Up-regulation of SLC7A11/xCT creates a vulnerability to selenocystine-induced cytotoxicity.

The SLC7A11/xCT cystine and glutamate antiporter has emerged as an attractive target for cancer therapy due to its selective overexpression in multiple cancers and its role in preventing ferroptosis. Utilizing pharmacological and genetic approaches in hepatocellular carcinoma cell lines, we demonstrate that overexpression of SLC7A11 engenders hypersensitivity towards l-selenocystine, a naturally occurring diselenide that bears close structural similarity to l-cystine. We find that the abundance of SLC7A11 positively correlates with sensitivity to l-selenocystine, but surprisingly, not to Erastin, an inhibitor of SLC7A11 activity. Our data indicate that SLC7A11 acts as a transport channel for l-selenocystine, which preferentially incites acute oxidative stress and damage eventuating to cell death in cells that highly express SLC7A11. Hence, our findings raise the prospect of l-selenocystine administration as a novel strategy for targeting cancers that up-regulate SLC7A11 expression.

Knotted lanugo in a newborn: Cultural practices revealed.

Across the world, there are varied cultural practices applied in the newborn period that pediatric dermatologists need to be familiar with. This report details a 9-day-old girl who presented with black, spike-like hairs across the back after her mother had been rubbing breast milk on her back in a circular motion for the first 7 days of life. On dermatoscopic exam, these lesions were found to be tight bundles of lanugo hairs, consistent with a diagnosis of knotted lanugo. Improved understanding of cultural practices and newborn skin care routines is critical for diagnosis, treatment, and counseling.

Second primary malignancies after ocular adnexal lymphoma diagnosis.

BACKGROUND: Although studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated this risk in patients with lymphoma originating within the ocular adnexa. We conducted a retrospective study to assess incidence of secondary malignancies in patients with a prior diagnosis of ocular adnexal lymphoma (OAL) and to determine latency periods and age-groups at increased risk for SPM occurrence. METHODS: Retrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results (SEER) 9 database. Patients with an initial primary malignancy diagnosis of OAL between 1973 and 2015 were included in the study. Standardized incidence ratios (SIR) and excess absolute risks (EAR) compared to a SEER reference population with similar sex, race, age, and calendar year were computed for SPMs. Excess absolute risk is per 10,000 individuals; alpha of 0.05 was used. RESULTS: Of 1834 patients with primary ocular adnexal lymphoma, 279 developed a secondary malignancy during average follow-up of 110.03 months (+/- 88.46), denoting higher incidence than expected (SIR 1.20; 95% CI, 1.07 to 1.35; EAR 30.56). Amongst the primary lymphoma cohort, 98.7% (1810/1834) of patients had non-Hodgkin's lymphoma and amongst those that developed secondary malignancies, 99.6% (278/279) had non-Hodgkin's lymphoma. Patients exhibited increased incidence of lymphohematopoietic and non-lymphohematopoietic second malignancies and no secondary malignancies of the eye or orbit. Patients had increased incidence of secondary malignancies in the first year (SIR 2.07; 95% CI, 1.49 to 2.79; EAR 150.37) and 1-5 years following lymphoma diagnosis (SIR 1.24; 95% CI, 1.01 to 1.51; EAR 34.89). Patients with various OAL subtypes demonstrated differing patterns of site-specific and overall SPM risk. CONCLUSIONS: Patients with prior diagnosis of ocular adnexal lymphoma possess increased risk of hematologic and non-hematologic secondary malignancies. Risk of secondary malignancy could vary by lymphoma subtype. Patients with ocular adnexal lymphoma may benefit from regular surveillance to promote early detection of second primary malignancies.

Procalcitonin to Distinguish Viral From Bacterial Pneumonia: A Systematic Review and Meta-analysis.

Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37-.71; I2 = 95.5%) and 0.76 (95% CI, .62-.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP.

Treating Psoriasis With Halobetasol Propionate and Tazarotene Combination: A Review of Phase II and III Clinical Trials.

