Intraneural Melanoma Identified With MART-1 Immunostaining in Mohs Micrographic Surgery.

Mohs micrographic surgery (MMS) utilizing melanoma antigen recognized by T-cells (MART-1) immunostaining is an increasingly common method of treatment for minimally invasive melanoma in anatomically constrained areas such as the face, ears, or acral sites. Neurotropic melanoma, also known as neurotrophism in melanoma, refers to the invasion of melanoma cells into the nerves. As such, these tumors can extend well beyond anticipated clinical tumor margins which can increase the risk of local recurrence. Here, we present a case of neurotropic melanoma successfully identified during MMS using MART-1 immunostaining, which was then confirmed with permanent sectioning.

Anti-CD20 monoclonal antibodies in multiple sclerosis: Rethinking the current treatment strategy.

Anti-CD20 monoclonal antibodies are highly-effective B-cell-depleting therapies in multiple sclerosis (MS). These treatments have expanded the arsenal of highly effective disease-modifying therapies, and have changed the landscape in understanding the pathophysiology of MS and the natural course of the disease. Nevertheless, these treatments come at the cost of immunosuppression and risk of serious infections, diminished vaccination response and treatment-related secondary hypogammaglobulinemia. However, the COVID pandemic has given way to a possibility of readapting these therapies, with most notably extended dosing intervals. While these new strategies show efficacy in maintaining inflammatory MS disease control, and although it is tempting to speculate that tailoring CD20 therapies will reduce the negative outcomes of long-term immunosuppression, it is unknown whether they provide meaningful benefit in reducing the risk of treatment-related secondary hypogammaglobulinemia and serious infections. This review highlights the available anti-CD20 therapies that are available for treating MS patients, and sheds light on encouraging data, which propose that tailoring anti-CD20 monoclonal antibodies is the next step in rethinking the current treatment strategy.

Tranexamic Acid Prevention of Hemorrhagic Complications Following Interpolated Flap Repair: A Single-Center, Retrospective, Cohort Study.

BACKGROUND: Tranexamic acid (TXA) is increasingly being used to prevent hemorrhagic complications after dermatologic surgery. Interpolated flap repairs following Mohs micrographic surgery are at risk for increased bleeding events and unplanned health care utilization, particularly among patients on antithrombotic medication. OBJECTIVE: To assess bleeding events after interpolated flap repair in patients receiving TXA compared with those who did not. MATERIALS AND METHODS: A retrospective review identified interpolated flap repairs in a 5-year period. Hemorrhagic complications were analyzed, defined as major bleeding events, which included all unplanned medical visits, and minor bleeding events, which included any unplanned patient phone calls or messages through electronic medical record. RESULTS: One hundred fifteen patients had interpolated flap repair during the 5-year period, of which 21 (18.3%) received TXA postprocedure. Twenty-seven bleeding events were identified in the non-TXA group compared with 1 event in the TXA-treated group. Patients who received TXA were less likely to have had a bleeding event (28.7% vs 4.8%, p < .01). CONCLUSION: Patients undergoing interpolation flap repair were less likely to experience a bleeding event after subcutaneous injection of TXA.

Bilateral Transposition Flaps With Split-Thickness Skin Grafting of Secondary Defects After a Large Mohs Micrographic Surgery Defect With Exposed Calvarium.

Large, full-thickness defects of the scalp create a common reconstructive dilemma following Mohs micrographic surgery. In cases with exposed calvarium, transposition flap(s) followed by split-thickness skin graft(s) to the secondary defect is an effective method of reconstruction that allows for same-day repair, full defect coverage, and good functional outcomes. Herein, we present the reconstruction of a large scalp defect utilizing bilateral transposition flaps followed by split-thickness skin grafts of the secondary defects.

Direct Determination of Fission-Barrier Heights Using Light-Ion Transfer in Inverse Kinematics.

We demonstrate a new technique for obtaining fission data for nuclei away from ß stability. These types of data are pertinent to the astrophysical r process, crucial to a complete understanding of the origin of the heavy elements, and for developing a predictive model of fission. These data are also important considerations for terrestrial applications related to power generation and safeguarding. Experimentally, such data are scarce due to the difficulties in producing the actinide targets of interest. The solenoidal-spectrometer technique, commonly used to study nucleon-transfer reactions in inverse kinematics, has been applied to the case of transfer-induced fission as a means to deduce the fission-barrier height, among other variables. The fission-barrier height of ^{239}U has been determined via the ^{238}U(d,pf) reaction in inverse kinematics, the results of which are consistent with existing neutron-induced fission data indicating the validity of the technique.

Permanent section margin concordance after Mohs micrographic surgery with immunohistochemistry for invasive melanoma and melanoma in situ: A retrospective dual-center analysis.

