Leukemia Cutis in Relapsed Acute Myeloid Leukemia: A Call for Distinct Classification.

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

Eosinophil-rich linear IgA bullous dermatosis induced by mRNA COVID-19 booster vaccine.

We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.

Self-supervised artificial intelligence predicts recurrence, metastasis and disease specific death from primary cutaneous squamous cell carcinoma at diagnosis.

Primary cutaneous squamous cell carcinoma (cSCC) is responsible for ~10,000 deaths annually in the United States. Stratification of risk of poor outcome (PO) including recurrence, metastasis and disease specific death (DSD) at initial biopsy would significantly impact clinical decision-making during the initial post operative period where intervention has been shown to be most effective. In this multi-institutional study, we developed a state-of-the-art self-supervised deep-learning approach with interpretability power and demonstrated its ability to predict poor outcomes of cSCCs at the time of initial biopsy. By highlighting histomorphological phenotypes, our approach demonstrates that poor differentiation and deep invasion correlate with poor prognosis. Our approach is particularly efficient at defining poor outcome risk in Brigham and Women's Hospital (BWH) T2a and American Joint Committee on Cancer (AJCC) T2 cSCCs. This bridges a significant gap in our ability to assess risk among T2a/T2 cSCCs and may be useful in defining patients at highest risk of poor outcome at the time of diagnosis. Early identification of highest-risk patients could signal implementation of more stringent surveillance, rigorous diagnostic work up and identify patients who might best respond to early postoperative adjunctive treatment.

Acute exposure of Nicotine during Drosophila puncture injury activates an epidermal wound response reaction.

Epidermal wound reaction after injury can be visualized in Drosophila melanogaster embryos by transgenic fluorescent wound reporters. A "local" reaction is limited to the epidermal cells surrounding a wound site occurs in wildtype embryos. A "global" reaction extends beyond the wound site to all epidermal cells occurs in immune response mutants (e.g. Flotillin-2 and Toll). The aim of this investigation is to explore the effect of nicotine on the localization of Drosophila wound reaction. Nicotine may have the potential to negatively affect wound repair by inhibiting a local reaction, and ultimately impeding epidermal wound recovery in Drosophila. We find nicotine exposure activates a global reaction after puncture injury of Drosophila embryos. Determining the effect of nicotine exposure on wound reaction in Drosophila may lead to improved understanding of how nicotine use in humans may influence wound healing after tissue damage.

A systematic review of evidence based treatments for lichen simplex chronicus.

Lichen simplex chronicus (LSC) is a disorder characterized by thickened areas of skin from repeated rubbing or scratching. The multifactorial nature of LSC makes management difficult and there are currently no evidence-based guidelines for treatment. We conducted a systematic review of the literature to evaluate treatments for LSC and provide an evidence-based summary of the current treatments as well as highlight novel therapies. A total of 21 studies were included which comprised 682 patients with LSC involving various areas. The most robust evidence was seen with the use of topical corticosteroids (n = 7 RCTs) and limited data suggest benefit with other treatments such as topical immunomodulators, topical antipruritic agents, oral antihistamines, antiepileptics and antidepressants. We also discuss novel treatment approaches using transcutaneous electrical nerve stimulation, focused ultrasound, and phototherapy. Despite emerging evidence there remains a paucity of high-quality studies supporting treatments for LSC and larger controlled trials are needed.

Normal Gaze Patterns of the Face in Lateral View.

