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Παρασκευή 28 Σεπτεμβρίου 2018

Current Therapeutic Approaches to DCIS

Abstract

Treatment for ductal carcinoma in-situ (DCIS) has historically been extrapolated from studies of invasive breast cancer. Accepted local therapy approaches range from small local excisions, with or without radiation, to bilateral mastectomies. Systemic treatment with endocrine therapy is often recommended for hormone positive patients. With improvements in imaging, pathologic review, and treatment techniques in the modern era, combined with new information regarding tumor biology, the management of DCIS is rapidly evolving. A multidisciplinary approach to treatment is now more important than ever, with a shift towards de-escalating therapy to reduce treatment related toxicity. This review focuses on nuances of clinical management of DCIS in the modern era, highlighting key differences between DCIS as compared to invasive breast cancer. The American Cancer Society (ACS) currently recommends beginning screening with annual mammograms for women age 45, with the option to start at age 40. As treatment of DCIS has not been shown to impact survival, the USPSTF has more conservative screening recommendations of biennial mammograms from age 50–74. Unlike invasive breast cancer, DCIS is almost exclusively diagnosed by mammographic detection, and lymph node evaluation is not recommended. Pathologic review of biopsy specimens should follow the guidelines of the College of American Pathologists. Surgical management options include breast conservation, mastectomy, or possibly nipple sparing mastectomy, with upfront sentinel lymph node evaluation in the case of mastectomy. Radiation therapy is generally recommended as a component of breast conserving therapy for patients with DCIS, though in some low risk patients, there is trial data to suggest that adjuvant radiation may be omitted. Techniques for minimizing radiation toxicity should always be emphasized. Endocrine therapy is offered to women with hormone positive DCIS who have undergone lumpectomy for risk reduction, and has the benefit of decreasing incidence of events in both the ipsilateral and contralateral breast. More recent studies have explored use of targeted treatments such as trastuzumab in DCIS for HER2 overexpression. Future directions include tailoring therapy based on patient characteristics and tumor biology. With so many different options for treatment, it is also critical to engage in a discussion with the patient to arrive at a treatment decision that balances patient preferences for disease control versus treatment toxicity, financial toxicity, cosmesis, and quality of life.



Current Therapeutic Approaches to DCIS

Abstract

Treatment for ductal carcinoma in-situ (DCIS) has historically been extrapolated from studies of invasive breast cancer. Accepted local therapy approaches range from small local excisions, with or without radiation, to bilateral mastectomies. Systemic treatment with endocrine therapy is often recommended for hormone positive patients. With improvements in imaging, pathologic review, and treatment techniques in the modern era, combined with new information regarding tumor biology, the management of DCIS is rapidly evolving. A multidisciplinary approach to treatment is now more important than ever, with a shift towards de-escalating therapy to reduce treatment related toxicity. This review focuses on nuances of clinical management of DCIS in the modern era, highlighting key differences between DCIS as compared to invasive breast cancer. The American Cancer Society (ACS) currently recommends beginning screening with annual mammograms for women age 45, with the option to start at age 40. As treatment of DCIS has not been shown to impact survival, the USPSTF has more conservative screening recommendations of biennial mammograms from age 50–74. Unlike invasive breast cancer, DCIS is almost exclusively diagnosed by mammographic detection, and lymph node evaluation is not recommended. Pathologic review of biopsy specimens should follow the guidelines of the College of American Pathologists. Surgical management options include breast conservation, mastectomy, or possibly nipple sparing mastectomy, with upfront sentinel lymph node evaluation in the case of mastectomy. Radiation therapy is generally recommended as a component of breast conserving therapy for patients with DCIS, though in some low risk patients, there is trial data to suggest that adjuvant radiation may be omitted. Techniques for minimizing radiation toxicity should always be emphasized. Endocrine therapy is offered to women with hormone positive DCIS who have undergone lumpectomy for risk reduction, and has the benefit of decreasing incidence of events in both the ipsilateral and contralateral breast. More recent studies have explored use of targeted treatments such as trastuzumab in DCIS for HER2 overexpression. Future directions include tailoring therapy based on patient characteristics and tumor biology. With so many different options for treatment, it is also critical to engage in a discussion with the patient to arrive at a treatment decision that balances patient preferences for disease control versus treatment toxicity, financial toxicity, cosmesis, and quality of life.



FDA Approves Cemiplimab, First Drug for Advanced CSCC

The US Food and Drug Administration today approved cemiplimab for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced, unresectable CSCC.
FDA Approvals

Trichothiodystrophy: A rare association of brittle hair, ichthyosis, and epilepsy

GS Asha, Tapasya S Kini, KS Chandan, P Mahanthesh

Indian Journal of Paediatric Dermatology 2018 19(4):357-359

Trichothiodystrophy (TTD) is a rare autosomal recessive genetic disorder characterized by abnormal synthesis of sulfur-containing keratins and consequently hair dysplasia, associated with numerous symptoms affecting mainly organs derived from the neuroectoderm. The deficiency of cysteine and methionine explains the fragility and the regular undulation of the hair shaft of patients with TTD, appreciated as the characteristic tiger tail appearance on polarized microscopy. We report a case of TTD with a rare association of brittle hair, ichthyosis, and epilepsy, classified as Tay syndrome based on clinical features and complementary examinations.