BACKGROUND: Mohs micrographic surgery (MMS) for melanoma practices vary among dermatologic surgeons. The implementation of immunohistochemical staining in MMS for melanoma mitigates challenges associated with slide interpretation; however, the reliability of melanoma antigen recognized by T cells 1 (MART-1), the preferred immunostain for melanoma, has yet to be compared with permanent section pathology. OBJECTIVE: To assess concordance rates of MART-1 frozen sections and permanent section pathologic interpretation of melanoma treated with MMS. METHODS: A dual-center retrospective analysis was conducted to collect concordance and demographic data. Chi-square tests were performed for group comparisons of categorical variables. RESULTS: Of the 379 permanent sections sent, 367 were concordant with frozen section pathology for an overall concordance rate of 96.8%. Cases were stratified into indeterminately concordant and indisputably concordant. Twenty-two (6%) of cases were indeterminately concordant, whereas 345 (94.0%) of cases were indisputably concordant. LIMITATIONS: The concordance rate is derived from a comparison of adjacent tissue margins, an inevitable consequence of utilizing 2 techniques. CONCLUSION: To the author's knowledge, this study represents the largest investigation examining concordance rates of MART-1 frozen sections in Mohs for melanoma. High concordance disputes the ongoing need for additional permanent margins when using MART-1 in routine cases.

Quenching of Single-Particle Strength in A=15 Nuclei.

Absolute cross sections for the addition of s- and d-wave neutrons to ^{14}C and ^{14}N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and proton separation energies, ΔS, is around -20 MeV for the ^{14}C+n system and +8 MeV for ^{14}N+n. The population of the 1s_{1/2} and 0d_{5/2} orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of ^{9}Be and ^{12}C. The simultaneous technique used removes many systematic uncertainties.

Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients: A Systematic Review of Tumor Profiling Studies.

As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.

Enamel Caries Detection and Diagnosis: An Analysis of Systematic Reviews.

Detection and diagnosis of caries-typically undertaken through a visual-tactile examination, often with supporting radiographic investigations-is commonly regarded as being broadly effective at detecting caries that has progressed into dentine and reached a threshold where restoration is necessary. With earlier detection comes an opportunity to stabilize disease or even remineralize the tooth surface, maximizing retention of tooth tissue and preventing a lifelong cycle of restoration. We undertook a formal comparative analysis of the diagnostic accuracy of different technologies to detect and inform the diagnosis of early caries using published Cochrane systematic reviews. Forming the basis of our comparative analysis were 5 Cochrane diagnostic test accuracy systematic reviews evaluating fluorescence, visual or visual-tactile classification systems, imaging, transillumination and optical coherence tomography, and electrical conductance or impedance technologies. Acceptable reference standards included histology, operative exploration, or enhanced visual assessment (with or without tooth separation) as appropriate. We conducted 2 analyses based on study design: a fully within-study, within-person analysis and a network meta-analysis based on direct and indirect comparisons. Nineteen studies provided data for the fully within-person analysis and 64 studies for the network meta-analysis. Of the 5 technologies evaluated, the greatest pairwise differences were observed in summary sensitivity points for imaging and all other technologies, but summary specificity points were broadly similar. For both analyses, the wide 95% prediction intervals indicated the uncertainty of future diagnostic accuracy across all technologies. The certainty of evidence was low, downgraded for study limitations, inconsistency, and indirectness. Summary estimates of diagnostic accuracy for most technologies indicate that the degree of certitude with which a decision is made regarding the presence or absence of disease may be enhanced with the use of such devices. However, given the broad prediction intervals, it is challenging to predict their accuracy in any future "real world" context.

Impact on patients of the coronovirus disease 2019 pandemic and postponement of cochlear implant surgery: a qualitative study.

OBJECTIVE: This study aimed to explore the impact of the coronavirus disease 2019 pandemic and postponement of elective surgical procedures for profoundly deaf patients awaiting cochlear implantation. METHOD: Open-ended questionnaires were sent to all adult patients awaiting cochlear implantation surgery. Qualitative analysis was performed using a grounded theory approach. RESULTS: Participants described a primarily negative impact on wellbeing from the surgery delay, expressing feelings of isolation or loneliness. Low mood, depression or hopelessness were commonly expressed by elderly participants; frustration and anxiety were described by young adults. Participants described a negative impact on their general daily life, describing difficulties communicating with facemasks and struggles with reliance on telephone communication because of social distancing. Despite these significant psychosocial challenges, only a minority described adaptive coping strategies. DISCUSSION: Profoundly deaf patients may be at greater psychosocial risk because of unique challenges from their hearing disability. Our findings can be used to develop evidence-driven strategies to improve communication, wellbeing and quality of life.

