence of TH on bowel damage and disability are warranted.

Role of In Vivo Reflectance Confocal Microscopy in the Analysis of Melanocytic Lesions.

Worldwide melanoma incidence and mortality are increasing (1). Despite the ongoing research, advanced melanoma is still incurable; therefore, the most appropriate solution seems to be early detection combined with complete surgical excision (2). Since the diagnostic protocol of suspicious lesions includes a complete excision with safety margins (2), the problem of unnecessary scarring is significant. The real challenge in this case is to have a properly formulated diagnosis before acquiring a biopsy. Currently available non-invasive techniques are coherence tomography, digital dermoscopy, and reflectance confocal microscopy. All these techniques allow for a presumptive diagnosis, but the most promising results are provided by reflectance confocal microscopy. Reflectance confocal microscopy (RCM) is an optical imaging technique that uses a laser diode as a source of coherent monochromatic light which penetrates the tissue and illuminates a single point. Light from the stimulated section is reflected and passes through a filter, thereby forming the image on the detector. This filter enables selective excitation of a particular point on which focus is achieved and rejects reflection from the out-of-focus area, thus obtaining a "confocal" image. Contrast is the result of differences in the refractive index of the cell organelles and microstructures, resulting in white structures on a black background. This technique allows, as opposed to conventional light microscopy, the analysis of sections obtained at a bi- or tri-dimensional level and controlling the depth of the field, permitting out-of-focus artifacts to be eliminated. In dermatology, this technique is useful for both clinical and research purposes. It is the only technique that allows horizontal viewing of the skin up to the superficial dermis (approximately 300 mm, at a cellular level resolution (0.5-1.0 µm in the lateral dimension and 4.0-5.0 µm in the axial dimension) (3). It allows both in vivo and ex vivo diagnosis, while providing the possibility for long-term monitoring. It has proved to be especially valuable for in vivo examinations of melanocytic lesions, whereas melanin and melanosomes are a powerful source of contrast, allowing the individualization of melanocytic cells (4). We report the case of a 65-year-old Caucasian woman who presented to the Dermatology Department of University of Modena and Reggio Emilia, Italy, for the examination of an atypical lesion, of unknown history, localized in the right preauricular area. The patient's personal and family histories were negative for skin malignancies and for other significant medical history. The clinical presentation was highly indicative of malignancy, as it met all the ABCD clinical criteria: an asymmetric papule composed of two areas, one pigmented and another one hypopigmented, with ill-defined borders and a diameter of approximately 2 cm. The dermatoscopic examination revealed an asymmetric multicomponent pattern with atypical network, structureless areas, peripheral irregular globules, and a blue-white veil. Because clinical and dermatoscopic features pointed towards a suspicious lesion which was situated on the face, where unnecessary scarring is unwanted, reflectance confocal microscopy (RCM) examination was proposed and performed (VivaScope 3000; MAVIG GmBH, Munich, Germany) (5). It revealed the following features: the epidermis presented a disarranged pattern; the dermo-epidermal junction and superficial dermis presented a meshwork pattern with edged AND non-edged papillae, non-homogenous junctional clusters, dense nests, dense AND sparse nests, and atypical cells in a sparse distribution (Figure 1). Figure 1. (A) Clinical examination of an atypical melanocytic lesion situated at the right preauricular area. (B) Dermatoscopic examination. (C) Confocal examination of dermo-epidermal junction and superficial dermis which reveals a meshwork pattern (yellow circle) with edged AND non-edged papillae, non-homogenous junctional clusters (yellow star), dense nests, dense AND sparse nests (red star) and atypical cells in a sparse distribution (arrow). The clinical and confocal data indicated a malignant melanocytic tumor, so an excisional biopsy with safety margins was performed. The histopathological report indicated superficial spreading melanoma with a Breslow of 0.55 mm and 0 mitosis/mm2. This case illustrates the important role confocal microscopy examination has in the management of melanocytic lesions situated in special areas like the face. Reflectance confocal microscopy is an imaging technique that allows viewing the layers of the skin up to the superficial dermis and therefore turns out to be extremely useful in obtaining a pertinent diagnosis before acquiring a biopsy. According to the data available so far, it was established that reflectance confocal microscopy increases the diagnostic accuracy for melanocytic lesions in both pigmented and hypopigmented lesions. In a study conducted by Borsari et al., reflectance confocal microscopy proved to have a sensibility and specificity of 95.3% and 83.9%, respectively (6). By improving the accuracy of clinical and dermatoscopic diagnosis, the reflectance confocal microscopy technique contributes to increasing the confidence of the clinical and dermatoscopic diagnosis (7). In this regard, confocal reflectance microscopy reduces unnecessary excisions, particularly in cases of damage to cosmetically important areas, such as the face or the neck, simultaneously detecting the malignant lesions that require a surgical approach, as seen in the case presented, where confirmation of the diagnosis by confocal microscopy allowed for a safe excision. In fact, the head and neck are the most appropriate body location for reflectance confocal examination, especially because RCM showed a high diagnostic accuracy for lesions located on sun-damaged skin, as these two areas frequently are (adjusted odds ratio (aOR), 2.13; 95% confidence interval (CI), 1.37-3.30; P=.001) (6). Reflectance confocal microscopy is very helpful in the management of special lesions, like facial lentigo maligna melanoma. This type of lesion is considered to be a real challenge for the dermatologist because of its clinical and morphological features that are similar to other lesions such as solar lentigines and pigmented actinic keratoses. In this case, reflectance confocal excels at specificity of the diagnosis, but also at to the ability to define the margins more accurately, permitting a pre-surgical mapping and for possibility of identifying the optimal site for biopsy (8,9). By improving diagnostic ability, reflectance confocal microscopy technique may contribute to the selection of lesions that may be eligible for non-surgical treatment. Facial pigmented non-melanocytic macules like solar lentigo, flat seborrheic keratosis, lichen planus-like keratosis, and pigmented actinic keratosis can mimic a lentigo maligna, or even a lentigo maligna melanoma, but with the help of the RCM, an accurate diagnosis can be established, sparing the patient can be from unwanted facial scars using a non-surgical approach (laser, cryotherapy, imiquimod) (10,11). Furthermore, reflectance confocal microscopy can be a valuable method for the monitoring of a skin lesion over time, especially melanocytic nevi, reducing unnecessary surgical excision, such as for patients with multiple atypical nevi that undergo multiple biopsies (12,13). Like all other diagnostic methods, RCM has its limitations: palmoplantar lesions (due to thickened epidermis), ulcers or crusts on a large lesion, lesions localized in inaccessible regions such as interdigital space, nasal wing (3). To summarize, reflectance confocal microscopy can improve clinical and dermatoscopic diagnosis of melanocytic lesions, detecting the lesions that need an invasive approach and preventing unnecessary excision. It has proven to be very helpful in the management of lentigo maligna and lentigo maligna melanoma, achieving high specificity in the diagnosis and simultaneously allowing an optimal approach. This technique can be a reliable bridge between dermoscopy and histopathology, being able to provide an alternative to histopathological examination. Special mention must be made of the factors that may change the result to a false negative such as hyperkeratosis, ulceration, or bleeding, so any results should be integrated with the rest of the patient's data.

