Idiopathic Facial Aseptic Granuloma in an older child: A case report in a pre-adolescent boy.

Idiopathic facial aseptic granuloma (IFAG) is an uncommon, benign lesion that presents in the pediatric population. The diagnosis is classically associated with preschool-aged children. Herein, we present a case of IFAG in a pre-adolescent boy, emphasizing the importance of diagnostic consideration in older children.

Effect of the Adoption of a Comprehensive Electronic Health Record on Graduate Medical Education: Perceptions of Faculty and Trainees.

OBJECTIVES: Health systems are adopting electronic health records (EHRs). There are few studies on the effects of EHR implementation on graduate medical education. The authors sought to longitudinally assess perceptions of the impact of EHRs on graduate medical education during implementation and 2 years after implementation. METHODS: A survey was distributed to faculty and trainees during the first year (2013) of adoption of the EHR system. A follow-up survey was distributed 2 years later (2015). The χ2 test was used to compare the quantitative responses, and factor analysis was conducted to identify correlations between items. Free text responses were analyzed qualitatively. RESULTS: The initial survey (in 2013) included 290 faculty and 106 trainees; the follow-up survey (in 2015) included 353 faculty and 226 trainees. In 2013, respondents had a positive impression of EHRs. During the implementation phase, participants believed that face-to-face teaching was negatively affected (P = 0.001). Faculty believed EHRs had a negative effect on trainees' ability to take a history/conduct physical examinations (P = 0.002) and to formulate a differential diagnosis/plan independently (P = 0.003). In 2015, faculty opinions of the impact of the EHR remained unchanged; trainee responses were more positive than in 2013 in some areas. Qualitative analysis showed that the most frequent strategies to enhance the educational process were the development of EHR skills and improved chart access and note assistance. CONCLUSIONS: Respondents remain positive about the EHR 2 years after implementation. Faculty remain concerned about its effect on the educational process, whereas residents appear more positive regarding the potential for EHRs to enhance their education.

Concurrent pyogenic granuloma and bullous impetigo of a pregnant woman's finger.

BACKGROUND: Bullous impetigo is a superficial skininfection caused by Staphylococcus aureus (S.aureus). Pyogenic granuloma is a common benigntumor frequently associated with prior trauma.Bullous impetigo and pyogenic granuloma may occurin pregnant women. PURPOSE: The features of a pregnant womanwith pyogenic granuloma and bullous impetigoconcurrently present in a lesion on her finger aredescribed. METHODS: PubMed was used to search the followingterms: bullous impetigo, pregnancy, and pyogenicgranuloma. All papers were reviewed; relevantarticles, along with their references, were evaluatedResults: A red ulcerated nodule with a collaretteof epithelium around the tumor and surroundingbullae appeared on the fifth digit of the left hand of a31-year-old woman who was at 36 weeks gestation. Abacterial culture grew methicillin sensitive S. aureus.An excisional biopsy was performed. Histologicfindings revealed not only a benign vascular tumorwith an infiltrate of mixed inflammatory cells, butalso an intraepidermal blister. She received oralantibiotics and there was complete resolution of thefinger lesion and infection with preservation of digitfunction. CONCLUSION: Albeit uncommon, pyogenic granulomaand bullous impetigo may concurrently occur in thesame lesion. Therapeutic intervention should focuson treating both the benign skin tumor and theinfection.

Further characterization of Cys-type and Ser-type anaerobic sulfatase maturating enzymes suggests a commonality in the mechanism of catalysis.