Importance: Current efforts to quantify the attentional distraction of facial deformities have been limited to deformities that are best perceived when the face is in frontal view, and there remains a paucity of knowledge of societal perception of the face in lateral view. To date, no attempts have been made to characterize the fixation patterns of the face in lateral view. Objective: To characterize the fixation patterns and gaze patterns of the face in lateral view. Design, Setting, and Participants: This was a prospective randomized controlled trial at an academic tertiary medical center. Eighty participants (mean age 23.6 ± 1.7 years, 52.5% female) gazed freely at 11 images of faces in lateral view for 10 s each as an infrared eye-tracker recorded eye movements in real time. Main Outcomes and Measures: Recorded eye movements are superimposed on the images to visualize areas of interest (AOIs) that attract the most attention. Fixation duration targeted at each AOI is transformed into relative fixation of the entire face and neck. Hotelling's test of variance followed by post hoc t-testing assessed for the significance of fixation differences between the mouth and cheeks. Results: Participants spent an average of 6.0 (95% CI 5.8-6.2) s gazing at the face and neck areas of each image. Of this attention, 2.8 s or 49.8% (45.4-54.2%) was directed toward the eye, followed distantly by the nose (mean, 95% CI) (16.4%, 14.5-18.3%), cheek (12.0%, 11.4-14.5%), neck (4.6%, 3.8-5.4%), and mouth (4.0%, 3.4-4.6%). These differences were found to be significant by Hotelling's analysis and post hoc testing. A student's t-test also indicated observers directed significantly more attention within the eye-nose-cheek triangle [4.6 s or 79.5% (75.6-83.5)] compared with the eye-nose-mouth triangle [4.1 s or 71.2% (66.9-75.5)] (p < 0.001). Conclusions and Relevance: When perceiving novel faces in lateral view, casual observers preferentially directed attention toward the eye, nose, and cheek. These findings suggest that we draw from a slightly different collection of features to build a schema of the sagittal face, which may serve to complement the central triangle and build upon a three-dimensional model of the "normal" human face. Level of Evidence: NA.

Transoral neck surgery prevents attentional bias towards the neck compared to open neck surgery.

OBJECTIVE: Measure attentional distraction of neck scars after open neck surgery compared to transoral endoscopic thyroidectomy via a vestibular approach (TOETVA) or transoral endoscopic parathyroidectomy via a vestibular approach (TOEPVA) using eye-tracking technology. METHODS: Casual observers viewed facial images of patients who underwent open neck surgery, TOETVA/TOEPVA, or no surgery (controls). An eye-tracking monitor recorded eye fixations in real time. Multivariate Hotelling's analysis followed by post-hypothesis testing compared fixation durations for predefined regions of interest, including the eyes, nose, mouth, neck, and remaining face between open neck surgery patients, transoral neck surgery patients, and controls. RESULTS: One hundred forty observers completed the experiment. The majority of their attention was directed towards the central triangle (eyes, nose, mouth). On multivariate analysis, distribution of attention was significantly different on the faces of those who underwent open neck surgery versus TOETVA/TOEPVA (T2 = 43.66; F[32,131] = 14.5389, P < .0001). Observers attended significantly more to the neck (0.20 seconds, P < .0001; 95% CI, 0.13, 0.26 s) and less to the peripheral face (-0.24 seconds, P = .0031; 95% CI, -0.39, -0.08 s) of open neck surgery patients. In patients who followed up months after surgery, significant differences persisted (T2 = 13.97; F[3451] = 4.6377, P = .0033). By contrast, fixation patterns for TOETVA/TOEPVA patients were not significantly different from controls (T2 = 5.59, F[31,186] = 1.8602, P = .1345). Observer race and gender did not significantly affect attention to neck scars. CONCLUSION: Scars following open neck surgery draw attention in casual observers. This attentional distraction is prevented in TOETVA/TOEPVA patients due to the absence of a scar, even months after surgery. Moreover, visual processing of TOETVA/TOEPVA patients' faces is similar to that of controls. These data support the effectiveness of transoral neck surgery in giving patients a cosmetic result that does not distract the attention of observers. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1603-1608, 2020.

Exploring Patient Motivations and Impact of Asian Blepharoplasty.

To date, patient motivations for Asian blepharoplasty and the surgery's impact on quality of life have not been quantified. Here, we employed structured interviews and a web-based survey to better characterize patient motivations for Asian blepharoplasty and the impact of Asian blepharoplasty on self-reported domains of happiness, self-esteem, attractiveness, social life, and professional life. Structured interviews were conducted to inform a web-based survey regarding Asian blepharoplasty. Survey respondents used visual analog scales to rate their satisfaction with their eye shape, motivations for undergoing Asian blepharoplasty, and perceived outcomes after surgery. A total of 315 participants (mean 25.7 [18-58] years) of East or Southeast Asian descent were included. 185 participants expressed no desire for Asian blepharoplasty, 76 expressed some desire, and 54 had already undergone surgery. There were statistically significant differences regarding baseline satisfaction, perceived social limitation, and perceived professional limitations regarding eye shape (p < 0.0001). The Looking Glass Self index (comprised of media exposure, low self-esteem, and negative stereotypes related to eye shape) is negatively associated with preoperative satisfaction with eye shape (rho = -0.29, p < 0.01). The desire for social-professional advancement and the Looking Glass Self index significantly predict self-reported improvements in professional and social life, respectively (both p < 0.01). Asian blepharoplasty may be driven by functional, social, or economic patient motivations. Some patients may see Asian blepharoplasty as a potential solution for sociological concerns. These expectations should be further explored in physician-patient discussions regarding candidacy for surgery and establishing expectations for postoperative outcomes.