Seeing beyond, mimicker of genital lesions and a personal view

Ebtisam Elghblawi

Indian Journal of Paediatric Dermatology 2018 19(4):382-383



Allergic contact dermatitis in atopic dermatitis

Sandipan Dhar, Sahana M Srinivas, Ashok K Bajaj

Indian Journal of Paediatric Dermatology 2018 19(4):304-307

Atopic dermatitis (AD) coexisting with allergic contact dermatitis (ACD) is not uncommon. There has been lot of controversies regarding this concept as the prevalence of ACD in AD is similar to that seen in nonatopics. There is increased susceptibility to ACD in AD as AD modulates the exposure to allergens. There is an impaired barrier function that predisposes to the development of ACD in AD. Patch testing is a standard test for detecting allergens in AD.

Eczema herpeticum in a patient with atopic dermatitis, coxsackie B virus, and staphylococcal infection: A double skin damage

Andrea D Pratico, Valentina Fatuzzo, Maria Elena Cucuzza, Flavia M C La Mendola

Indian Journal of Paediatric Dermatology 2018 19(4):369-370

Eczema herpeticum is a rare viral skin scattered infection whose main etiologic agents are HSV1–2 and coxsackievirus, but its association with atopic dermatitis suggests that different factors may play a role in this complex phenotype. When not promptly treated, it can spread to other organs, causing severe complications such as keratoconjunctivitis, encephalitis, and meningitis. We describe the case of a patient with atopic dermatitis who came to our observation presenting with diffuse purulent vesicular lesions, whose bacterial culture was positive for Staphylococcus aureus and whose serologic examinations showed IgM positivity for coxsackie B virus.

Childhood psoriasis: What is new and what is news

Sunil Dogra, Anuradha Bishnoi

Indian Journal of Paediatric Dermatology 2018 19(4):308-314

Psoriasis is a chronic inflammatory disorder that affects around 2%–4% of the general population, and the prevalence can be higher in selected populations. About one-third of the people affected with psoriasis have the onset of their disease in the first and second decades of life. Of the pediatric population, about 0.5%–2% is affected. Infants are affected rarely. The incidence increases with age and is reported to be ~0.55% in the age group of 0–9 years and 1.37% in the age group of 10–19 years. Flexures, face, periauricular area and medial aspect of the upper eyelid are commonly involved in children. In infants, there is predilection for diaper area. Overall, plaque psoriasis is the most common type, followed by guttate and pustular psoriasis. Lesions are more pruritic, but thinner, less erythematous, and less scaly. Follicular lesions are common. Treating psoriatic erythroderma can pose difficulties, especially in pediatric population. Some cases achieve rapid control of disease activity, while others develop chronic erythroderma with frequent disease flares. The impact of disease on psychosocial parameters is significant in this subgroup of psoriasis and affects patients and parents alike with significantly high rates of absenteeism from school. Pediatric psoriasis therefore needs to be managed effectively. However, effective treatment also poses the risk of producing adverse effects, more so in pediatric age group. A delicate balance therefore should be maintained and overzealous treatment should be avoided.

Infantile hemangiomas: An update on pathogenesis, associations, and management

Karina L Vivar, Anthony J Mancini

Indian Journal of Paediatric Dermatology 2018 19(4):293-303

Infantile hemangiomas (IH) are the most common vascular neoplasm in infants. The typical clinical course of IH follows a pattern of growth (proliferation) followed by spontaneous involution. The majority of IH are isolated to the skin; however, some cutaneous IH can be associated with internal organ involvement or anomalies. IH which are functionally impairing, ulcerated or potentially disfiguring require therapy. Treatment options include systemic or topical beta-blockers, systemic or intralesional corticosteroids, pulsed dye laser therapy, or surgical excision. In this article, we review the updated understanding of IH pathogenesis, clinical presentations and associations, and approaches to management.

Does color really matter? Reliability of transcutaneous bilirubinometry in different skin-colored babies

Pearl Mary Varughese, Lalitha Krishnan, Ravichandran

Indian Journal of Paediatric Dermatology 2018 19(4):315-320

Background: Transcutaneous bilirubinometry, in keeping with rapid technological advances, has come a long way as an effective tool for assessing bilirubin levels in newborns. Though the early devices showed changes due to melanin concentration, the new generation devices were based on micro-spectrometry. Color coded scales were rarely used for the comparison. Hence the primary outcome is that TcBI is more reliable in lighter skin color babies than darker skin color babies.Objective: To study the reliability of TcB in different skin color babies. Materials and Methods: The study was conducted in a tertiary newborn center from November 2014 to June 2016. The inclusion criteria included all babies above 34 weeks gestation and exclusion criteria included babies with established direct hyperbilirubinemia, neonatal septicemia, major congenital/ gastrointestinal malformations and those on phototherapy. 396 babies were recruited. At 24 hours, babies were categorized based on Fitzpatrick skin color chart. Statistical analysis was done using the ROC curves Bland Altman charts. Results: Mean TcB was found to be uniformly higher than TSB for all variables like sex, birth weight, gestational age and growth of the baby with an excellent correlation (r = 0.698-0.932). 335 babies (74.4%) were falling in the color code 3. 113 babies (25.1%) were in the color code 4 and 2 babies (0.4%) were in the color code 5. TcB correlates better in light skin tone babies (color code 3) than dark skin tone babies (color code 4) with r= 0.874 and r= 0.856 respectively. Conclusion: Though TcB overestimates; it correlates well with TSB in lighter skin tone babies than babies with darker skin tone.

Klippel–Trenaunay syndrome affecting an uncommon site

Ibrahim Aliyu, Godpower Chinedu Michael

Indian Journal of Paediatric Dermatology 2018 19(4):363-365

Klippel–Trenaunay syndrome (KTS) is characterized by the triad of varicosity of cutaneous veins, port wine stains, and soft tissue/bone overgrowth. It was first described by French physicians Klippel and Trenaunay in 1900. There is often overlap between KTS and Parkes Weber syndrome. The lower extremities are mostly affected and it is usually asymmetric; other sites involved are the upper limbs, trunk, and rarely, the head and face region. Therefore, the case of a 5-year-old girl who presented with KTS symmetrically involving the trunk and lower limbs is reported.

