Factors Associated With Patient-Initiated Communication After Mohs Micrographic Surgery.

BACKGROUND: Despite extensive counseling, patients commonly call with postoperative concerns after Mohs micrographic surgery (MMS). OBJECTIVE: We sought to determine the incidence, reasons, and patient and surgical characteristics that lead to patient-initiated communication after MMS. MATERIALS AND METHODS: A retrospective chart review of 1,531 patients who underwent MMS during the observational period was conducted. Demographics and perioperative characteristics of patients who initiated communication were compared with a random sample of matched controls. RESULTS: Of the 1,531 patients who underwent MMS, 263 patients (17.2%) initiated 412 communication encounters within 90 days of surgery. Top reasons for patient-initiated communication included wound concerns, bleeding, and postoperative pain. Female patients and those with a larger surgical defect size (cm) were more likely to call postoperatively. Patients who underwent second intention healing, grafts, and interpolation flaps were more likely to initiate communication compared to patients repaired with a linear closure. CONCLUSION: This study identifies the incidence, reasons, and patient and surgical factors predictive of patient-initiated communication after MMS, which may allow for targeted improvements in postoperative counseling, ameliorating patient anxiety, augmenting patient satisfaction, and improved efficiency for the health care team.

Integrating The Integrated Skin Exam film into medical education.

AbstractBackgroundThe mortality rate for melanoma continues to rise and the greatest improvement in melanoma survival is attributable to early detection with skin cancer screening exams. However, physicians feel that limited training in the examination of skin and limited clinical time both serve as barriers to adequately assess high-risk lesions.ObjectiveTo test the use of The Integrated Skin Exam film as an instructional tool to teach the examination of skin in a live classroom setting, outside of the purview of the original formal study.MethodsIdentical cross-sectional surveys were administered pre- and post-film to a class of first-year medical students at the time of viewing The Integrated Skin Exam film. Results were compared to the initial assessment of this film as a teaching tool in a research setting.ResultsOf the maximum 182 possible surveys administered, we collected 148 pre-surveys and 142 post-surveys (81.3% and 78.0% 33 response rates, respectively). After viewing the film, students showed improvement in identification of high-risk demographic 34 groups (79.3% vs 58.9%, p<0.001) and high-risk anatomic sites in both women (91.9% vs 59.6%, p<0.001) and men (92% vs 35 62.1%, p<0.001). Students demonstrated increased confidence in the skin cancer examination (SCE) (52.2% vs 6.9%, p<0.001) and a greater proportion (74.4% vs 48.3%, p<0.001) of students believed less than 3 minutes was required to integrate a skin cancer exam (SCE) into the routine examination.ConclusionsThe Integrated Skin Exam film is a valuable training tool as proven by increased knowledge of, and improved attitudes about the 2 SCE after viewing the film. In addition, there was a striking similarity in outcomes when using this film in a live classroom 3 environment compared to the original study setting.

Dermatology Interest Groups in Medical Schools.

Involvement in a Dermatology Interest Group (DIG) allows students to learn about dermatology, partake in service projects, get involved in research, and ask questions about the application process for residency programs. In this article, we review the activities and member involvement of DIGs from 11 medical schools. To our knowledge, this is the first descriptive analysis of DIGs across the United States. This comparison of DIGs is not only potentially helpful for medical schools interested in establishing a DIG, but it also offers insight into how previously established DIGs could improve and have a greater impact both in individual medical schools and in the community at-large.

Benign subclinical syringomatous proliferations adjacent to a microcystic adnexal carcinoma: a tumor mimic with significant patient implications.

Microcystic adnexal carcinoma (MAC) is an uncommon, locally aggressive, malignant cutaneous tumor with pilar and eccrine differentiation. Mohs micrographic surgery is the treatment of choice for this condition, but specific histological findings can complicate MAC removal and leave doubt as to whether the tumor has been completely removed. Here we describe the clinical and pathological characteristics of a case in which a patient with an MAC underwent multiple reexcisions because of the presence of benign subclinical syringomatous proliferations adjacent to the primary lesion. Our case raises awareness of syringomatous proliferation, a benign process histologically similar but behaviorally distinct from a primary MAC. This experience highlights the importance of continued communication between dermatopathologists and dermatologic surgeons in providing quality patient care.

Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome.

IMPORTANCE: Hereditary factors play a key role in the risk of developing several cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and germline testing. OBJECTIVE: To examine the prevalence of pathogenic germline variants (PGVs) in patients with cancer using a universal testing approach compared with targeted testing based on clinical guidelines and the uptake of cascade family variant testing (FVT). DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study assessed germline genetic alterations among patients with solid tumor cancer receiving care at Mayo Clinic cancer centers and a community practice between April 1, 2018, and March 31, 2020. Patients were not selected based on cancer type, disease stage, family history of cancer, ethnicity, or age. EXPOSURES: Germline sequencing using a greater than 80-gene next-generation sequencing platform. MAIN OUTCOMES AND MEASURES: Proportion of PGVs detected with a universal strategy compared with a guideline-directed approach and uptake of cascade FVT in families. RESULTS: A total of 2984 patients (mean [SD] age, 61.4 [12.2] years; 1582 [53.0%] male) were studied. Pathogenic germline variants were found in 397 patients (13.3%), including 282 moderate- and high-penetrance cancer susceptibility genes. Variants of uncertain significance were found in 1415 patients (47.4%). A total of 192 patients (6.4%) had incremental clinically actionable findings that would not have been detected by phenotype or family history-based testing criteria. Of those with a high-penetrance PGV, 42 patients (28.2%) had modifications in their treatment based on the finding. Only younger age of diagnosis was associated with presence of PGV. Only 70 patients (17.6%) with PGVs had family members undergoing no-cost cascade FVT. CONCLUSIONS AND RELEVANCE: This prospective, multicenter cohort study found that universal multigene panel testing among patients with solid tumor cancer was associated with an increased detection of heritable variants over the predicted yield of targeted testing based on guidelines. Nearly 30% of patients with high-penetrance variants had modifications in their treatment. Uptake of cascade FVT was low despite being offered at no cost.

Gardner-Diamond syndrome: a systematic review of treatment options for a rare psychodermatological disorder.

Gardner-Diamond syndrome (GDS) is a rare psychodermatological condition characterized by the formation of spontaneous, painful skin lesions that develop into ecchymosis following episodes of severe physiological or psychological stress. The majority of GDS cases occur in young adult females, and although the etiology of this rare disorder is unknown, there appears to be a psychological component correlated with the coexistence of previous psychiatric diagnoses. Due to the rare nature of this disorder, there exist few guidelines for prompt clinical diagnosis and optimal treatment. Here, a systematic review was conducted to include 45 cases of patients with GDS to better understand clinical presentation as well as current treatment options. Ultimately, GDS is a diagnosis of exclusion after other coagulopathies and causes of purpura are ruled out. High clinical suspicion following laboratory and clinical exclusion of known physiological causes is necessary for diagnosis. Selective serotonin reuptake inhibitors (SSRIs) and corticosteroids are cost effective first line treatments for GDS with proven efficacy in symptomatic relief. GDS refractory to initial treatment may require regular psychotherapy and titrated SSRI dosages to achieve long-term success. This review of available case studies serves to comprehensively describe the clinical presentation and available treatment approaches to this rare psychodermatological disorder.

A validated method for the quantitation of 1,1-difluoroethane using a gas in equilibrium method of calibration.

1,1-Difluoroethane (DFE), also known as Freon 152A, is a member of a class of compounds known as halogenated hydrocarbons. A number of these compounds have gained notoriety because of their ability to induce rapid onset of intoxication after inhalation exposure. Abuse of DFE has necessitated development of methods for its detection and quantitation in postmortem and human performance specimens. Furthermore, methodologies applicable to research studies are required as there have been limited toxicokinetic and toxicodynamic reports published on DFE. This paper describes a method for the quantitation of DFE using a gas chromatography-flame-ionization headspace technique that employs solventless standards for calibration. Two calibration curves using 0.5 mL whole blood calibrators which ranged from A: 0.225-1.350 to B: 9.0-180.0 mg/L were developed. These were evaluated for linearity (0.9992 and 0.9995), limit of detection of 0.018 mg/L, limit of quantitation of 0.099 mg/L (recovery 111.9%, CV 9.92%), and upper limit of linearity of 27,000.0 mg/L. Combined curve recovery results of a 98.0 mg/L DFE control that was prepared using an alternate technique was 102.2% with CV of 3.09%. No matrix interference was observed in DFE enriched blood, urine or brain specimens nor did analysis of variance detect any significant differences (alpha = 0.01) in the area under the curve of blood, urine or brain specimens at three identical DFE concentrations. The method is suitable for use in forensic laboratories because validation was performed on instrumentation routinely used in forensic labs and due to the ease with which the calibration range can be adjusted. Perhaps more importantly it is also useful for research oriented studies because the removal of solvent from standard preparation eliminates the possibility for solvent induced changes to the gas/liquid partitioning of DFE or chromatographic interference due to the presence of solvent in specimens.