Objective: To review phase II and III clinical trial data to evaluate the efficacy and safety of the halobetasol propionate/tazarotene (HP/TAZ) combination lotion (Duobrii), a medication approved by the Food and Drug Administration in April 2019 for adults with plaque psoriasis. Data Sources: A systematic search (January 2005 to July 2019) of MEDLINE (PubMed) and EMBASE databases was performed using the terms halobetasol, tazarotene, halobetasol/tazarotene, Duobrii, and IDP-118. Study Selection and Data Extraction: Relevant English-language articles reporting on phase II and phase III clinical trials were included. Data from the individual trials were extracted independently and then cross-checked to ensure accuracy. Data Synthesis: HP/TAZ was safe and efficacious compared with HP alone, TAZ alone, or vehicle. More patients achieved treatment success, described as a ≥2-grade improvement on Investigator Global Assessment Scale, over 8 weeks of treatment and at the 4-week follow-up after treatment cessation. The most common adverse events were dermatitis, pain, and pruritus, which occurred more often in the TAZ groups compared with the HP/TAZ cohorts. Relevance to Patient Care and Clinical Practice: The once-daily HP/TAZ combination lotion simplifies psoriasis treatment and may facilitate adherence, which may improve psoriasis outcomes. Conclusions: HP/TAZ combination lotion is efficacious and safe for plaque psoriasis treatment, with more patients achieving end points and fewer side effects than in HP, TAZ, or vehicle-treated controls. Drug synergy may play a role. Importantly, patient adherence to a once-daily combinational therapy is likely to contribute to efficacy.

Efficacy of quality improvement and patient safety workshops for students: a pilot study.

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes. METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause Analysis (RCA), Plan-Do-Study-Act (PDSA) Cycles, Evidence Based Medicine (EBM), and Patient Handoffs. Each workshop included a hands-on component to engage learners in practical applications of QI/PS skills in their careers. Change in knowledge, attitudes, and behaviors was assessed via pre- and post-surveys using 5-point Likert scales, and analyzed using either the McNemar test or non-parametric Wilcoxon signed-rank test. Surveys also gathered qualitative feedback regarding strengths, future areas for improvement, and reasons for attending the workshops. RESULTS: Data was collected from 88.5% of learners (n = 185/209); 19.5% of learners reported prior formal instruction in these topics. Statistically significant improvements in learners' confidence were observed for each workshop. Additionally, after attending workshops, learners felt comfortable teaching the learned QI/PS skill to colleagues (mean pre/post difference 1.96, p < 0.0001, n = 139) and were more likely to pursue QI/PS projects in their careers (mean pre/post difference 0.45, p < 0.0001, n = 139). Lastly, learners demonstrated a statistically significant increase in knowledge in four out of five skills workshop topics. CONCLUSION: Few medical students have formal instruction in QI/PS tools. This pilot study highlights advantages of incorporating an innovative, student-directed modified 'flipped classroom' methodology, with a focus on active experiential learning and minimal didactic instruction.

Association between pemphigus and psoriasis: a systematic review and meta-analysis.

Pemphigus has been associated with other autoimmune and autoinflammatory disorders. Specifically, some case reports in the literature document coexistence of pemphigus with psoriasis, but this association is lacking larger scale investigation. With this in mind, we conducted a systematic review and meta-analysis to evaluate the association between pemphigus and psoriasis. In doing so, we found an association between the two conditions. Pemphigus was more common in patients with psoriasis than in controls (OR 2.64, 95% CI 1.24-5.59, P=0.01), with heterogeneity (I2=94%). We go on to propose pathophysiologic mechanisms and its relevance for diagnostic and management considerations.

Does it match? Analyzing self-reported online dermatology match data to Charting Outcomes in the Match.