The anaerobic sulfatase-maturating enzyme from Clostridium perfringens (anSMEcpe) catalyzes the two-electron oxidation of a cysteinyl residue on a cognate protein to a formylglycyl residue (FGly) using a mechanism that involves organic radicals. The FGly residue plays a unique role as a cofactor in a class of enzymes termed arylsulfatases, which catalyze the hydrolysis of various organosulfate monoesters. anSMEcpe has been shown to be a member of the radical S-adenosylmethionine (SAM) family of enzymes, [4Fe-4S] cluster-requiring proteins that use a 5'-deoxyadenosyl 5'-radical (5'-dA(•)) generated from a reductive cleavage of SAM to initiate radical-based catalysis. Herein, we show that anSMEcpe contains in addition to the [4Fe-4S] cluster harbored by all radical SAM (RS) enzymes, two additional [4Fe-4S] clusters, similar to the radical SAM protein AtsB, which catalyzes the two-electron oxidation of a seryl residue to a FGly residue. We show by size-exclusion chromatography that both AtsB and anSMEcpe are monomeric proteins, and site-directed mutagenesis studies of AtsB reveal that individual Cys → Ala substitutions at seven conserved positions result in an insoluble protein, consistent with those residues acting as ligands to the two additional [4Fe-4S] clusters. Ala substitutions at an additional conserved Cys residue (C291 in AtsB and C276 in anSMEcpe) afford proteins that display intermediate behavior. These proteins exhibit reduced solubility and drastically reduced activity, behavior that is conspicuously similar to that of a critical Cys residue in BtrN, another radical SAM dehydrogenase [Grove, T. L., et al. (2010) Biochemistry 49, 3783-3785]. We also show that wild-type anSMEcpe acts on peptides containing other oxidizable amino acids at the target position. Moreover, we show that the enzyme will convert threonyl peptides to the corresponding ketone product, and also allo-threonyl peptides, but with a significantly reduced efficiency, suggesting that the pro-S hydrogen atom of the normal cysteinyl substrate is stereoselectively removed during turnover. Lastly, we show that the electron generated during catalysis by AtsB and anSMEcpe can be utilized for multiple turnovers, albeit through a reduced flavodoxin-mediated pathway.

Identification and functional characterization of rare mutations of the neuroligin-2 gene (NLGN2) associated with schizophrenia.

Schizophrenia is a severe chronic mental disorder with a high genetic component in its etiology. Several lines of study have suggested that synaptic dysfunction may underlie the pathogenesis of schizophrenia. Neuroligin proteins function as cell-adhesion molecules at post-synaptic membrane and play critical roles in synaptogenesis and synaptic maturation. In this study, we systemically sequenced all the exons and promoter region of neuroligin-2 (NLGN2) gene in a sample of 584 schizophrenia patients and 549 control subjects from Taiwan. In total, we identified 19 genetic variants, including six rare missense mutations such as R215H (one patient), V510M (two patients), R621H (one patient), A637T (two patients), P800L (one patient and one control) and A819S (one patient and one control). In silico analysis predicted that two patient-specific missense mutations, R215H and R621H, had damaging effect, whereas the other missense mutations were benign. Importantly, functional analysis with immunocytochemistry and electrophysiological recordings identified the R215H mutant as a loss-of-function mutant in inducing GABAergic synaptogenesis. Mechanistically, the synaptogenic deficiency of R215H mutant was due to its retention inside the endoplasmic reticulum and inability to be transported to cell membrane. Our study suggests that defects in GABAergic synapse formation in the brain may be an important contributing factor for the onset of schizophrenia. In the family study of this mutation, we found his elder brother also carried this mutation but did not have psychiatric symptoms, indicating that this mutation has incomplete penetrance, and thus the clinical relevance of this mutation should be interpreted with caution.

A systematic review of satisfaction with teledermatology.

Background The two most commonly used modalities of teledermatology (TD) are store-and-forward (SF) and live-interactive (LI) TD. Existing studies have not compared these tools with respect to patient and provider satisfaction. Objective To systematically review all published studies of patient and provider satisfaction with SF and LI TD. Methods PubMed, EMBASE, and Cochrane databases were systematically searched for studies on provider or patient satisfaction with SF or LI TD between January 2000 and June 2016. Results Forty eligible studies were identified: 32 with SF TD, 10 with LI TD, and 2 evaluating both. With SF TD, 96% of studies assessing patient satisfaction and 82% of studies assessing provider satisfaction demonstrated satisfaction ( n = 24 and 17, respectively). With LI TD, 89% of studies assessing patient satisfaction and all studies assessing provider satisfaction revealed satisfaction (n = 9 and 6, respectively). Conclusion Patients and providers are satisfied with both SF and LI TD. Studies assessing satisfaction with LI have not been conducted in recent years, and have only been conducted in limited geographic patient populations. Further research assessing satisfaction with TD will help address any dissatisfaction with its uses and allow for increased support and funding of future programmes.

Bridging the Gap: Identifying Global Trends in Gender Disparity Among the Radiology Physician Workforce.

