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Programmed cell death-1 (PD-1) inhibitors represent an effective treatment option for advanced cutaneous squamous cell carcinoma (cSCC). However, solid organ transplant (SOT) recipients with cSCC have traditionally been excluded from clinical trials. To assess the safety and efficacy of PD-1 inhibitors for stage III-IV cSCC in SOT recipients. A systematic review was performed using the PubMed, EMBASE, and Scopus databases. We identified 21 articles describing 33 SOT recipients (26 kidney, four liver, two lung, and one heart) with stage III-IV cSCC treated with PD-1 inhibitors. Eleven patients (33.3%) experienced allograft rejection. Of the 25 cases with iRECIST scores, twelve patients (48.0%) had a complete response (CR), eight (32.0%) showed a partial response (PR), three (12.0%) progressive disease, and two (8.0%) stable disease (SD). Including patients without available iRECIST scores, 21 patients (63.6%) showed tumor response. Eleven patients died, with six (54.5%) due to tumor progression and one (9.1%) due to allograft rejection after foregoing dialysis. PD-1 inhibitors demonstrate efficacy for advanced cSCC and confer a risk of allograft rejection in SOT recipients, requiring careful assessment of risks and benefits. If anti-PD-1 therapy is pursued, use of mTOR inhibitors, prophylactic steroids, and donor-derived cell-free DNA monitoring may mitigate the risk of rejection. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a potentially curative treatment option for patients with refractory cutaneous T‐cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft‐versus‐lymphoma effect. However, allo‐HSCT is not always curative; relapse of CTCL occurs in about half of patients post‐transplant. Treatment of relapsed CTCL after allo‐HSCT is challenging because post‐transplant patients are at high risk of graft‐versus‐host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies. The benefit of each potential therapy must therefore be weighed against its risk of graft versus host disease (GVHD). In this article, we review the management of relapsed CTCL after allo‐HSCT. We begin with an exemplative patient whose relapsed Sezary syndrome was successfully treated without development of GVHD. We also report high‐throughput T‐cell receptor sequencing data obtained during the patient's disease relapse and remission. We then review general guidelines for management of relapsed CTCL and summarize all reported cases and outcomes of relapsed CTCL after transplant. We conclude by reviewing the current CTCL therapies and their risk of GVHD. [ABSTRACT FROM AUTHOR]

Conclusion Nonmelanoma skin cancers seem associated with increased subclinical tumor extension and higher rates of recurrence with standard excision in HIV, particularly with CD4 <200, supporting the use of MMS in this population. Nonmelanoma skin cancers (NMSCs), specifically basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are the most common malignancies worldwide. [Extracted from the article]

Https://doi.org/10.1093/ced/llac134 Dear Editor, We read with great interest the study in I Clinical and Experimental Dermatology i by Shah I et al i .[1] and commend them for providing an updated analysis of skin of colour (SoC) representation in dermatology educational resources. Top-down approach for increasing skin of colour representation in dermatology: emphasizing greater representation of skin of colour in national board examinations. Currently, the USMLEs overwhelmingly test dermatological conditions depicted in lighter skin types; in a recent study Meckley I et al i .[4] analysed self-assessments released by the National Board of Medical Examiners, the authors of the USMLEs, and found SoC representation to be a mere 24%. [Extracted from the article]

Dear Editor, Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common forms of cutaneous T-cell lymphoma (CTCL). Stimulating the Anti-Tumor Immune Response Bexarotene, psoralen plus ultraviolet A (PUVA), and extracorporeal photopheresis (ECP) are all agents that result in apoptosis of malignant cells. While there are increasing numbers of available therapies, CTCL remains incurable without allogeneic stem cell transplantation, and therefore treatment is primarily aimed at improving symptoms and maintaining responses. [Extracted from the article]

The transition from wakefulness to sleep is accompanied by widespread changes in brain functioning. Here we investigate the implications of this transition for interregional functional connectivity and their dynamic changes over time. Simultaneous EEG-fMRI was used to measure brain functional activity of 21 healthy participants as they transitioned from wakefulness into sleep. fMRI volumes were independent component analysis (ICA)-decomposed, yielding 42 neurophysiological sources. Static functional connectivity (FC) was estimated from independent component time courses. A sliding window method and k-means clustering (k = 7, L2-norm) were used to estimate dynamic FC. Static FC in Wake and Stage-2 Sleep (NREM2) were largely similar. By contrast, FC dynamics across wake and sleep differed, with transitions between FC states occurring more frequently during wakefulness than during NREM2. Evidence of slower FC dynamics during sleep is discussed in relation to sleep-related reductions in effective connectivity and synaptic strength. [ABSTRACT FROM AUTHOR]