Dermatology is arguably the most competitive residency (81.6% match rate for United States allopathic seniors) with significantly more applicants than available positions. To objectify this process, the National Residency Match Program (NRMP) has produced bi-annual Charting Outcomes in Match (COM) datasets, which aggregate data from the prior two application cycles and tabulate statistics to aid applicants. In parallel, online forums provide medical trainees with vast amounts of information, including residency application insights. Reddit medical school subforum compiles annual spreadsheets of anonymous, individualized applicant data to aid future applicants. We compared this data to NRMP data to show that although the data means are similar (e.g. Step 1), the Reddit dermatology spreadsheet collects more data and the individualized nature aids applicants in a personalized way unlike the mean aggregate data in NRMP. Under univariate analysis, Alpha Omega Alpha status, overall publications, and dermatology-specific publications are associated with interview invitation rates. Although limitations of the study include small data size and reporting bias, this is the first of its kind to our knowledge to compare these two often-used tools to aid dermatology applicants. Future endeavors should expand anonymous data reporting and use the data to carry out more extensive studies to investigate factors influencing the application process.

Methotrexate for alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Methotrexate has been used both as monotherapy and as an adjunct to corticosteroids in the treatment of alopecia areata (AA), though there exists a paucity of definitive evidence and guidelines in this setting. OBJECTIVES: To 1) determine the efficacy and risks associated with methotrexate therapy for AA, 2) determine the differences in efficacy of combination (methotrexate plus corticosteroids) versus stand-alone (methotrexate) treatment, and 3) determine the relative efficacy of methotrexate in adult versus pediatric populations. METHODS: A systematic review and meta-analysis was performed according to recommended PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] guidelines. RESULTS: Methotrexate has reasonable effectiveness in patients with severe AA; adults appear to be more responsive to methotrexate treatment than pediatric patients. Combination treatment results in a higher complete response rate than methotrexate stand-alone treatment. A large proportion of patients had recurrence in the setting of tapering treatment. Complication rates were acceptable and similar between adult and pediatric patients. LIMITATIONS: The studies reviewed were retrospective observational studies with heterogeneity between centers in terms of methotrexate dosages and protocols in use for AA, and there was a lack of data beyond 1 year for the adjunctive treatments. CONCLUSION: Methotrexate is an effective monotherapy or adjunct therapy in combination with corticosteroids in the treatment of severe AA.

Systemic contact dermatitis related to alcoholic beverage consumption.

Systemic contact dermatitis is a rash secondary to systemic exposure to allergens after sensitization. Numerous agents are implicated including Balsam of Peru, a plant-derived compound often used for flavoring and fragrance. Alcoholic beverages can contain many possible allergens, including cinnamon, vanilla, citrus peels, and Balsam of Peru. Herein, we describe two patients presenting with recurrent, diffuse, erythematous, and pruritic cutaneous eruptions suspicious for contact dermatitis. Based on clinical history, exam, and formal and at-home patch testing results, we believe the most likely etiology was Balsam of Peru within the alcohol beverages leading to systemic contact dermatitis. Both patients markedly improved after avoidance of their alcoholic beverages. Overall, systemic contact dermatitis secondary to alcohol consumption is a rare phenomenon, whereas Balsam of Peru is a relatively common allergen. Suspicion must be high to identify possible allergens (including Balsam of Peru) exposure within alcoholic beverages such as artificial flavorings, aromas, and mixtures.

Diagnosis of cutaneous T-cell lymphoma by insurance type before and after the Affordable Care Act: a national database study.

The Affordable Care Act (ACT) was implemented to increase health care access and reduce the uninsured in the age group between pediatric and Medicare populations (18-64). The association of the ACA with insurance type upon diagnosis (uninsured, Medicaid, non-Medicaid) has been investigated for otolaryngologic, gynecologic, and the top five non-skin malignancies. Such studies for cutaneous malignancies are lacking. We conducted a retrospective analysis of the prospective National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer database to assess the impact of the ACA on new diagnoses of cutaneous T-cell lymphoma (CTCL) by insurance type. Unlike prior studies of other malignancies, we did not observe significant differences between rate of diagnosis of CTCL by insurance type before and after full implementation of the ACA in all states, expansion states, and non-expansion states. Skin cancers do not have screening guidelines and CTCL is an uncommon malignancy, both of which may contribute to these findings. However, Medicaid-expansion states were much closer to reducing the percentage of newly diagnosed uninsured patients with CTCL than non-expansion states. As such, it may be prudent to investigate intrinsic socioeconomic barriers to care in Medicaid patients to improve their access to care to decrease the uninsured population and improve outcomes.