High-dimensional regression analysis links magnetic resonance imaging features and protein expression and signaling pathway alterations in breast invasive carcinoma.

BACKGROUND: Imaging features derived from MRI scans can be used for not only breast cancer detection and measuring disease extent, but can also determine gene expression and patient outcomes. The relationships between imaging features, gene/protein expression, and response to therapy hold potential to guide personalized medicine. We aim to characterize the relationship between radiologist-annotated tumor phenotypic features (based on MRI) and the underlying biological processes (based on proteomic profiling) in the tumor. METHODS: Multiple-response regression of the image-derived, radiologist-scored features with reverse-phase protein array expression levels generated association coefficients for each combination of image-feature and protein in the RPPA dataset. Significantly-associated proteins for features were analyzed with Ingenuity Pathway Analysis software. Hierarchical clustering of the results of the pathway analysis determined which features were most strongly correlated with pathway activity and cellular functions. RESULTS: Each of the twenty-nine imaging features was found to have a set of significantly correlated molecules, associated biological functions, and pathways. CONCLUSIONS: We interrogated the pathway alterations represented by the protein expression associated with each imaging feature. Our study demonstrates the relationships between biological processes (via proteomic measurements) and MRI features within breast tumors.

OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers.

The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can "hijack" the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment.

Assessing free and total morphine following heroin overdose when complicated by the presence of toxic amitriptyline levels.

A 43-year-old female was reported to inject heroin, which led to her rapid death. Because of the potential for criminal charges, laboratory results that could verify "hotshot" heroin overdose were valuable. Initial toxicological analysis detected morphine (0.78 mg/L), amitriptyline (2.91 mg/L), and nortriptyline (2.80 mg/L) in femoral blood. Because these tricyclic antidepressant levels alone might normally be associated with a fatal outcome, the ratio of free versus total morphine (88.6%) and presence of 6-monoacetylmorphine in vitreous fluid were used support a history of rapid death following intravenous (IV) administration. The distribution of amitriptyline and nortriptyline was consistent with accumulation of drug after chronic dosing. Our other results suggest that the low morphine level in vitreous humor fluid (0.16 mg/L) relative to free morphine in femoral blood (0.78 mg/L) may also be an indicator of limited survival time following exposure to morphine. Based upon comprehensive toxicologic analysis, we determined overdose due to IV abuse of heroin was likely to have precipitated the fatal outcome. This case underscores the need for complete toxicologic workup and to consider individual variation in the dose response during toxicologic interpretation of postmortem results.

Multiple-response regression analysis links magnetic resonance imaging features to de-regulated protein expression and pathway activity in lower grade glioma.

BACKGROUND AND PURPOSE: Lower grade gliomas (LGGs), lesions of WHO grades II and III, comprise 10-15% of primary brain tumors. In this first-of-a-kind study, we aim to carry out a radioproteomic characterization of LGGs using proteomics data from the TCGA and imaging data from the TCIA cohorts, to obtain an association between tumor MRI characteristics and protein measurements. The availability of linked imaging and molecular data permits the assessment of relationships between tumor genomic/proteomic measurements with phenotypic features. MATERIALS AND METHODS: Multiple-response regression of the image-derived, radiologist scored features with reverse-phase protein array (RPPA) expression levels generated correlation coefficients for each combination of image-feature and protein or phospho-protein in the RPPA dataset. Significantly-associated proteins for VASARI features were analyzed with Ingenuity Pathway Analysis software. Hierarchical clustering of the results of the pathway analysis was used to determine which feature groups were most strongly correlated with pathway activity and cellular functions. RESULTS: The multiple-response regression approach identified multiple proteins associated with each VASARI imaging feature. VASARI features were found to be correlated with expression of IL8, PTEN, PI3K/Akt, Neuregulin, ERK/MAPK, p70S6K and EGF signaling pathways. CONCLUSION: Radioproteomics analysis might enable an insight into the phenotypic consequences of molecular aberrations in LGGs.