Henoch Schönlein purpura (HSP), also known as IgA vasculitis, is a systemic small‐vessel vasculitis typically occurring in children 3–15 years of age, with peak incidence at 4–6 years. It is characterized by a constellation of symptoms including palpable purpura, arthralgias or arthritis, abdominal pain including intussusception, and renal involvement. We report a patient with these clinical findings whose IgA immunofluorescence was negative but with a presumptive diagnosis of HSP at 16 months of age, significantly younger than the classic population. This condition rarely affects this age group, and we highlight the importance of considering vasculitis in children of all ages, as a failure to diagnose could lead to insufficient long‐term monitoring, particularly regarding renal function. [ABSTRACT FROM AUTHOR]

Our patient represents the first reported case of neoadjuvant immune checkpoint inhibitor (ICI) therapy for stage II melanoma. At this time, surgical resection and adjuvant therapy remain the standard of care for high-risk stage II and clinical stage III melanoma.[1] However, appropriate patients can be considered for neoadjuvant therapy in ongoing clinical trials. [Extracted from the article]

Mogamulizumab is a novel monoclonal antibody designed to target CC chemokine receptor 4 (CCR4), which is expressed by tumor cells in cutaneous T-cell lymphoma (CTCL). In clinical trials, mogamulizumab monotherapy has demonstrated efficacy in reducing tumor burden in advanced CTCL, particularly in the peripheral blood. In clinical practice at our center, mogamulizumab has been combined with other agents such as systemic interferon, systemic retinoids, and extracorporeal photopheresis for an enhanced synergistic effect. There is limited published research on mogamulizumab combination therapy. This study evaluates the clinical efficacy of mogamulizumab in combination with systemic interferon, retinoids, and/or extracorporeal photopheresis for therapy of CTCL. Nineteen patients on this regimen at our academic center were identified. Treatment response rates, progression-free survival, duration of response, and adverse effects were characterized by retrospective chart review. All patients on this regimen at our center had an initial partial or complete response. Moreover, responses were durable, and the regimen was well-tolerated with few grade 3 adverse effects. These results demonstrate the utility of a multimodality approach to the therapy of CTCL with mogamulizumab and warrant further confirmation. [ABSTRACT FROM AUTHOR]

The pathogenesis of psoriasis may involve a breakdown of immune tolerance to cutaneous microorganisms. Psoriasis is associated with a higher incidence of Crohn disease and periodontitis, two diseases involving impaired tolerance and abnormal immune activation in response to intestinal and oral microbiota, respectively. In addition, guttate and chronic plaque psoriasis are associated with Streptococcus pyogenes colonization. The aim of this review is to characterize the microorganisms implicated in psoriasis by examining results of major association studies and possible mechanisms of pathogenesis. Although studies show relative increases in Streptococcus and Staphylococcus and decreases in Malassezia and Cutibacterium, they differ in methods of sampling and methods of microbial analysis. As such, no definitive associations between microbes and psoriasis have been found to date. It also remains unclear if changes in the microbiomal composition have a causal association with psoriasis or are simply a consequence of the inflammatory microenvironment. Techniques enabling strain-level analysis rather than species-level analysis of the skin microbiome are likely necessary to determine microbiomal signatures of psoriasis. Future investigations may lead to new diagnostic tests and novel treatments, such as probiotics or bacterial transplantation. [ABSTRACT FROM AUTHOR]

Folliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) with folliculotropic, atypical lymphocytes that may or may not have mucin deposition surrounding the hair follicle. Follicular mucinosis (FM) is a primary or secondary finding in FMF, lupus, or collagen vascular diseases that is only a histological process of mucin deposition surrounding the hair follicles. We present a case of a 6-year-old boy who had features of both FMF and primary follicular mucinosis (PFM). The case reveals key insights on FMF with concurrent FM in pediatric patients and how to differentiate between FMF and PFM. [ABSTRACT FROM AUTHOR]

Abstract: Mycosis fungoides with large‐cell transformation is historically associated with a poor prognosis. Pediatric cases of mycosis fungoides with large‐cell transformation are rare, with only three other cases reported in the literature. We present the first case of a child with almost complete remission of his mycosis fungoides with large‐cell transformation shortly after administration of psoralen plus ultraviolet A, interferon‐alfa, and localized radiation. [ABSTRACT FROM AUTHOR]

We present the extraordinary case of a 72-year-old man with a history of primary cutaneous peripheral T-cell lymphoma not otherwise specified (pcPTCL-NOS) previously controlled with topical agents who developed tumours in a sporotrichoid pattern. Culture of the tumours was negative, and histopathology showed findings consistent with recurrent pcPTCL. The tumours were successfully treated with localised radiation therapy. Sporotrichoid lesions are an extremely rare and atypical presentation of cutaneous lymphoma, with only 2 other cases reported in the literature. Our case reinforces the need to include cutaneous lymphoma in the differential diagnosis of nodules on the extremities spreading in a sporotrichoid pattern. Clinical recognition of this atypical presentation of cutaneous lymphoma allows for prompt, effective treatment, which might include localised radiation therapy. [ABSTRACT FROM AUTHOR]