A hospital-based clinical study of childhood psoriasis in a tertiary care center of Northeast India

Seujee Das, Pankaj Adhicari

Indian Journal of Paediatric Dermatology 2018 19(4):321-325

Background: Childhood psoriasis has been reported to differ from that among adults. There are a limited number of studies on childhood psoriasis and none from the north-eastern part of India. A detailed clinical study will help to understand better the disease profile in children, thereby assisting in better diagnosis and treatment. Objective: The objective of this study was the clinical profile of childhood psoriasis. Materials and Methods: The present observational study was conducted in the Dermatology Outpatient Department of Assam Medical College and Hospital, Dibrugarh, during 12 months from June 2014 to May 2015. All children up to 13 years presenting with psoriasis during 1 year were taken as study participants after obtaining the written consent from the sole guardian. A detailed examination and relevant investigations were done, whenever necessary. The findings were recorded in a pro forma for the analysis and interpretation of data. Results: A total of 26 cases of childhood psoriasis were recorded during the study. The prevalence of childhood psoriasis in our outpatient pediatric population was 1.24%. Female cases (19; 73.08%) outnumbered male cases (7; 26.92%). A maximum number of cases were noted in 9–13 years of age group. The lower extremities (11; 42.31%) were the most common site of onset. Plaque type (14; 53.85%) was found to be the most common type. About 7.69% cases had a positive family history. Conclusion: Frequent involvement of soles was noted in childhood psoriasis similar to other parts of India but unlike other parts of the world. Pediatric patients had significantly more involvement of the trunk, face, and groin than did adult patients.

Hot topics in pediatric dermatology

Vishal Thakur, Dipankar De

Indian Journal of Paediatric Dermatology 2018 19(4):375-379



Clinicomycological study of dermatophytoses in children: Presenting at a tertiary care center

Nitin Mishra, Madhur Kant Rastogi, Pratik Gahalaut, Sandhya Yadav, Neeraj Srivastava, Anuj Aggarwal

Indian Journal of Paediatric Dermatology 2018 19(4):326-330

Background: Superficial tinea infections are some of the most common dermatological conditions in children. Recently, few studies done showed abrupt increase in dermatophytic infection in adults; however, similar recent studies describing clinicoepidemiological pattern in pediatric population are lacking. Aims and Objectives: The aims and objectives of this study are to identify the epidemiological profile of the dermatophytoses among pediatric population. Materials and Methods: Pediatric patients with suspected tinea infections presenting in the Department of Dermatology at a tertiary care medical college hospital in Northern India from April 2016 to 2017 were evaluated for inclusion in this study. Samples were collected in two parts; if first part was found to be potassium hydroxide (KOH) positive for septate hyphae, the second part was sent for fungal culture subsequently. Statistical Analysis Used: SPSS version 20 was used for statistical analysis. Results: Out of 235 patients, 152 were male and 83 were female. Only 200/235 (85.1%) KOH positive enrolled patients yielded positive fungal culture. Most common species identified on culture was Trichophyton mentagrophytes, followed by Trichophyton rubrum, and Trichophyton violaceum. Trunk was the most common site affected in 29.4% patients, palms and soles were least affected. Conclusion: More number of patients applied topical steroid for a longer period of time in patients with extensive disease as compared to limited disease. The present study provides evidence that dermatophytosis in pediatric patients is following the pattern of adult dermatophytosis clinically and microbiologically now.

An unusual presentation of congenital melanocytic nevus

Ibrahim Aliyu

Indian Journal of Paediatric Dermatology 2018 19(4):385-386



Epidemiology of pediculosis capitis among schoolchildren in Damascus, Syria

Mohammad Taher Ismail, Mohammad Maher Kabakibi, Abeer Al-Kafri

Indian Journal of Paediatric Dermatology 2018 19(4):331-334

Background: Pediculosis is a common ectoparasitic infection in schoolchildren, causing a public health problem, which is neglected in Syria. Objective: This study aimed to determine the prevalence of infestation with head lice among primary schoolchildren in Damascus, Syria, and explore the predisposing factors of head lice infestation in public schools. Materials and Methods: The present study was to determine the head lice infestation (pediculosis) levels in primary schoolchildren, from March to July 2017. A total of 8689 (females: 4392, males 4297) schoolchildren aged 6–12 years from 18 selected primary school of Damascus city and countryside were examined for head lice. Pediculosis was defined as the presence of at least on living adult, nymph, or viable egg. Results: The overall head lice infestation rate was 14. 3% (1243/8689) and infestation rate was higher in girls (23.72%, 1042/4392) than in boys (4.67%, 201/4297). The infestation rate among schoolchildren varied from 1.4% to 60.7% and depended on the age group is 18.10% (6–8 years), 12.22% (9–10 years), and 13.30% (11–12 years). The infestation rate among girls varied from 22.2% (10–12-year-old group) to 42.8% (6–8-year-old group). Conclusions: Pediculosis is a common public health problem affecting primary schoolchildren in Damascus area, and the levels of infestation are of an endemic significance.

Lymphoplasmacytic plaque in children: An emerging new clinical entity

Sadhika Ganni, Sasi Kiran Attili, Raghurama Rao Gandikota, Kollipara Haritha

Indian Journal of Paediatric Dermatology 2018 19(4):354-356

Pretibial lymphoplasmacytic plaque in children is a rare emerging clinicopathological entity characterized by asymptomatic benign solitary plaque. Most of the cases are reported in healthy females. The treatment of choice is topical steroids.