A case of idiopathic acquired leukonychia totalis in a 17-year-old boy.

Whitening of the nail, or leukonychia, can have a wide range of etiologies including genetic disorders, trauma, poisoning, autoimmune disorders, and infections. Here we detail a case of idiopathic acquired leukonychia totalis in a 17-year-old boy. This condition has been reported 13 times in the literature previously, with only young boys being affected. Proper diagnosis may help minimize unnecessary investigations and prevent additional psychological stress over whether an underlying disease is present.

The contribution of global aviation to anthropogenic climate forcing for 2000 to 2018.

Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr-1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr-1. Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m-2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m-2), CO2 (34.3 mW m-2), and NOx (17.5 mW m-2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m-2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.

Normal and abnormal response to sperm deposition in female dogs: A review and new hypotheses for endometritis.

In mammalian species there are significant physiological responses of the female reproductive tract to the deposition of sperm. These are particularly notable in species where sperm are deposited directly into the uterus, and function both to facilitate sperm transport to the sperm reservoir, and to eliminate introduced contaminants. In the bitch, sperm are deposited into the vagina and are rapidly transported through the open cervix. Sperm are then distributed around the uterus by uterine contractions such that transportation to the tip of the uterine horns occurs within 1 min of the start of mating. The main sperm reservoir appears to be the distal part of the utero-tubal junction which forms a pre-uterine tube reservoir. Sperm remain attached here by their heads to uterine epithelium and remain viable. In non-capacitating conditions sperm slowly detach from this site and this seems important to replenish the uterine tube reservoir, where sperm may re-attach to the epithelium. Post-ovulatory signals trigger capacitation changes and subsequent hyperactivated motility that is associated with detachment of sperm from both reservoirs; thus facilitating fertilization. After mating, a physiological post-mating uterine inflammatory response occurs, evidenced by an influx of polymorphonuclear neutrophils, increased uterine contractions, an increased uterine artery blood flow and a decrease of the resistance index indicating a short-duration vasodilation. Disturbance of this tightly regulated system has the potential to impact fertility by a failure of elimination of the introduced contaminants (such that a clinically-significant post-breeding endometritis ensues) but also by impairing sperm transport.

Oxytocin receptor binding in the titi monkey hippocampal formation is associated with parental status and partner affiliation.

Social cognition is facilitated by oxytocin receptors (OXTR) in the hippocampus, a brain region that changes dynamically with pregnancy, parturition, and parenting experience. We investigated the impact of parenthood on hippocampal OXTR in male and female titi monkeys, a pair-bonding primate species that exhibits biparental care of offspring. We hypothesized that in postmortem brain tissue, OXTR binding in the hippocampal formation would differ between parents and non-parents, and that OXTR density would correlate with frequencies of observed parenting and affiliative behaviors between partners. Subjects were 10 adult titi monkeys. OXTR binding in the hippocampus (CA1, CA2/3, CA4, dentate gyrus, subiculum) and presubiculum layers (PSB1, PSB3) was determined using receptor autoradiography. The average frequency of partner affiliation (Proximity, Contact, and Tail Twining) and infant carrying were determined from longitudinal observations (5-6 per day). Analyses showed that parents exhibited higher OXTR binding than non-parents in PSB1 (t(8) = - 2.33, p = 0.048), and that OXTR binding in the total presubiculm correlated negatively with Proximity (r = - 0.88) and Contact (r = - 0.91), but not Tail Twining or infant carrying. These results suggest that OXTR binding in the presubiculum supports pair bonding and parenting behavior, potentially by mediating changes in hippocampal plasticity.

Reducing achievement gaps in undergraduate general chemistry could lift underrepresented students into a "hyperpersistent zone".

Students from underrepresented groups start college with the same level of interest in STEM majors as their peers, but leave STEM at higher rates. We tested the hypothesis that low grades in general chemistry contribute to this "weeding," using records from 25,768 students. In the first course of a general chemistry series, grade gaps based on binary gender, race/ethnicity, socioeconomic status, and family education background ranged from 0.12 to 0.54 on a four-point scale. Gaps persisted when the analysis controlled for academic preparation, indicating that students from underrepresented groups underperformed relative to their capability. Underrepresented students were less likely than well-represented peers to persist in chemistry if they performed below a C-, but more likely to persist if they got a C or better. This "hyperpersistent zone" suggests that reducing achievement gaps could have a disproportionately large impact on efforts to achieve equity in STEM majors and professions.

Comorbidity burden on receipt of adjuvant immunotherapy and survival in patients with stage III melanoma: an analysis of the National Cancer Database.