Studies that explore associations between the local food environment and diet routinely use global regression models, which assume that relationships are invariant across space, yet such stationarity assumptions have been little tested. We used global and geographically weighted regression models to explore associations between the residential food environment and fruit and vegetable intake. Analyses were performed in 4 boroughs of London, United Kingdom, using data collected between April 2012 and July 2012 from 969 adults in the Olympic Regeneration in East London Study. Exposures were assessed both as absolute densities of healthy and unhealthy outlets, taken separately, and as a relative measure (proportion of total outlets classified as healthy). Overall, local models performed better than global models (lower Akaike information criterion). Locally estimated coefficients varied across space, regardless of the type of exposure measure, although changes of sign were observed only when absolute measures were used. Despite findings from global models showing significant associations between the relative measure and fruit and vegetable intake (β = 0.022; P < 0.01) only, geographically weighted regression models using absolute measures outperformed models using relative measures. This study suggests that greater attention should be given to nonstationary relationships between the food environment and diet. It further challenges the idea that a single measure of exposure, whether relative or absolute, can reflect the many ways the food environment may shape health behaviors. [ABSTRACT FROM AUTHOR]

Background context Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure for patients presenting with cervical radiculopathy, myelopathy, or deformity. A systematic literature review and meta-analysis of pseudoarthrosis rates associated with ACDF with plate fixation have not been previously performed. Purpose The purpose of this study was to identify all prospective studies reporting pseudoarthrosis rates for ACDF with plate fixation. Study design/setting This study is based on a systematic review and meta-analysis. Patient sample Studies reporting pseudoarthrosis rates in patients who received one-, two-, or three-level ACDF surgeries were included. Outcome measures Outcomes of interest included reported pseudoarthrosis events after ACDF with plate fixation. Methods We conducted a MEDLINE, SCOPUS, Web of Science, and EMBASE search for studies reporting complications for ACDF with plate fixation. We recorded pseudoarthrosis events from all included studies. A meta-analysis was performed to calculate effect summary mean values, 95% confidence intervals (CIs), Q statistics, and I 2 values. Forest plots were constructed for each analysis group. Results Of the 7,130 retrieved articles, 17 met the inclusion criteria. The overall pseudoarthrosis rate was 2.6% (95% CI: 1.3–3.9). Use of autograft fusion (0.9%, 95% CI: –0.4 to 2.1) resulted in a reduced pseudoarthrosis rate compared with allograft fusion procedures (4.8%, 95% CI: 1.7–7.9). Studies were separated based on the length of follow-up: 12 to 24 and greater than 24 months. These groups reported rates of 3.1% (95% CI: 1.2–5.0) and 2.3% (95% CI: 0.1–4.4), respectively. Studies performing single-level ACDF yielded a rate of 3.7% (95% CI: 1.6–5.7). Additionally, there was a large difference in the rate of pseudoarthrosis in randomized controlled trials (4.8%, 95% CI: 2.6–7.0) versus prospective cohort studies (0.2%, 95% CI: –0.1 to 0.5), indicating that the extent of follow-up criteria affects the rate of pseudoarthrosis. Conclusions This review represents a comprehensive estimation of the actual incidence of pseudoarthrosis across a heterogeneous group of surgeons, patients, and ACDF techniques. The definition of pseudoarthrosis varied significantly within the literature. To ensure its diagnosis and prevent sequelae, standardized criteria need to be established. This investigation sets the framework for surgeons to understand the impact of surgical techniques on the rate of pseudoarthrosis. [ABSTRACT FROM AUTHOR]

Objective: To demonstrate the clinical efficacy of topical 5% imiquimod for mycosis fungoides (MF) tumors. Background: Treatment of tumor-stage MF represents a therapeutic challenge because of a limited number of effective topical therapies. Single tumors can be treated with localized radiation but may recur. Systemic therapies are also an option but are associated with serious adverse effects. Imiquimod is a topical agent whose efficacy has been documented in treating MF patches and plaques as well as one case of tumor-stage disease. Methods: We present two stage IIB MF patients, including one with large cell transformation, whose tumors were treated with imiquimod 5% cream after failing prior therapies. Results: The MF tumors in both patients demonstrated a complete response to imiquimod 5% cream without recurrence over 8 years and 2 years of follow-up, respectively. One patient experienced application site irritation and flu-like symptoms as adverse effects. Conclusions: Our case series is only the second report in the literature demonstrating complete resolution of MF tumors with topical imiquimod. An additional therapeutic option for tumor-stage MF, imiquimod may represent an effective alternative to localized radiation for isolated MF tumors and warrants further investigation in the treatment of various stages of MF. [ABSTRACT FROM AUTHOR]