Spatial habitats from multiparametric MR imaging are associated with signaling pathway activities and survival in glioblastoma.

Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity, impacting response to treatment and overall survival time of 12-15 months. To study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were analyzed to characterize tumor-derived spatial habitats for their relationship with outcome (overall survival) and to identify their molecular correlates (i.e., determine associated tumor signaling pathways correlated with imaging-derived habitat measurements). Tumor sub-regions based on four sequences (fluid attenuated inversion recovery, T1-weighted, post-contrast T1-weighted, and T2-weighted) were defined by automated segmentation. From relative intensity of pixels in the 3-dimensional tumor region, "imaging habitats" were identified and analyzed for their association to clinical and genetic data using survival modeling and Dirichlet regression, respectively. Sixteen distinct tumor sub-regions ("spatial imaging habitats") were derived, and those associated with overall survival (denoted "relevant" habitats) in glioblastoma patients were identified. Dirichlet regression implicated each relevant habitat with unique pathway alterations. Relevant habitats also had some pathways and cellular processes in common, including phosphorylation of STAT-1 and natural killer cell activity, consistent with cancer hallmarks. This work revealed clinical relevance of MRI-derived spatial habitats and their relationship with oncogenic molecular mechanisms in patients with GBM. Characterizing the associations between imaging-derived phenotypic measurements with the genomic and molecular characteristics of tumors can enable insights into tumor biology, further enabling the practice of personalized cancer treatment. The analytical framework and workflow demonstrated in this study are inherently scalable to multiple MR sequences.

A motor vehicle accident fatality involving the inhalation of 1,1-difluoroethane.

A 24-year-old female driver with a history of substance abuse was pronounced dead following a single car motor vehicle accident. A surviving front seat passenger witnessed the decedent inhaling "Dust Off" cleaner just prior to losing control of the vehicle. The propellant compound used in this product is the halogenated hydrocarbon 1,1-difluoroethane (DFE). Sealed autopsy specimens were examined for the presence and subsequent quantitation of DFE utilizing an Agilent 6850 gas chromatograph (GC)-flame-ionization detector. The levels of DFE obtained were as follows: 29.8 mg/L in femoral blood, 40.3 mg/L in pulmonary arterial blood, 85.6 mg/L in aortic blood, 79.9 mg/L in chest cavity blood, 21.2 mg/L in vitreous, 11.7 mg/kg in brain, 27.9 mg/kg in liver, 71.0 mg/L in urine, and 51.8 mg/total gastric contents. The presence of DFE was confirmed in the decedent's urine by injection on an Agilent 6890/5973 GC-mass spectrometer in full scan mode. This case presents a uniquely witnessed observation of the apparent impairing effects and consequences of the acute inhalation of halogenated hydrocarbons such as DFE and the operation of a motor vehicle. The proximity of time of death to inhalant use may also provide insight to postmortem distribution patterns of DFE in relation to normal physiologic blood flow. With further investigations, estimating the time of final use of an inhalant prior to death may be deciphered from such patterns, although a degree of caution should be applied in deaths resulting from severe trauma in which normal tissue structure is compromised because postmortem redistribution may result.

Percutaneous absorption and distribution of methanol in a homicide.