Reticulate dyschromia, congenital atrichia and speech delay in a child: A diagnostic dilemma

Tasleem Arif, Mohammad Adil, Syed Suhail Amin

Indian Journal of Paediatric Dermatology 2018 19(4):335-338

Disorders of reticulate dyschromia can be diagnosed on the basis of the distribution and type of pigmentation in association with coexisting abnormalities. We describe a 4-year-old male child with reticulate dyschromia of the dorsal aspects of hands and feet and over the axillae, buttocks, and groins. The child had near complete absence of hair over body since birth. Skin-colored firm papules were present over dorsal aspects of hands and feet, and milestones were delayed for speech. We discuss the probable differentials in this article and why it fits none of the existing differentials.

Restrictive dermopathy: Report of two cases

Anisha K Janardhanan, Sarita Sasidharanpillai, Aparna S Vidya, Babu Francis, Mohandas Nair Karippoth

Indian Journal of Paediatric Dermatology 2018 19(4):360-362

Restrictive dermopathy is a rare entity that is fatal in the neonatal period itself. The rigidity of the skin leads to erosions, contractures, and restriction of respiratory movements. Diagnosis is often made clinically with classical features such as low-set ears, micrognathia, small, and persistently open fixed "o"-shaped mouth, translucent, shiny, rigid skin with prominent superficial blood vessels, and pseudocontractures of limb joints. We report two cases of restrictive dermopathy observed in our center within 2 years period and suggest that this condition may not be as rare as believed.

Bleomycin-induced flagellate dermatosis in a 7-Year-Old child: A case report with review of literature

Preeti Sharma, Rajesh Sinha, Dhiraj Kumar, Amit Kumar

Indian Journal of Paediatric Dermatology 2018 19(4):339-341

A 7-year-old female known case of nonseminomatous germ cell tumor was on treatment with bleomycin, etoposide, and cisplatin (BEP) regimen. After completing two cycles of BEP regimen, she developed linear hyperpigmented lesions in flagellate-like pattern on the trunk, neck, arms, and legs. After cessation of bleomycin, the patient started to improve.

Idiopathic localized involutional lipoatrophy in a child with spontaneous resolution

Reena Kumari Sharma, Mudita Gupta, Anuj Sharma

Indian Journal of Paediatric Dermatology 2018 19(4):366-368

Idiopathic localized involutional lipoatrophy (ILIL) is focal loss of subcutaneous tissue without any clinical or histopathological inflammation. Histopathology of ILIL characteristically shows diminutive fat lobules composed of small adipocyte resembling embryonic fat tissue. Immunohistochemical examination reveals a number of CD-68 positive macrophages in the fat lobules. Most reported cases of ILIL were unilateral in young women; we are reporting a case of 4-year-old child with bilateral involvement showing quick spontaneous resolution.

Dermoscopy of branchial fistula

Subrata Malakar, Priya Diwaker, Pratibha Pradhan

Indian Journal of Paediatric Dermatology 2018 19(4):342-343

Branchial fistula is a congenital anomaly resulting from failure of closure of one of the four branchial clefts. It is usually a clinical diagnosis, but dermoscopy helps in highlighting its features, thereby avoiding the need of imaging studies and other invasive diagnostic procedures. Here, we report a case of 3-year-old female patient who presented with asymptomatic tiny papule on the neck since early childhood. Dermoscopy was done to describe the features of branchial fistula and cleft.

Hutchinson's signs in dermatology

Manjyot Gautam, Palak Sheth

Indian Journal of Paediatric Dermatology 2018 19(4):371-374



Japan Singapore Skin Conference 2019



The Editor's Choice



Editorial board



Confucius and Kierkegaard: A Compatibilist Account of Social Ontology, Acquired Selfhood, and the Sources of Normativity

Abstract

Nearly all of the scant comparative work on Søren Kierkegaard and Confucius places the two starkly at odds with each other. Kierkegaard is pictured as the paradigmatic exemplar of the Western self: a discrete rights-bearing and volitional atom who is quite alone in the world, while Confucius, by contrast, is the paradigmatic exemplar of the Eastern self: a complex and irreducibly embedded communitarian bundle of relations and rich social roles. In this article, I challenge this oppositional approach, since it is both erroneous and obscures fruitful dialogue between the two on conceptually commensurate problems. I argue (1) that Kierkegaard offers a relational ontology of the self which moves in a Confucian direction, (2) that subjectivity and relational reciprocity are not fundamentally at odds in the two thinkers, (3) that both thinkers value a life of harmonious integration that entails right relation to others, and finally (4) that Confucius' appeal to Heaven as a source of normativity allows for salutary social critique of prevailing ethical norms and practices, in a way that provides important comparative insights with Kierkegaardian theism.



Wang, Daiyu, The First Islamic Classic in Chinese: W ANG Daiyu’s Real Commentary on the True Teaching



Wittgenstein and the Xunzi on the Clarification of Language

Abstract

Broadly speaking, language is part of a social activity in both Wittgenstein and Xunzi 荀子, and for both clarification of language is central to their philosophical projects; the goal of this article is to explore the extent of resonance and discord that may be found when comparing these two philosophers. While for Xunzi, the rectification of names (zhengming 正名) is anchored in a regard for establishing, propagating, and/or restoring a harmonious social system, perspicuity is for Wittgenstein represented as a philosophical end in itself. The article ventures study in particular the themes of perspicuity and aspect-perception in Wittgenstein together with the topics of correcting names and the cultivation of the heart-mind (xin 心) in the Xunzi. The aspiration of this project is to gain an overview of the role(s) of clarification projects in different philosophical traditions, all while not overlooking the different historical contexts and philosophical ends of these two philosophers.