Organ transplant recipients receiving immunosuppression have an increased risk of developing post-transplant lymphoproliferative diseases (PTLDs). Traditionally, PTLDs refer to Epstein-Barr virus (EBV)-induced B-cell lymphoma. However, post-transplant T-cell lymphoma may also occur and tends to have a poorer response to reduced immunosuppressive therapy. As such, additional therapy is often needed for post-transplant T-cell lymphoma, including post-transplant cutaneous T-cell lymphoma (PT-CTCL). We present only the third case of PT-CTCL occurring after liver transplantation. The patient was diagnosed with stage IB mycosis fungoides (MF). His lesions were refractory to multiple skin-directed therapies, and so he was given oral bexarotene 150 mg daily and his oral tacrolimus dose was decreased to 2 mg daily. Remarkably, his MF patches have demonstrated a complete response to oral bexarotene 75 mg daily without recurrence over 11 years of follow-up. He developed hypertriglyceridemia with bexarotene 150 mg, so his dose was decreased to 75 mg, without loss of response. Our report is the second to describe PT-CTCL demonstrating a long-term complete response to oral bexarotene. Given its anti-carcinogenic properties and favorable toxicity profile, oral bexarotene represents an appealing treatment option for PT-CTCL refractory to skin-directed therapies. [ABSTRACT FROM AUTHOR]

Background: Populations living in urban areas experience greater health inequalities as well as higher absolute burdens of illness. It is well-established that a range of social and environmental factors determine these differences. Less is known about the relative importance of these factors in determining adolescent health within a super diverse urban context. Methods: A cross-sectional sample of 3,105 adolescent participants aged 11 to 12 were recruited from 25 schools in the London boroughs of Newham, Tower Hamlets, Hackney and Barking & Dagenham. Participants completed a pseudo-anonymised paper-based questionnaire incorporating: the Warwick-Edinburgh Mental Well-being Scale used for assessing positive mental well-being, the Short Moods and Feelings Questionnaire based on the DSM III-R criteria for assessment of depressive symptoms, the Youth-Physical Activity Questionnaire and a self-assessment of general health and longstanding illness. Prevalence estimates and unadjusted linear models estimate the extent to which positive well-being scores and time spent in physical/sedentary activity vary by socio-demographic and environmental indicators. Logistic regression estimated the unadjusted odds of having fair/(very)poor general health, a long standing illness, or depressive symptoms. Fully adjusted mixed effects models accounted for clustering within schools and for all socio-demographic and environmental indicators. Results: Compared to boys, girls had significantly lower mental well-being and higher rates of depressive symptoms, reported fewer hours physically active and more hours sedentary, and had poorer general health after full adjustment. Positive mental well-being was significantly and positively associated with family affluence but the overall relationship between mental health and socioeconomic factors was weak. Mental health advantage increased as positive perceptions of the neighbourhood safety, aesthetics, walkability and services increased. Prevalence of poor health varied by ethnic group, particularly for depressive symptoms, general health and longstanding illness suggesting differences in the distribution of the determinants of health across ethnic groups. Conclusions: During adolescence perceptions of the urban physical environment, along with the social and economic characteristics of their household, are important factors in explaining patterns of health inequality. [ABSTRACT FROM AUTHOR]

Study Design: Cost-effectiveness analysis with decision analysis and meta-analysis.Objective: To determine the relative cost-effectiveness of anterior cervical discectomy with fusion (with autograft, allograft, or spacers), anterior cervical discectomy without fusion (ACD), and cervical disc replacement (CDR) for the treatment of 1-level cervical disc disease.Summary Of Background Data: There is debate as to the optimal anterior surgical strategy to treat single-level cervical disc disease. Surgical strategies include 3 techniques of anterior cervical discectomy with fusion (autograft, allograft, or spacer-assisted fusion), ACD, and CDR. Several controlled trials have compared these treatments but have yielded mixed results. Decision analysis provides a structure for making a quantitative comparison of the costs and outcomes of each treatment.Methods: A literature search was performed and yielded 156 case series that fulfilled our search criteria describing nearly 17,000 cases. Data were abstracted from these publications and pooled meta-analytically to estimate the incidence of various outcomes, including index-level and adjacent-level reoperation. A decision analytic model calculated the expected costs in US dollars and outcomes in quality-adjusted life years for a typical adult patient with 1-level cervical radiculopathy subjected to each of the 5 approaches.Results: At 5 years postoperatively, patients who had undergone ACD alone had significantly (P < 0.001) more quality-adjusted life years (4.885 ± 0.041) than those receiving other treatments. Patients with ACD also exhibited highly significant (P < 0.001) differences in costs, incurring the lowest societal costs ($16,558 ± $539). Follow-up data were inadequate for comparison beyond 5 years.Conclusion: The results of our decision analytic model indicate advantages for ACD, both in effectiveness and costs, over other strategies. Thus, ACD is a cost-effective alternative to anterior cervical discectomy with fusion and CDR in patients with single-level cervical disc disease. Definitive conclusions about degenerative changes after ACD and adjacent-level disease after CDR await longer follow-up.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Study Design. Cost-effectiveness analysis with decision analysis and meta-analysis. Objective. To determine the relative cost-effectiveness of anterior cervical discectomy with fusion (with autograft, allograft, or spacers), anterior cervical discectomy without fusion (ACD), and cervical disc replacement (CDR) for the treatment of 1 -level cervical disc disease. Summary of Background Data. There is debate as to the optimal anterior surgical strategy to treat single-level cervical disc disease. Surgical strategies include 3 techniques of anterior cervical discectomy with fusion (autograft, allograft, or spacer-assisted fusion), ACD, and CDR. Several controlled trials have compared these treatments but have yielded mixed results. Decision analysis provides a structure for making a quantitative comparison of the costs and outcomes of each treatment. Methods. A literature search was performed and yielded 156 case series that fulfilled our search criteria describing nearly 17,000 cases. Data were abstracted from these publications and pooled meta-analytically to estimate the incidence of various outcomes, including index-level and adjacent-level reoperation. A decision analytic model calculated the expected costs in US dollars and outcomes in quality-adjusted life years for a typical adult patient with 1-level cervical radiculopathy subjected to each of the 5 approaches. Results. At 5 years postoperatively, patients who had undergone ACD alone had significantly (P < 0.001) more quality-adjusted life years (4.885 ± 0.041) than those receiving other treatments. Patients with ACD also exhibited highly significant (P < 0.001) differences in costs, incurring the lowest societal costs ($16,558 ± $539). Follow-up data were inadequate for comparison beyond 5 years. Conclusion. The results of our decision analytic model indicate advantages for ACD, both in effectiveness and costs, over other strategies. Thus, ACD is a cost-effective alternative to anterior cervical discectomy with fusion and CDR in patients with single-level cervical disc disease. Definitive conclusions about degenerative changes after ACD and adjacent-level disease after CDR await longer follow-up. [ABSTRACT FROM AUTHOR]