A woman was alleged to have committed suicide by consuming a gasoline additive shortly before jumping from a second floor balcony within her home. She was found dead by police with a multitude of injuries, lying nude in a partially evaporated unknown residue that was later determined to be methanol. Samples collected at autopsy were found to contain methanol in the following concentrations: femoral blood 31.2 mg/dL, pulmonary artery blood 111.0 mg/dL, aortic blood 77.8 mg/dL, vitreous fluid 196.4 mg/dL, brain 22.0 mg/100 g, liver 21.2 mg/100 g, and kidney 25.9 mg/100 g using a headspace gas chromatographic method. Significantly, no methanol was detected in samples recovered from the esophagus, stomach, duodenum, small intestine, bile, or urine. These findings are inconsistent with either recent or delayed oral ingestion of methanol. We concluded that absorption of methanol occurred dermally and through the oral mucosa as she lay dying and saturated in the fuel additive. Based upon the toxicological data and a comprehensive forensic investigation (including documentation and analysis of evidence recovered at the scene and the autopsy), the cause of death was determined to be blunt impact trauma and methanol poisoning.

Hormone and Drug-Mediated Modulation of Glucose Metabolism in a Microscale Model of the Human Liver.

Due to its central role in glucose homeostasis, the liver is an important target for drug development efforts for type 2 diabetes mellitus (T2DM). Significant differences across species in liver metabolism necessitate supplementation of animal data with assays designed to assess human-relevant responses. However, isolated primary human hepatocytes (PHHs) display a rapid decline in phenotypic functions in conventional monolayer formats. Cocultivation of PHHs with specific stromal cells, especially in micropatterned configurations, can stabilize some liver functions for ~4 weeks in vitro. However, it remains unclear whether coculture approaches can stabilize glucose metabolism that can be modulated with hormones in PHHs. Thus, in this study, we compared commonly employed conventional culture formats and previously developed micropatterned cocultures (MPCCs) of cryopreserved PHHs and stromal fibroblasts for mRNA expression of key glucose metabolism genes (i.e., phosphoenolpyruvate carboxykinase-1 [PCK1]) and sensitivity of gluconeogenesis to prototypical hormones, insulin and glucagon. We found that only MPCCs displayed high expression of all transcripts tested for at least 2 weeks and robust gluconeogenesis with responsiveness to hormones for at least 3 weeks in vitro. Furthermore, MPCCs displayed glycogen storage and lysis, which could be modulated with hormones under the appropriate feeding and fasting states, respectively. Finally, we utilized MPCCs in proof-of-concept experiments where we tested gluconeogenesis inhibitors and evaluated the effects of stimulation with high levels of glucose as in T2DM. Gluconeogenesis in MPCCs was decreased after stimulation with drugs (i.e., metformin) and the PHHs accumulated significant amount of lipids following incubation with excess glucose (i.e., 340% in 50 mM glucose relative to physiologic 5 mM glucose controls). In conclusion, MPCCs provide a platform to study glucose metabolism and hormonal responsiveness in cryopreserved PHHs from multiple donors for several weeks in vitro. This model is also useful to study the effects of drugs and overnutrition for applications in T2DM.

Peer-led problem-based learning in interprofessional education of health professions students.

BACKGROUND: The role of peer teachers in interprofessional education has not been extensively studied. This study is designed to determine if peer-teacher-led problem-based seminars can influence medical and pharmacy students' perceptions of interprofessional education. METHODS: Undergraduate medical and pharmacy students participated in one-hour problem-based learning seminars held over the course of 16 weeks. A case-control study design was used to compare perceptions of interprofessional education between students who participated in seminars and students who did not participate in seminars. The validated Interdisciplinary Education Perception Scale (IEPS) was used to assess perceptions of interprofessional education and was distributed to medical and pharmacy students at the conclusion of 16 weeks of seminars. A two-tailed t-test was used to determine significance between groups. A survey was also distributed to all students regarding perceived barriers to involvement in interprofessional education training. RESULTS: In total, 97 students responded to IEPS (62 medical, 35 pharmacy). Data showed significantly higher perception of professional cooperation among medical students (p=0.006) and pharmacy students (p=0.02) who attended interprofessional seminars compared to those who did not attend. One hundred and nine students responded to the survey regarding perceived barriers to interprofessional education, with the two most common barriers being: 'I am not aware of interprofessional education opportunities' (61.5%) and 'I do not have time to participate' (52.3%). CONCLUSION: Based on this data we believe peer-teacher-led problem-based interprofessional seminars can be used to increase medical and pharmacy students' perceived need for professional cooperation. Currently, major barriers to interprofessional education involvement are awareness and time commitment. Undergraduate health professions education can incorporate student-led seminars to improve interprofessional education.