On the Interpreter’s Choices: Making Hermeneutic Relativity Explicit

Abstract

In this essay, we explore the various aspects of hermeneutic relativity that have rarely been explicitly discussed. Our notion of "hermeneutic relativity" can be seen as an extension, with significant revisions, of Gadamer's notion of Vorurteil. It refers to various choices and constraints of the interpreter, including beliefs concerning the best way of doing philosophy, what criteria are to be used to evaluate competing interpretations, and so on. The interpreter cannot completely eliminate the guidance and constraint originating from his/her "background." However, in principle the interpreter can "choose" to be guided by other constraints. Hence, we speak of "choices" or "commitments." Hermeneutic relativity is the major cause for the variation of competing interpretations.



Is the Question “Who Does the Sounding?” Meaningful?



Anscombe’s “I,” Zhuangzi’s Pipings of Heaven, and The Self That Plays the Ten Thousand Things: Remarks on Thomas Ming’s “Who Does the Sounding?”



Antiviral potentials of Lactobacillus plantarum , Lactobacillus amylovorus , and Enterococcus hirae against selected Enterovirus

Abstract

Enteroviruses have been associated with a host of clinical presentations including acute flaccid paralysis (AFP). The site of primary replication for most enteroviruses is the gastrointestinal tract (GIT) and lactic acid bacteria (LAB) may confer protection in the GIT against them. This study therefore investigates the antiviral potential of some selected lactic acid bacteria against enterovirus isolates recovered from AFP cases. The antiviral activities of Lactobacillus plantarum, Lactobacillus amylovorus, and Enterococcus hirae in broth culture, their cell-free supernatant (CFS), and bacterial cell pellets were assayed against Echovirus 7 (E7), E13, and E19 in a pre- and post-treatment approach using cytopathic effect (CPE) and cell viability (MTT) assay. The tested Lactobacillus plantarum, Lactobacillus amylovorus, and Enterococcus hirae strains have good antiviral properties against E7 and E19 but not against E13. Lactobacillus amylovorus AA099 shows the highest activity against E19. The pre-treatment approach displays better antiviral activities compared to post-treatment approach. The LAB in broth suspension have better antiviral activities than their corresponding CFS and bacterial pellet. Lactic acid bacteria used in this study have the potential as antiviral agents.



NEDD4 is involved in inflammation development during keloid formation

Keloids mark a chronic inflammatory disease characterized by a fibroproliferative disorder of the skin. A genome-wide association study (GWAS) has revealed that single nucleotide polymorphism (SNP) rs8032158 in the neural precursor cell expressed, developmentally down-regulated 4 (NEDD4) gene, which has six protein-coding transcript variants (TV), is genetically linked with keloid. Here we show a high frequency of the risk allele C in rs8032158 in keloid patients is associated with a selectively higher expression of TV3 of NEDD4 to activate the NFκB pathway.

Notch-signaling activity determines uptake and biological effect of imatinib in systemic sclerosis dermal fibroblasts.

Tyrosine kinase inhibitors (TKI) have emerged as therapeutic option for rheumatic diseases such as systemic sclerosis (SSc). Since TKs like c-Abl kinase are important for fibroblast activation and fibrosis development in SSc, the c-Abl inhibitor imatinib was proposed for SSc treatment. Transporters for organic cations have become increasingly recognized as an important determinant for uptake and efficacy of TKI. Therefore, we investigated the role of organic cation transporters in the uptake of imatinib.

Imaging of salivary gland pathology

The major salivary glands can be affected by a variety of acute or chronic, systemic, and neoplastic conditions. Several modalities can be used for salivary gland imaging, each with its own advantages and limitations. The article reviews the optimal imaging modality for different clinical scenarios, the typical imaging appearance of commonly encountered pathologies, and seeks to provide a framework for generating an appropriate differential diagnosis. Additionally, with regard to neoplastic conditions, the goals of the review are to highlight features suggestive of benign or low-grade lesions verses high grade malignancy, while recognizing the limitations of imaging in making specific histologic diagnoses.

CDKN2A germline mutations are not associated with poor survival in an Italian cohort of melanoma patients

Cyclin dependent kinase inhibitor 2A gene (CDKN2A) germline mutations have recently been associated with poor survival in patients with melanoma. Despite the high mutation rate in our cohort (up to 10% in patients with apparently sporadic melanoma), information on the impact of CDKN2A on survival in this cohort is lacking.

Exchanging for Reasons, Right and Wrong



Constructivism and the Problem of Normative Indeterminacy



Mechanisms, resources, and background conditions

Abstract

Distinguishing mechanistic components from mere causally relevant background conditions remains a difficulty for mechanistic accounts of explanation. By distinguishing resources from mechanical parts, I argue that we can more effectively draw this boundary. Further, the distinction makes obvious that there are distinctive resource explanations which are not captured by a traditional part-based mechanistic account. While this suggests a straightforward extension of the mechanistic model, I argue that incorporating resources and resource explanations requires moving beyond the purely local account of levels that some mechanists advocate.



Histiocitosis de células de Langerhans cutánea de presentación en el adulto

Publication date: Available online 27 September 2018

Source: Actas Dermo-Sifiliográficas

Author(s): M.A. Flores-Terry, J.L. Sanz-Trenado, M. García-Arpa, M.P. Cortina-de la Calle



Placa hiperqueratósica asintomática en glande en un varón de mediana edad

Publication date: Available online 27 September 2018

Source: Actas Dermo-Sifiliográficas

Author(s): P. Aguayo-Carreras, F.J. Navarro-Triviño, R. Ruiz-Villaverde, S. Saenz-Guirado



The anatomy of the superficial temporal artery in patients with unilateral microtia.