Dear Editor, First introduced by William H. Goeckerman in 1925, phototherapy has experienced a number of advancements over the years, including the development of modalities such as psoralen plus ultraviolet A (PUVA), narrowband ultraviolet B (NB-UVB), and photodynamic therapy. Most commonly used for psoriasis, phototherapy also represents an effective, low-cost therapeutic option for atopic dermatitis, vitiligo, mycosis fungoides (MF)/Sézary syndrome (SS), granuloma annulare, and acute and chronic graft-vs-host disease. Approaches to maintain the availability of UVA should be centered on exploring expanded uses of UVA through further clinical study and integrating dedicated phototherapy training for dermatology residents and fellows. [Extracted from the article]

Patient adherence to medications for common skin conditions has been extensively studied over the past two decades, and suboptimal adherence is a primary contributor to treatment failure. The impact of sub-par adherence in cutaneous T-cell lymphoma (CTCL) patients has been largely unexplored, and promoting adherence in this patient population may represent a promising area of consideration for improving treatment outcomes. We apply patient adherence strategies that have been studied in dermatology to CTCL and provide concrete examples of how these strategies can be used to improve adherence in the CTCL setting. Through the implementation of small changes in how we present and counsel about therapeutic options to our patients, we can maximize patient adherence, which has the potential to optimize therapy regimens and reduce treatment failure. [ABSTRACT FROM AUTHOR]

Between 2005 and 2007 there were 9071 traffic accidents involving bicycles within London and this paper demonstrates the utility of Geographic Information Systems as a tool for analysing and visualising these occurrences. Through linkage of these spatial locations to a street network dataset it was possible to create a variety of intelligence about the types of street infrastructure where accidents predominantly occur. Additionally, a network routing algorithm was adapted to account for the frequency of accidents within a series of proposed journeys. This pilot routing application compared the quickest route with an accident avoidance weighted route between a series of origins and destinations. The results demonstrated that the routes avoiding areas of high accident volume did not increase journey length significantly; however they did provide a "safer" route based on empirical evidence over the volume of accident locations. [ABSTRACT FROM AUTHOR]

The role of the cutaneous microbiome has been studied extensively in recent years, as dysbiosis is implicated in dermatologic disorders such as atopic dermatitis, psoriasis, hidradenitis suppurativa, seborrheic dermatitis, and rosacea, among others. Although the immunopathogenesis of MF and its leukemic variant Sezary syndrome (SS) remains largely unknown, chronic antigenic exposure has long been postulated to play a role.[1] If so, genetically susceptible individuals may be exposed to environmental and endogenous antigens, which may trigger the emergence of or perpetuate existing disease. Association of erythrodermic cutaneous T-cell lymphoma, superantigen-positive Staphylococcus aureus, and oligoclonal T-cell receptor V beta gene expansion. [Extracted from the article]

Examines the diffusion measurements of radioactive [sup 110m]Ag tracer in polycrystalline. Effects of silver doping on lead-containing ceramics; Importance of grain diffusion process on energy activation; Changes in grain size on different silver-doping levels.