Phototherapy in the Pediatric Population.

Phototherapy has been used successfully to treat a wide range of pediatric skin conditions. It is a viable option in children with severe dermatologic disease or who have failed first-line treatments, and several studies have demonstrated its efficacy and safety in the pediatric population. Despite the growing body of evidence on the use of phototherapy in children, large controlled trials and long-term studies are lacking. Moreover, special considerations must be taken when using phototherapy in children. This review highlights the recent evidence supporting the efficacy and safety of phototherapy in children, with focus on the common light-sensitive pediatric skin conditions.

Stretched Earlobe Piercings Negatively Impact Casual Observer Perceptions.

Patients with stretched earlobes seek reconstruction to mitigate social stigma. To date, there have been no studies measuring the impact of stretched earlobe piercings on casual observer perceptions. One-hundred seventy-three casual observers were enrolled via public-access web sites. Participants were randomly shown frontal and profile views of six subjects with stretched earlobe piercings and four controls. Participants evaluated photos for first impressions using a survey containing choices regarding personal attributes. Latent class analysis was performed to categorize observer ratings. Analysis of variance (ANOVA), bootstrap analysis, and permutations testing were used to evaluate the relationship between perceived attractiveness, success, and approachability scoring and stretched earlobe status. Latent class analysis categorized responses into three classes: positive, negative, and neutral. Patients with stretched earlobe piercings were significantly less likely to be classified as positive by observers without body modifications (i.e., tattoos and piercings) in comparison to control photos (30.9 and 40.1%, p = 0.007) and more likely to be classified as negative (38.5 and 28.1%, p = 0.002). These changes were abolished when photos were evaluated by observers with body modifications (p > 0.05). ANOVA revealed that stretched earlobe piercings and observer body modification status have a significant effect on rated approachability (F [1,1726] = 4.08, p = 0.04) and successfulness (F[1,1726] = 9.67, p = 0.002; F [1,1726] = 70.33, p < 0.0005). No significance was found for rated attractiveness (p > 0.05). Patients with stretched earlobe piercings were more likely to be classified as having negative affect display and being less approachable and successful compared with controls when evaluated by observers without body modifications. This effect was abolished when photos were evaluated by observers with body modifications. These findings validate patient motivations for seeking stretched earlobe repair.

Objectively measuring social attention of thyroid neck scars and transoral surgery using eye tracking.

OBJECTIVE: Measure the social attention of thyroid neck scars and transoral surgery using eye tracking. METHODS: Observers viewed images of patients with thyroid neck scars, control patients with no scars, and patients who underwent transoral thyroidectomy as an eye-tracking monitor recorded their eye movements. Hotelling's multivariate analysis, followed by planned posthypothesis testing, were used to compare fixation times for the central triangle (CT), peripheral face, and neck between the three groups. To assess if these gaze patterns would normalize with transoral surgery, a two-sample t test was done to assess for differences in neck fixations between control and transoral patients and between transoral and traditional thyroidectomy. RESULTS: One hundred and thirty participants completed the eye-tracking experiment (mean age 24.3 years, 65 females). Observers directed the majority of their attention to the CT in both control and scar patients. Observers paid more attention to the neck (103.72 ms, P < .0001, 95% confidence interval [CI] [55, 152] ms) and less to the peripheral face (115.50 ms, P = .01, 95% CI [19, 211] ms) in patients with neck scars than in control patients. Furthermore, transoral surgery eliminated this attentional distraction wherein there was no difference in the fixation time to the neck (-39.198 ms P = .16, 95% CI [-93.978, 15.5816] ms) between controls and those who underwent transoral surgery. CONCLUSION: Observers directed their gaze away from the face and toward the neck in patients with thyroid neck scars. Furthermore, this distraction was eliminated with tranoral surgery. These findings shed light onto the altered observer perceptions of patients with thyroid neck scars. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2789-2794, 2019.

Translating Research as an Approach to Enhance Science Engagement.