BACKGROUND: Comorbidity burden is associated with development of cancer, stage at diagnosis, and treatment outcomes. We evaluated the association between comorbidity burden, receipt of adjuvant immunotherapy, and survival in patients with stage III melanoma. METHODS: Using the National Cancer Database, we identified 16,906 patients with stage III melanoma who underwent surgery of the primary site. Outcomes included receipt of adjuvant immunotherapy and overall survival; independent variables included Charlson/Deyo comorbidity index (CDI) and receipt of adjuvant immunotherapy. RESULTS: Patients with CDI scores of two or more averaged 30.0% and 30.9% lower adjusted odds of receiving adjuvant immunotherapy relative to patients with a CDI score of zero or one, respectively (P = 0.001 and 0.002, respectively). Longer survival was associated with lower CDI scores (all P < 0.001) and receipt of adjuvant immunotherapy (P < 0.001). Patients who received adjuvant immunotherapy averaged 16.0% lower adjusted risk of death compared to patients who did not (P < 0.001), which was constant within all CDI cohorts. Patients with a CDI score of two or more averaged 53.4% and 39.1% higher adjusted risk of death relative to patients with a CDI score of zero or one (both P < 0.001). CONCLUSION: Greater comorbidity burden was associated with lower receipt of adjuvant immunotherapy; however, adjuvant immunotherapy provided similar survival benefit for patients' irrespective comorbidity burden. Our findings suggest that patients with stage III melanoma who have a greater comorbidity burden may benefit from adjuvant immunotherapy but should not replace careful patient selection by the clinician.

Procalcitonin Perplexity - Prolonged Idiopathic Elevation in Pleomorphic Sarcoma: A Case Report and Review of the Literature.

Historically, elevations in procalcitonin (PCT) have been implicated in medullary thyroid cancer and neuroendocrine tumors. More recently, the trending of PCT has been suggested as a monitor of infection to assess the presence, clearance and eradication of infection, especially in cancer patients. Its increase serves as a marker of bacterial infections. During homeostasis it is produced by most tissues in the body at an extremely low level (<.01 ng/mL) and is often induced by bacterial endotoxins. In cancer patients additional factors influence these levels. Metastasis in particular is linked with relatively higher PCT levels. We present a case of an afebrile patient with undifferentiated pleomorphic sarcoma who underwent 25 cycles of radiation therapy and presented one month later with elevated procalcitonin, lactic acid, and leukocytosis. All infectious work up was negative. Findings were incidental after a hospital visit for dehydration. Leukocytosis and lactic acidosis resolved after four days into the hospitalization. Procalcitonin, however, remained elevated over four months in the range of 2-5 ng/mL. The patient has no findings of metastatic disease. To our knowledge, there has never been a report in the literature describing a prolonged elevation of procalcitonin in a patient with a non-metastatic sarcoma without any signs of infection or any other underlying cause. The elevation of PCT has been noted in patients who suffered burns, trauma, minor and major surgery, and cardiogenic shock in addition to infection. Increases have served as signs of worsening patient outcomes and elevated rate of complications. Trending PCT can help in appropriated antibiotic use as it has been shown to decrease antibiotic use by 2.4 days. PCT trends have been increasing in value making idiopathic elevations found in combination undifferentiated pleomorphic sarcoma an important addition to the literature.

Validation of the Manchester spoken language development scale (MSLDS).

Introduction: Standardized outcome measures are importantfor accurately monitoring the language development of pre-lingually deaf children receiving auditory implants. Current commonly used outcome measures are time-consuming,limiting the practicality of regular testing. To address these limitations, the Manchester Spoken Language Development Scale (MSLDS) was developed as a quick and easily applicable interim measurement. This is an 11-point scale designed to provide a streamlined overview of a child's expressive language development. This study describes the MSLDS, evaluates its ease of use and inter-rater reliability, and outlines its application in the paediatric auditory implant population. Methods: Sixteen speech therapists and teachers for the deaf reviewed videos of paediatric cochlear implant assessmentsand rehabilitation sessions at a UK auditory implant centre. Twenty-five videos from fourteen children were used in this validation study. Reviewers were asked to evaluate a child's language development using the MSLDS by assigning a score for each video and to evaluate the ease of use of the scale. Each video wasrated by three different reviewers. Results: MSLDS scores showed a high degree of consistency between raters for each child. 8/25 (32%) videos demonstrated perfect agreement on the MSLDS. In 15/25 (60%) videos, there was a one-point difference between MSLDS scores. The remaining 2/25 (8%) videos varied by 2 points. Statistical analysis demonstrated an intra-class correlation coefficient (ICC) of 0.987, indicating a high level of agreement between users of the scale. Qualitative feedback from the raters suggested further modifications which have been incorporated into the scale. Conclusion: The high inter-rater agreement reflects the potential for the MSLDS to be a reliable tool for monitoring language development in the paediatric auditory implant population.