RATIONALE AND OBJECTIVES: Women make up half of American medical school graduates, but remain underrepresented among radiologists. This study sought to determine whether workforce gender disparities exist in other countries, and to identify any country-specific indices associated with increased female representation. MATERIALS AND METHODS: In this cross-sectional study, 95 professional radiology organizations in 75 countries were contacted via email to provide membership statistics, including proportion of female members, female members aged 35 or under, and women in society leadership positions. Country-specific metrics collected included gross domestic product, Gini index, percent female medical school enrollment, and Gender Development Index for the purposes of univariate multiple regression analysis. RESULTS: Twenty-nine organizations provided data on 184,888 radiologists, representing 26 countries from Europe (n = 12), North America (n = 2), Central/South America (n = 6), Oceania (n = 2), Asia (n = 3), and Africa (n = 1) for a response rate of 34.7% (26/75). Globally, 33.5% of radiologists are female. Women constitute a higher proportion of younger radiologists, with 48.5% of radiologists aged 35 or under being female. Female representation in radiology is lowest in the United States (27.2%), highest in Thailand (85.0%), and most variable in Europe (mean 40.1%, range 28.8%-68.9%). The proportion of female radiologists was positively associated with a country's Gender Development Index (P = .006), percent female medical student enrollment (P = .001), and Gini index (P = .002), and negatively associated with gross domestic product (P = .03). CONCLUSIONS: Women are underrepresented in radiology globally, most notably in the United States. Countries with greater representation of women had higher gender equality and percent female medical school enrollment, suggesting these factors may play a role in the gender gap.

Diagnostic Criteria of Ulcerative Pyoderma Gangrenosum: A Delphi Consensus of International Experts.

Importance: Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a "diagnosis of exclusion," a definition not compatible with clinical decision making or inclusion for clinical trials. Objective: To propose and validate diagnostic criteria for ulcerative pyoderma gangrenosum. Evidence Review: Diagnostic criteria were created following a Delphi consensus exercise using the RAND/UCLA Appropriateness Method. The criteria were validated against peer-reviewed established cases of pyoderma gangrenosum and mimickers using k-fold cross-validation with methods of multiple imputation. Findings: Delphi exercise yielded 1 major criterion-biopsy of ulcer edge demonstrating neutrophilic infiltrate-and 8 minor criteria: (1) exclusion of infection; (2) pathergy; (3) history of inflammatory bowel disease or inflammatory arthritis; (4) history of papule, pustule, or vesicle ulcerating within 4 days of appearing; (5) peripheral erythema, undermining border, and tenderness at ulceration site; (6) multiple ulcerations, at least 1 on an anterior lower leg; (7) cribriform or "wrinkled paper" scar(s) at healed ulcer sites; and (8) decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Receiver operating characteristic analysis revealed that 4 of 8 minor criteria maximized discrimination, yielding sensitivity and specificity of 86% and 90%, respectively. Conclusions and Relevance: This Delphi exercise produced 1 major criterion and 8 minor criteria for the diagnosis of ulcerative pyoderma gangrenosum. The criteria may serve as a guideline for clinicians, allowing for fewer misdiagnoses and improved patient selection for clinical trials.

Oral mucosa biology and salivary biomarkers.

Although the surfaces of both the skin and oral mucosa are protected by squamous epithelial cells and fall within the scope of dermatologic practice, the oral cavity contains highly specialized structures and functions distinct from other skin biology and pathologic conditions and are also the purview of clinicians who care for patients with skin and mucosal diseases. We describe the distinct features of the tongue, mucosa, and salivary glands. In particular, we examine the composition and function of the saliva, with special focus on salivary biomarkers. Within the oral cavity, saliva shows great promise as a noninvasive and sensitive marker for many systemic diseases. Biomarkers are being used as diagnostic or monitoring tools for a wide variety of diseases, including systemic lupus erythematosus, Sjögren disease, Behçet disease, and autoimmune blistering disorders, as well as premalignant and malignant lesions of the mouth.

Chemoprevention of Keratinocyte Carcinomas: An Updated Review.

A well-established link between ultraviolet exposure and the carcinogenesis of keratinocyte carcinomas exists. Despite increased sun protection efforts, skin cancer remains the most common cancer in the USA. Numerous studies on the topic of chemoprevention investigate alternative topical, oral, and injectable agents to reduce skin cancer incidence in those at risk. Such agents include sunscreen, numerous vitamins and minerals, difluoromethylornithine, non-steroidal anti-inflammatory drugs, various peptides, field therapy, statins, and polyphenols. In this focused review, we discuss the risks and benefits of chemoprotective agents reported in clinical studies conducted in humans. We report several agents that may reduce skin cancer incidence in those at risk.