Abstract: Atopic dermatitis is responsive to midpotency topical corticosteroids, which are the mainstay of treatment, yet many patients have disease that is “resistant” to triamcinolone prescribed for outpatient use. Such resistance is often due to poor adherence, but patients and caregivers may remain adamant that the steroid was ineffective and assure the physician that it was applied as recommended. We describe the case of a young girl with a 2‐year history of atopic dermatitis resistant to triamcinolone whose condition rapidly improved with continued use of triamcinolone. Our case raises the ethical dilemma of whether physicians should base treatment plans on what patients report or what evidence on adherence suggests. [ABSTRACT FROM AUTHOR]

Introduction: Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings.Areas Covered: Real-world studies on avelumab for MCC from North and South America, Europe, and Asia have been presented in this review. Most studies are on patients over age 70 and have a male-predominant sex ratio. Overall response rates range from 29.1% to 72.1%, (disease control rate: 60.0– 72.7%; complete response rate: 15.8%– 37.2%; partial rate: 18.2– 42.1%; stable disease: 7.1– 30.9%; progressive disease: 7.1– 40.0%) and median progression free survival ranges from 8.1 to 24.1 months depending on the population studied. Immunosuppressed patients appear to benefit from avelumab as well, with response rates equivalent to the general population. Patients receiving avelumab as a first-line agent tend to have better outcomes than those using it as a second-line therapy. Fatigue, infusion-related reactions, and dyspnea were some of the most common adverse events identified in real-world studies. Autoimmune hepatitis and thyroiditis were also observed.Conclusion: The use of avelumab as a safe and effective treatment option for advanced MCC is supported by real-world data, although additional study is required to assess long-term efficacy and safety outcomes. [ABSTRACT FROM AUTHOR]

Extracorporeal photopheresis (ECP) has been used for nearly 30 years in the treatment of cutaneous T-cell lymphoma. However, current clinical practice largely reserves ECP for patients with late-stage mycosis fungoides (MF) or Sézary syndrome or for those who are refractory to other therapies. We briefly describe a 48-year-old male who experienced long-term complete remission of his patch MF disease with ECP, and we suggest a role for ECP in the treatment of early-stage MF given evidence of its efficacy, safety, and tolerability. [ABSTRACT FROM AUTHOR]

Background: Mastocytosis describes a heterogeneous group of disorders arising from a clonal proliferation of mast cells. Given the lack of curative treatments for the cutaneous form, there is a significant need for superior therapies. Omalizumab is a recombinant DNA‐derived humanized IgG monoclonal antibody that selectively binds to human immunoglobulin E (IgE). It represents a potential treatment for the management of cutaneous mastocytosis, which currently has no standard treatment. Methods: Two patients were treated with subcutaneous omalizumab 300 mg every 4 weeks. Discussion: Patient 1 experienced 50% reduction in cutaneous infiltration and moderate improvement in pruritus. Patient 2 underwent 90% complete clearance of cutaneous lesions and reported full resolution of pruritus. The median duration of treatment was 24 weeks and time to response was 8 weeks. No significant changes in tryptase levels were observed. Both patients experienced injection site reactions. Conclusion: We provide evidence from two cases supporting the efficacy of IgE‐mediated therapy in the treatment of cutaneous mastocytosis. Even at a higher‐than‐standard dose (300 mg vs. 150 mg), the drug was well‐tolerated. As we await the results of pivotal clinical trials, omalizumab appears to be a promising treatment option in patients with cutaneous mastocytosis unresponsive to traditional therapies. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that causes disseminated eruptions of hypo‐ or hyperpigmented macules and wart‐like papules that can coalesce and scale. It is uniquely characterized by an increased susceptibility to specific human papillomavirus (HPV) genotypes. Classically, EV is associated with mutations of the EVER1/TMC6 and EVER2/TMC8 genes. The term “acquired” epidermodysplasia verruciformis was coined to describe an EV‐like syndrome that can develop in patients with a compromised immune system. Recent discoveries of other genes implicated in EV, including RHOH, MST‐1, and CORO1A, have complicated the classification of EV and EV‐like syndromes. Methods: We review the available data on epidermodysplasia verruciformis in the literature in order to propose a new classification system to encompass current and future developments on EV and EV‐like syndromes. Results: We propose classifying EV into: (1) classic genetic EV, (2) non‐classic genetic EV, and (3) acquired EV. Conclusion: The proposed categorization scheme provides a simple and logical way to organize the different cases of EV that have been described in the literature. This system organizes EV by its cause, allowing for a better understanding of the disease and helps differentiate EV from other causes of generalized verrucosis. [ABSTRACT FROM AUTHOR]

Trends over time in Pap and Pap-HPV cotesting for cervical cancer screening. Dear Editor, Melanoma is a melanocyte-derived malignant neoplasm that can develop on the skin or mucosa. Pap smear usage not only aids in the detection of genital melanomas but also at the population level is strongly associated with detection at a lower Breslow depth, the most important predictor of survival.4 In addition to screening for squamous intraepithelial lesions, the Pap smear can also yield an incidental diagnosis of cervical melanoma via cytology, of which several cases have been documented.5 Although the introduction of Pap-HPV cotesting has enhanced cervical cancer screening, it has also inadvertently compromised melanoma detection. [Extracted from the article]