The impact of research depends on the effective communication of discoveries. Scientific writing is the primary tool for the dissemination of research, and is an important skill that biomedical trainees have to develop. Despite its importance, scientific writing is not part of the mainstream curriculum. One strategy used to teach scientific writing is holding a journal club style discussion of primary research literature that the students are asked to read. However, this activity can result in a passive learning experience and limit the development of trainees' scientific writing skills. In order to improve trainees' written communication skills, we tested an exercise that involved generating a revised article describing prior research, in essence "translating" the science into basic language. Following the guidelines set out by "Frontiers for Young Minds" and feedback received from "Young Reviewers", we wrote a revised article with a simpler description of the research. In this article, we describe this scientific writing exercise, which may ultimately serve as a model for scientists to share their research more efficiently in order to promote better public health outcomes.

Caracterización de niños menores de cinco años participantes en el programa médico nutricional de ORPHANetwork, Nicaragua en el período Primer Semestre 2015 y Segundo Semestre 2016 / Characterization of children under five years of age participating in the ORPHANetwork, Nicaragua nutritional medical program during the First Half 2015 and Second Half 2016

OBJETIVO: Caracterizar a los niños menores de cinco años participantes en el programa médico nutricional de ORPHANetwork, Nicaragua en el período primer semestre 2015 y segundo semestre 2016. DISEÑO: Descriptivo de corte transversal, se tomó una muestra de 340 niños menores de 5 años beneficiarios de la organización ORPHANetwork, en Nicaragua; a los cuales se les tomó talla y peso durante la visita de seguimiento del primer semestre 2015 y segundo semestre 2016, para realizar la valoración de desnutrición aguda, crónica y global toda la información se procesó en una base de datos; la cual se analizó por el programa de SPSS. RESULTADOS: Las principales características socio-demográficas de la población en estudio fueron 52.6% población femenina, en base a la edad 33.2% predominó de 36 a 47 meses, siendo la mayoría procedentes de la zona pacifico central. Al comparar los promedios con la prueba T de student se corrobora que existen diferencias estadísticamente significativas entre los promedios de talla del primer semestre 2015 y segundo semestre 2016, como en los promedios de peso en el primer semestre 2015 y segundo semestre 2016. El comportamiento de desnutrición crónica durante un año de seguimiento redujo 13% mejorando la calidad de vida de los niños en estudio, por otro lado la desnutrición aguda no presentó cambios significativos. CONCLUSIÓN: Las principales características socio-demográficas de la población en estudio fueron; población femenina, en base a la edad de 36 a 47 meses, predominando los procedentes de la zona pacifico central. Al comparar los promedios con la prueba T de student se corrobora que existen diferencias estadísticamente significativas entre los promedios de talla del primer semestre 2015 y segundo semestre 2016, como en los promedios de peso en el primer semestre 2015 y segundo semestre 2016. El comportamiento de desnutrición crónica durante un año de seguimiento redujo significativamente mejorando la calidad de vida de los niños en estudio, por otro lado la desnutrición aguda no presento cambios significativos

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis.

The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal-ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci.

Drosophila Embryos as a Model for Wound-Induced Transcriptional Dynamics: Genetic Strategies to Achieve a Localized Wound Response.

While many studies have established a paradigm for tissue repair at the level of cellular remodeling, it is not clear how an organism restricts a response only to the injured region of a damaged tissue. Skin, the largest organ in the human body, is prone to injury, and repair of epidermal tissue represents a medically relevant system to investigate. Significance: Studies in Drosophila melanogaster provide a robust genetic system to identify molecular components that will positively impact repair and healing. The Drosophila skin consists of a single-cell epidermal layer and relies on well-conserved cellular mechanisms to coordinate gene expression during development. Many studies have established that key developmental genes promote a response to epidermal injury, but the balance between activator and inhibitor signals to coordinate a localized response remains unknown. Recent Advances: Discovery of a genetic pathway that promotes the restriction of transcriptional response to damage only in effected regions. Interestingly, genome-wide microarray studies have identified an intersection between gene expression after aseptic injury and activation of the innate immune response. Critical Issues: The use of a transcriptional activation reporter provides an innovative approach to uncover well-conserved components that promote the localization of a response during epidermal injury and may influence other pathological conditions of tissue damage. Future Directions: The work reviewed in this critical review may lead to development of molecular strategies of repair and improved healing after injury or infection. The outcomes on the fundamental contribution of a transcriptional response to injury will be translatable to mammalian systems.