Publication date: Available online 28 September 2018

Source: Journal of Plastic, Reconstructive & Aesthetic Surgery

Author(s): Clara M. Olcott, Patrick E. Simon, Thomas Romo, William Louie

Summary
Background

This is a retrospective study that evaluated the anatomical distribution of the superficial temporal artery (STA) in supply of the temporoparietal fascial (TPF) flap for use in unilateral microtia patients undergoing reconstruction. We aimed to determine if embryologic arrest of pharyngeal arch development would lead to aberrant STA which impedes reliable harvest of the TPF flap in patients requiring microtia repair.

Methods

CT angiograms (CTA) and 3-D reconstruction of the face and neck of 41 microtia patients, aged 6 to 21 years, were examined. The number of STA branches, branching pattern, vessel diameter, and the presence or absence of the external auditory canal atresia were documented.

Results

The superficial temporal artery crosses the zygoma on average 4mm more anterior to the porion (anterior-inferior lip of the tympanic part of temporal bone) on the side with microtia compared to the non-microtia side. There were no statistically significant differences between vessel caliber or STA branches between the two sides.

Conclusion

The STA is anatomically reliable for inclusion in TPF flaps being used in auricular reconstruction for microtia patients. A TPF flap can be safely harvested with routine technique, though surgeons should be cognizant of the STA coursing more anteriorly on the microtia ear.



Lipoidoproteinosis o enfermedad de Urbach-Wiethe: presentación de un caso y revisión de la literatura

Publication date: Available online 27 September 2018

Source: Piel

Author(s): Raquel Ávila, Valmore Bermúdez, Maricarmen Chacín González, Eylineth Vílchez, Ismael Contreras



Histiocitoma fibroso maligno y sarcoma pleomórfico indiferenciado, ¿son la misma entidad?

Publication date: Available online 27 September 2018

Source: Piel

Author(s): Camilo E. Alarcón Pérez, Ana M. Álvarez Mantilla, Óscar Mora Hernández, Juan Carlos Hiromi López Takegami, Fernando Palma Escobar, Patricia de Castro Lotero



Postoperative complications of male to female sex reassignment surgery: A 10-year French retrospective study

Publication date: Available online 27 September 2018

Source: Annales de Chirurgie Plastique Esthétique

Author(s): S. Cristofari, B. Bertrand, S. Leuzzi, K. Rem, J. Rausky, M. Revol, M. Atlan, A. Stivala

Summary

In primary male to female (MTF) sex reassignment surgery (SRS), the most frequent postoperative functional complications using the penoscrotal skin technique remain neovaginal stenosis, urinary meatal stenosis and secondary revision surgery. We aimed to retrospectively analyze postoperative functional and anatomical complications, as well as secondary procedures required after MTF SRS by penile skin inversion. All patients operated on for MTF SRS, using the inverted technique, from June 2006 to July 2016, were retrospectively reviewed. The minimum follow-up was one year (five-years maximum follow-up). Soft postoperative dilationprotocol was prescribed until complete healing of the vagina. We did not prescribe long-term hard dilation systematically. Possible short-depth neovaginas were primarily treated with further temporary dilation using a hard bougie. Among the 189 included patients, we reported a 2.6% of rectovaginal wall perforations. In 37% of patients we had repeated compressive dressings and 15% of them required blood transfusions. Eighteen percent of patients presented with hematoma and 27% with early infectious complications. Delayed short-depth neovagina occurred in 21% of patients, requiring additional hard dilatation, with a 95.5% success rate. Total secondary vaginoplasty rate was 6.3% (4.7% skin graft and 3.7% bowel plasty). Secondary functional meatoplasty occurred in 1% of cases. Other secondary cosmetic surgery rates ranged between 3 to 20%. A low rate of secondary functional meatoplasty was showed after MTF SRS by penile skin inversion. Hard dilation was prescribed in case of healed short-depth vagina, with good efficiency in most of cases. Secondary vaginoplasty was required in cases of neovagina stenosis or persisting short-depth neovagina after failure of hard dilation protocol.

Résumé

Dans la chirurgie de réattribution sexuelle (SRS) primaire masculine à féminine, les complications fonctionnelles postopératoires les plus fréquentes utilisant la technique de la peau pénoscrotale restent la sténose néovaginale, la sténose urinaire et la reprise secondaire. Nous avons cherché à analyser rétrospectivement les complications fonctionnelles et anatomiques postopératoires, ainsi que les procédures secondaires requises après un SRS MTF par inversion de la peau du pénis. Tous les patients opérés pour le SRS MTF, en utilisant la technique inversée, de juin 2006 à juillet 2016, ont été revus rétrospectivement. Le suivi minimum était d'un an et le maximum était de cinq ans. Un protocole de dilatation postopératoire souple a été prescrit jusqu'à guérison complète du vagin. Nous n'avons pas prescrit une dilatation dure à long terme systématiquement. Les néovagins de faible profondeur possible ont été traités principalement avec une dilatation temporaire supplémentaire en utilisant une bougie dure. Parmi les 189 patients inclus, nous avons rapporté 2,6 % des perforations de la paroi rectovaginale. Chez 37 % des patients, nous avions des pansements compressifs répétés et 15 % d'entre eux nécessitaient des transfusions sanguines. Dix-huit pour cent des patients présentaient un hématome et 27 % présentaient des complications infectieuses précoces. Vingt et un pour cent des patients ont présenté un court néovagin en différée, nécessitant une dilatation dure supplémentaire, avec un taux de réussite de 95,5 %. Le taux de vaginoplastie secondaire totale était de 6,3 % (4,7 % de greffe de peau et 3,7 % de plastie intestinale). Une veinoplastie fonctionnelle secondaire est survenue dans 1 % des cas. Les autres taux de chirurgie esthétique secondaire se situaient entre 3 et 20 %. Un faible taux de meatoplastie fonctionnelle secondaire a été montré après MTF SRS par inversion de la peau du pénis. Une dilatation dure a été prescrite en cas de vagin guéri à faible profondeur, avec une bonne efficacité dans la plupart des cas. Une vaginoplastie secondaire a été nécessaire en cas de sténose à néovagin ou de néovagin à faible profondeur persistante après l'échec du protocole de dilatation dure.