Outcomes and toxicity of stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab.

PURPOSE: Patients with melanoma treated with ipilimumab and radiosurgery (stereotactic radiosurgery [SRS]) were reviewed for efficacy/safety. METHODS: Patients who received ipilimumab and SRS for brain metastases were analyzed for control of SRS-treated metastasis and overall survival. RESULTS: We identified 27 patients, 26 were assessable for outcomes. Median time-to-treated metastasis progression was 6.3 months (95% CI: 3.1-12.2). Overall survival was 23.4 months (95% CI: 5.7-not estimable) for SRS prior to/during ipilimumab (n = 14), and 10.4 months (95% CI: 1.9-not estimable) for SRS after ipilimumab (n = 12). Overall, no unexpected toxicities were seen: 11% of patients experienced grade 3 CNS toxicity and 7% developed radionecrosis. CONCLUSION: SRS for melanoma brain metastases with ipilimumab was well-tolerated. There may be improved survival for patients receiving SRS prior to/during ipilimumab.

Primary and Secondary Chemoprevention of Malignant Melanoma.

The incidence of malignant melanoma (MM) continues to rise in the United States. While sun protection and full body skin examinations remain the mainstay of preventative care, chemoprevention of the deadly disease has become an increasingly popular field of study. In this focused review, we discuss current findings and analyze the risks and benefits of various agents investigated for the primary and secondary chemoprevention of MM. Such agents include topical retinoids, vitamins, and supplements, Polypodium leucotomas extracts, non-steroidal anti-inflammatory agents (NSAIDs), statins, sunscreens, and field therapy with topical imiquimod for primary and secondary chemoprevention. We further identify a need for expanded high quality human research on the topic.

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab.

PURPOSE: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. METHODS AND MATERIALS: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. RESULTS: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non-immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non-statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. CONCLUSIONS: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.

Report of ipilimumab in a heart transplant patient with metastatic melanoma on tacrolimus.

Ipilimumab is the first immunotherapy shown to increase overall survival in patients with metastatic melanoma. Currently, there are no accepted guidelines for use of ipilimumab in organ transplant patients. There is only one report in the literature on successful administration of ipilimumab in two kidney transplant recipients. In this report, a heart transplant patient with metastatic melanoma was successfully treated with ipilimumab. He experienced no adverse drug reactions. However, after standard treatment with regimen of four doses at 3 mg/kg, he experienced disease progression. Here, we address concerns of organ rejection or ineffective treatment when using ipilimumab or other immune checkpoint inhibitors in patients who are chronically immunosuppressed.

Reliability of a telemedicine system designed for rural Kenya.

OBJECTIVE: Access to health care in rural areas of developing nations is hindered by both the lack of physicians and the preference of many physicians to practice in urban settings. As a result, rural patients often choose not to sacrifice wages or time to visit distant health care providers. A telemedicine system, Mashavu: Networked Health Solutions, designed to increase access to preprimary health care in rural areas, was field-tested in rural Kenya. This study aims to examine the reliability of the system compared to the traditional face-to-face method of health care delivery. METHOD: Reliability of the telemedicine system was tested using a modified intraobserver concordance study. Community health workers operated the system in various remote locations. Patient health information including chief complaint, medical history, and vital statistics were sent via Internet to a consulting nurse. After patients completed the telemedicine consultation, they also met in-person with the same nurse. Subsequently, the nurse's advice during the in-person session was compared with his feedback provided through the telemedicine consultation. RESULTS: When comparing the nurse's advice given through the telemedicine system with the advice given through more traditional face-to-face, in-person consultation, the nurse provided consistent medical feedback in 78.4% of the cases (n = 102). The nurse's advice regarding patient action (eg, clinical referrals or no further care necessary) was the same in 89.2% of the cases (n = 91). CONCLUSION: The study found that this telemedicine system was able to provide patients with approximately the same quality of care and advice as if the patient had physically travelled to a clinic to see a nurse. In rural areas of developing nations where there are high logistical and economical barriers to accessing health care, this telemedicine system successfully increased the ease and lowered the cost of connecting rural patients with nurses to provide preprimary care.