Muir-Torre syndrome (MTS) is an autosomal dominant cancer syndrome that is a phenotypic variant of hereditary nonpolyposis colorectal carcinoma (HNPCC), or Lynch syndrome. Arch Dermatol Res. 2021; 313: 391 - 430. doi: 10.1007/s00403-020-02152-4 3 Graefe T, Wollina U, Schulz H, Burgdorf W. Muir-Torre syndrome - treatment with isotretinoin and interferon alpha-2a can prevent tumour development. Importantly, though, isotretinoin has shown efficacy in the treatment of sebaceous neoplasms associated with MTS, in addition to its well-documented effect on preventing KAs.2 Herein, we review the literature on the use of isotretinoin in MTS and suggest that isotretinoin chemoprophylaxis may represent a novel therapeutic paradigm in MTS. [Extracted from the article]

Abstract: Earth's inner core exhibits elastic anisotropy, but the cause of the texturing is uncertain: solidification, deformation, or some combination. In experiments presented here we deformed in torsion directionally solidified Zn‐3 wt pct Sn alloys at 0.97 of the melting temperature of pure Zn. We used a Zn‐rich alloy because Zn is hexagonal close‐packed at atmospheric pressure, as is likely Fe under inner core conditions. The directionally solidified alloys have the textured, columnar dendritic microstructure that has been proposed for the inner core. As a control we deformed in torsion the same alloy at the same temperature, but with a starting microstructure that is comparatively fine‐grained, equiaxed, and untextured. We find evidence that the directionally solidified alloys deform by means of grain boundary sliding, presumably accompanied by diffusion near the ends of the columnar crystals in order to preserve macroscopic shape. We also find that the directionally solidified alloys require approximately 3 times the torque to deform to the same strain than do the untextured alloys. Grain boundary sliding and greater hardness are due to insufficient slip systems to accommodate the strain, as a result of the texturing. This is supported by microcracking in the deformed directionally solidified alloys. Although the inner core is unlikely to exhibit semibrittle deformation, the experiments suggest that a directionally solidified inner core could have a higher viscosity than one with a finer‐grained, untextured microstructure and that grain boundary sliding may be a dominant deformation mechanism, in spite of the large grain size. [ABSTRACT FROM AUTHOR]

Extracutaneous involvement in mycosis fungoides (MF) carries a poor prognosis. Oral and gastrointestinal (GI) tract lesions are both rare locations of disease. We describe the clinical findings of one case with oral and GI MF complicated by perforation after systemic antineoplastic treatment, and review the relevant literature. The patient had a 1-year history of MF before development of tongue and palate tumors. He was treated with local electron beam radiation, but re-presented to the hospital after what was found to be small intestine perforation following systemic antineoplastic therapy. The case reveals key insights into the progression and complications of lymphomas with GI tract involvement. [ABSTRACT FROM AUTHOR]

Abstract: Numerous clinicopathological variants of mycosis fungoides have been described in the literature. Dermatomal or zosteriform mycosis fungoides is one reported variant but a clear aetiology has never been documented. We report a case of mycosis fungoides proved by biopsy and immunohistochemistry that developed in a 55‐year‐old man at the site of previous herpes zoster eruption. We also present a review of the relevant literature to add to the understanding of rare variants of mycosis fungoides and aid in the clinical recognition of zosteriform mycosis fungoides. [ABSTRACT FROM AUTHOR]

Despite the relationship between molecular structure and the occurrence of the twist-bend nematic phase being partially understood, very little is known about how these relationships are manifested for ether-linked bimesogens. In this article, we report several novel ether-linked bimesogens that exhibit the NTBphase and explore how the thermal properties of these materials are largely governed by the angle between the two aromatic, carbocyclic or rigid cyclic units. [ABSTRACT FROM AUTHOR]

Objective To develop a decision analytic model to calculate outcomes after treatment of cerebral aneurysms in elderly patients. Neurosurgical clipping and endovascular coiling for both ruptured and unruptured aneurysms were compared with predicted health-related quality of life (HRQoL) after treatment. Methods A Medline search of articles published in English between 1995 and June 2012 was performed using key words: ‘intracranial aneurysms', ‘treatment', or various combinations of ‘elderly', ‘older', or ‘decade’. Reports that met inclusion criteria used either the Glasgow Outcome Score or the modified Rankin Scale for outcomes, age >69, and intracranial aneurysm that was treated by endovascular coiling or surgical clipping. Data were collected by performing a comprehensive review of published reports. Meta-analysis (inverse variance-weighted, random effects) was used to calculate pooled values for probabilities and HRQoL. Results HRQoL was significantly higher for patients with coiled rather than clipped aneurysms in both ruptured ( p<0.01) and unruptured (p<0.01) aneurysm groups. Periprocedural mortality rates were significantly lower among patients with a coiled, unruptured aneurysm than among patients with a clipped, unruptured aneurysm (p=0.032). Sensitivity analysis and Monte Carlo simulation for both ruptured and unruptured aneurysms showed that overall HRQoL was significantly higher in coiled than in clipped patients. Conclusions As life expectancy increases, treatment of cerebral aneurysms in the elderly becomes more important. Given the results of this decision analysis and the continuous refinement in endovascular technology, embolization should strongly be considered as a first-line treatment for cerebral aneurysms in the elderly. [ABSTRACT FROM AUTHOR]