Prélever un SIEP à la place d’un DIEP en reconstruction mammaire : note technique

Publication date: Available online 27 September 2018

Source: Annales de Chirurgie Plastique Esthétique

Author(s): Q. Bettex, C. Jaloux, M. Abellan Lopez, D. Casanova, B. Bertrand, C. Philandrianos

Résumé

La reconstruction mammaire par lambeau abdominal a évolué vers une diminution des séquelles du site donneur depuis la description du lambeau perforant de DIEP (pour Deep Inferior Epigastrique Perforator). De même épaisseur et de même surface, le lambeau de SIEA (pour Superficial Inferior Epigstrique Artery) ne nécessite pas, pour son prélèvement, d'ouverture de la gaine abdominale ni de dissection au travers des muscles grands droits, minimisant encore les séquelles. Cependant, il est peu utilisé en raison de la variabilité de sa vascularisation et d'un taux d'échec plus élevé que le DIEP dans la littérature. Nous pensons qu'il est tout de même raisonnable, dans certains cas, de prélever un SIEA à la place d'un DIEP. Nous présentons une note technique expliquant notre stratégie opératoire permettant de prélever un SIEA de façon fiable lorsque le calibre des vaisseaux le permet.

Summary

Breast reconstruction by abdominal flap has evolved to ensure minimal donor-site morbidity with the description of Deep Inferior Epigastric artery Perforator flap (DIEP flap). Being of the same thickness and the same surface, the Superficial Inferior Epigastric Artery flap (SIEA flap) does not require, for it harvesting, to open the abdominal fascia or to dissect through the muscles minimizing again donor-site sequelae. However, it is little used because of the variability of its vascularization and a higher failure rate than the DIEP in the literature. We believe that it is reasonable, in some cases, to harvest a SIEA flap instead of DIEP flap in mammary reconstruction. We present a technical note explaining our operative strategy for reliably taking a SIEA when the caliber of the vessels allows.



Psychiatric Dermatology: Management

Publication date: Available online 27 September 2018

Source: Clinics in Dermatology

Author(s): Madhulika A. Gupta



Case of bilateral elastofibroma on the tensor fasciae latae

The Journal of Dermatology, EarlyView.


Is Monogamy Morally Permissible?



More on the MORE Life Experience Model: What We Have Learned (So Far)



Breast Lipofilling Does Not Pose Evidence of Chronic Inflammation in Rats

Abstract
Background
Fat grafting to the breast has a questionable oncologic risk according to laboratory reports on adipose tissue. One possible reason for this is the theoretical chronic inflammation due to adipokynes released by the grafted white adipose tissue (WAT).
Objectives
Analyze inflammatory activity in lipofilled breast through proinflammatory markers.
Methods
Fifty-four paired-breasts of female rats were divided into four groups (control, sham, breasts grafted with autologous WAT of subcutaneous - SC, and of omentum - OM). The WAT was prepared through centrifugation and the grafting was performed via 0.9mm blunt tip cannula. The rats were euthanized at 8 weeks postoperatively, and their breasts were harvested for immunohistochemical staining for CD68-expressing macrophages, gene expression (real-time PCR) for Mcp-1, F4/80, Cox-2 and IL-6.
Results
The rats' weight differs between groups that underwent a procedure and the unmanipulated control (p<0.01). The macrophage counting of CD68 was different only between breasts lipofilled with OM and control (p<0.01). Mcp-1, F4/80 and Cox-2 were similarly expressed among the groups (respectively p=0.422, p=0.143 and p=0.209). The expression of IL-6 was different between samples of breast grafted with WAT of omentum and subcutaneous (p=0.015), but not between samples of control and omentum (p=0.752), and control and subcutaneous (p=0.056).
Conclusions
No inflammation activity was identified in the microenvironment of lipofilled breasts. This illustrates that chronic inflammation does not seem to be trigged by the breast lipofilling procedure.

Surgical Lip Remodeling After Injection of Permanent Filler

Abstract
Background
A major concern regarding permanent lip fillers is difficulty with revision, if warranted. Currently, the only way to treat lip sequelae is by surgical remodeling.
Objectives
Based on the senior author's 6-year experience, the authors collectively suggest a surgical method to correct lip deformity in such situations.
Methods
The records of 38 patients with lip deformity who underwent surgery between 2011 and 2017 after receiving permanent filler injections were analyzed retrospectively. A total of 38 consecutive patients, 69 lips, with an average age of 38.8 years (range, 28-52 years) were treated surgically.
Results
All patients experienced postoperative swelling (average duration, 15 days), and no infections were recorded. In 3 cases, a 1-cm dehiscence was documented, which healed by second intention. In 1 case, a hematoma noted several days after surgery resolved spontaneously within 3 weeks. In 2 upper lips, a minor touchup procedure (with the patient under local anesthesia) was performed 9 months after the initial surgery. Overall, patients noted that it took at least 6 to 9 months to achieve natural lip movement. The average time until softening of the lip tissue was 4 months.
Conclusions
This study emphasizes the importance of informing patients that complete removal of permanent filler is not always possible. However, most of the authors' patients were pleased with the results. This study also highlights the importance of paying strict attention when approaching the area adjacent to the oral commissures in order to avoid potential reductions in mouth opening that can occur from postoperative scarring.