Corrigendum: Systemic contact dermatitis related to alcoholic beverage consumption.

The original article was published on September 15, 2019 and corrected on November 15, 2019.The revised version of the article adds a missing author. This change appears in the revised online PDF copy of this article.

Towards an Online Seizure Advisory System-An Adaptive Seizure Prediction Framework Using Active Learning Heuristics.

In the last decade, seizure prediction systems have gained a lot of attention because of their enormous potential to largely improve the quality-of-life of the epileptic patients. The accuracy of the prediction algorithms to detect seizure in real-world applications is largely limited because the brain signals are inherently uncertain and affected by various factors, such as environment, age, drug intake, etc., in addition to the internal artefacts that occur during the process of recording the brain signals. To deal with such ambiguity, researchers transitionally use active learning, which selects the ambiguous data to be annotated by an expert and updates the classification model dynamically. However, selecting the particular data from a pool of large ambiguous datasets to be labelled by an expert is still a challenging problem. In this paper, we propose an active learning-based prediction framework that aims to improve the accuracy of the prediction with a minimum number of labelled data. The core technique of our framework is employing the Bernoulli-Gaussian Mixture model (BGMM) to determine the feature samples that have the most ambiguity to be annotated by an expert. By doing so, our approach facilitates expert intervention as well as increasing medical reliability. We evaluate seven different classifiers in terms of the classification time and memory required. An active learning framework built on top of the best performing classifier is evaluated in terms of required annotation effort to achieve a high level of prediction accuracy. The results show that our approach can achieve the same accuracy as a Support Vector Machine (SVM) classifier using only 20 % of the labelled data and also improve the prediction accuracy even under the noisy condition.

Potential of Wake-Up Radio-Based MAC Protocols for Implantable Body Sensor Networks (IBSN)-A Survey.

With the advent of nano-technology, medical sensors and devices are becoming highly miniaturized. Consequently, the number of sensors and medical devices being implanted to accurately monitor and diagnose a disease is increasing. By measuring the symptoms and controlling a medical device as close as possible to the source, these implantable devices are able to save lives. A wireless link between medical sensors and implantable medical devices is essential in the case of closed-loop medical devices, in which symptoms of the diseases are monitored by sensors that are not placed in close proximity of the therapeutic device. Medium Access Control (MAC) is crucial to make it possible for several medical devices to communicate using a shared wireless medium in such a way that minimum delay, maximum throughput, and increased network life-time are guaranteed. To guarantee this Quality of Service (QoS), the MAC protocols control the main sources of limited resource wastage, namely the idle-listening, packet collisions, over-hearing, and packet loss. Traditional MAC protocols designed for body sensor networks are not directly applicable to Implantable Body Sensor Networks (IBSN) because of the dynamic nature of the radio channel within the human body and the strict QoS requirements of IBSN applications. Although numerous MAC protocols are available in the literature, the majority of them are designed for Body Sensor Network (BSN) and Wireless Sensor Network (WSN). To the best of our knowledge, there is so far no research paper that explores the impact of these MAC protocols specifically for IBSN. MAC protocols designed for implantable devices are still in their infancy and one of their most challenging objectives is to be ultra-low-power. One of the technological solutions to achieve this objective so is to integrate the concept of Wake-up radio (WuR) into the MAC design. In this survey, we present a taxonomy of MAC protocols based on their use of WuR technology and identify their bottlenecks to be used in IBSN applications. Furthermore, we present a number of open research challenges and requirements for designing an energy-efficient and reliable wireless communication protocol for IBSN.