Perianal infectious dermatitis: An underdiagnosed, unremitting and stubborn condition.

Perianal infectious dermatitis (PID) represents a superficial inflammation of the perianal skin, which is of bacterial origin (classically, group A beta-hemolytic streptococci). This narrative review aims to critically review and summarize the available scientific literature regarding pediatric PID, being the first of its kind, to the best of the author's knowledge. It also reports the first cases of Romanian children with PID. Multiple databases were subjected to systematic literature search (from 1966 to April 30, 2018) to identify studies and case reports of children with PID. As such, this review provides updated information about essential aspects of PID (epidemiology, etiology, pathogenesis, as well as clinical features, required investigations and therapeutic options) and of diagnostic pitfalls. Although a well-defined entity, PID remains largely underdiagnosed. PID may mimic other common conditions with skin manifestations (like candidiasis, pinworms, eczema, irritant dermatitis, anal fissure, hemorrhoids, Crohn's disease, psoriasis, seborrheic dermatitis, zinc deficiency dermatosis and even sexual abuse), with consequent unnecessary, sometimes expensive and invasive investigations and futile therapies, which cause patients and families discomfort and distress. Since PID has an unremitting course, early recognition is imperative, as it allows for prompt and efficacious antibiotic therapy. However, PID represents a stubborn condition and, even if properly treated, its recurrence rate remains high. Further well-designed prospective randomized controlled trials, with adequate follow-up, are required in order to formulate the optimum personalized antibiotic therapy (oral alone or in association with topical medication), able to prevent recurrences. Awareness of this condition by healthcare professionals should improve patient outcomes.