Tofacitinib for the treatment of lichen planopilaris: A case series

Dermatologic Therapy, EarlyView.


Seltene Komplikation nach bilateralem MS2-TRAM-Flap

Zusammenfassung

Vorstellig wurde eine 49 Jahre alte Patientin mit Beschwerden, bei der 2 Jahre zuvor auswärts eine prophylaktische Mastektomie beidseits und ein Simultanaufbau beidseits durchgeführt worden waren. Als Grund für die geschilderten Beschwerden stellte sich ein in situ belassener Wundspreizer heraus. Dies macht deutlich, dass Beschwerden des Patienten ernst zu nehmen sind und bei Persistieren einer unklaren Problematik eine erweiterte Diagnostik erfolgen sollte.



Treatment of Vocal Cord Paralysis by Autologous Fat Injection: Our Experience with 41 Patients

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


A 20 year observational cohort of a 5 million patient population – tonsillectomy rates in the context of two national policy changes

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


Our Experience of Long Term Result of Tympanoplasty Using Areolar Tissue in 359 patients

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


Snoring sound energy as a potential biomarker for disease severity and surgical response in childhood obstructive sleep apnea: a pilot study

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


Histone modifications associated with biological drug response in moderate‐to‐severe psoriasis

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


Effects of extracorporeal photopheresis on serum levels of vitamin D: Preliminary Data from a Pilot Study

Photodermatology, Photoimmunology &Photomedicine, Volume 0, Issue ja, -Not available-.


Topical nicotinic receptor activation improves wound bacterial infection outcomes and TLR2‐mediated inflammation in diabetic mouse wounds

Wound Repair and Regeneration, Volume 0, Issue ja, -Not available-.


Use of cold atmospheric pressure plasma to treat warts: a potential therapeutic option

Clinical and Experimental Dermatology, EarlyView.


A painful vegetating finger

Clinical and Experimental Dermatology, EarlyView.


Loricrin palmoplantar keratoderma: full‐thickness skin grafting for pseudoainhum

Clinical and Experimental Dermatology, EarlyView.


Impact of a combined dermatology–rheumatology clinic on management of autoimmune connective tissue disorders

Clinical and Experimental Dermatology, EarlyView.


Melanocytic soluble adenylyl cyclase protein expression around lentigo maligna and in contralateral control skin

Clinical and Experimental Dermatology, EarlyView.


Erythematous lesion with peripheral purpura on the face

Clinical and Experimental Dermatology, EarlyView.


Grover disease and bullous pemphigoid: a clinicopathological study of six cases

Clinical and Experimental Dermatology, EarlyView.


Morse code‐like hairs in tinea capitis disappear after successful treatment

International Journal of Dermatology, EarlyView.


Fibroepithelioma of Pinkus in a 6‐year‐old boy: a case report

International Journal of Dermatology, EarlyView.


Pitfalls in diagnosing primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


Outcomes following SRS for small- to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose

Abstract
Background
At our institution, we have historically treated brain metastasis (BM) ≤2cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes.
Methods
We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariable analyses (MVA).
Results
1,533 BM ≤2cm were evaluated. Median radiographic follow-up post SRS was 12.7 months (1.4-100). Overall, the 2year incidence of LF was lower for BM treated with PD≥21Gy (9.3%) compared with PD≤15Gy (19.5%);(subHR 2.3; 95CI 1.4-3.7;p=0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21Gy (9.5%) compared to the PD ≤15Gy group (7.5%) (p=0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1cm) were significantly correlated (p<0.05) with higher rates of LF, and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15Gy to ≥21Gy, the risks of LF and RN are equivalent. However, for lesions >1cm, PD ≥21Gy is associated with a lower incidence of LF without significantly increasing the risk of RN.
Conclusion
Our results indicate that rates of LF or RN following SRS for BM are strongly correlated to size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brain stem.

Sex difference of mutation clonality in diffuse glioma evolution

Abstract
Background
x differences in glioma incidence and outcome have been previously reported but remain poorly understood. Many sex differencesthat affect the cancer risk were thought to be associated with cancer evolution.
Material/Methods
In this study, we used an integrated framework to infer the timing and clonal status of mutations in ~600 diffuse gliomas from The Cancer Genome Atlas including glioblastomas (GBM) and low grade gliomas (LGG), and investigated the sex difference of mutation clonality.
Results
We observed higher overall and subclonal mutation burden in female patients with different grades of gliomas, which could be largely explained by the mutations of X-chromosome. Some well-established drivers were identified showing sex-biased clonality, such as CDH18 and ATRX. Focusing on glioma subtypes, we further found a higher subclonal mutation burden in females than males in the majority of glioma subtypes, and observed opposite clonal tendency of several drivers between male and female patients in a specific subtype. Moreover, analysis of clinically actionable genes revealed that mutations in genes of mitogen-activated protein kinase (MAPK) signaling pathway were more likely to be clonal in female patients with GBM, whereas mutations in genes involved in receptor tyrosine kinase (RTK) signaling pathway were more likely to be clonal in male patients with LGG.
Conclusions
The patients with diffuse glioma showed sex-biased mutation clonality (e.g. different subclonal mutation number and different clonal tendency of cancer genes), highlighting the need to consider sex as an important variable for improving glioma therapy and clinical care.