The viscosity of Earth's inner core (IC) plays a key role in its dynamics, being important for understanding IC convection, translation, super-rotation, and development of elastic anisotropy. However, estimates for the viscosity of the IC range from 1013 Pa⋅s to 1021 Pa⋅s. One difficulty in estimating the viscosity is that it is not simply a material property, but it depends on the rheology, i.e., the deformation mechanism, which in turns depends on factors such as the temperature, stress, grain size, and microstructure. To examine the effects of microstructure we have carried out constant strain rate torsional deformation experiments on directionally solidified hexagonal close packed (hcp) Zn-rich Sn alloys at high homologous temperature and atmospheric pressure. The directionally solidified hcp Zn-rich Sn alloys have a microstructure that consists of large, columnar, textured crystals composed of dendrites. This microstructure has been proposed for the IC, and hcp Zn at atmospheric pressure serves as an analog for hcp iron under IC conditions, including a likely basal slip (0001) <12'10>, along with some prismatic slip (101'0) <12'10> associated with twinning. The measured torque (or stress, which is a function of the geometry and deformation mechanism, which in turn depends on the grain size) continues to increase past what one would expect for steady state deformation, indicative of hardening. We are yet unclear as to the origin of the hardening, but our hypothesis is that it may involve the relatively few slip systems available in hcp systems, and the large, textured grains of directionally solidified alloys, so that not all strains are easily accommodated by the available slip systems. The semi-brittle behavior of the alloy also supports this hypothesis. An inner core with a textured, columnar microstructure might therefore be harder than estimates of its shear strength might predict. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examine experimentally annealing of directionally solidified Zn-rich Al. [•] Unlike in Zn-rich Sn, we do not find recrystallization and loss of texture. [•] However, new experiments on Zn-rich Sn also do not find recrystallization. [•] Relevant to textural changes of Earth’s inner core. [ABSTRACT FROM AUTHOR]

The vaccinated mice demonstrated significant tumor regression, and with a 79%-96% prevalence of CMS5-VP1 tumors in humans, VP1 may be an effective target for MCC vaccines. Hernandez et al.1 provide a detailed review on Merkel cell carcinoma (MCC), describing the pathologic role of the Merkel cell polyomavirus (MCPyV) while also discussing that MCC is an inherently immune-sensitive cancer. Unlike human papillomavirus vaccination guidelines, universal vaccine recommendations for MCC are impractical given the rarity of MCC.3 Nevertheless, as MCC recurrence has been noted to be between 25% and 75%, depending on stage,6 MCC vaccination still represents a valuable potential approach to reduce the mortality associated with MCC. [Extracted from the article]

Abstract: Mesophase pitch was investigated as a melt processable precursor to a compression or injection moldable all carbon bipolar plate. After shaping, carbonization to 1000°C or greater is required to achieve the desired electrical and mechanical properties, but gases evolved during this step lead to swelling. Carbon nanofiber was added to suppress swelling during carbonization and bypass the typical oxidation steps used when processing mesophase pitch. The addition of carbon nanofiber decreased swelling by increasing the viscosity of the melt. Carbonized materials with carbon nanofibers can show strengths (30–50MPa) and conductivities (20–80Scm−1) consistent with composite bipolar plate materials. The materials show conductivities below Department of Energy target values at the current carbonization temperatures, which were limited to 1000°C. The use of glass fibers as a secondary filler led to reduced gas permeability in porous samples. [ABSTRACT FROM AUTHOR]

• This was a large-scale empirical investigation of the impact of multilingualism on children's cognitive functioning. • The study utilized large samples, appropriate cognitive outcome measures, and multiple classifications of bilingualism. • There was no evidence of a "bilingual advantage" when confounding variables were controlled for using matched samples. • Bayesian analyses provided support for the null hypothesis that language status did not impact attentional disengagement. According to recent accounts, bilingualism in childhood confers an advantage in a specific domain of executive functioning termed attentional disengagement. The current study tested this hypothesis in 492 children (245 boys; M age = 10.98 years) from Canada, China, and Lebanon by testing for an association between language status and measures of attentional disengagement. Across the entire sample, monolinguals responded more quickly and accurately than bilinguals on a measure of attentional disengagement but differed in age, socioeconomic status, and general cognitive ability. Differences between monolinguals and bilinguals disappeared when the influence of these confounding variables was controlled using a matched samples analysis (n s = 105). Bayesian analyses further confirmed that the evidence was more likely under the null hypothesis than under the alternative hypothesis. In sum, there was little evidence of an association between language status and attentional disengagement in children. [ABSTRACT FROM AUTHOR]

Primary cutaneous CD4+ small‐ to medium‐sized pleomorphic T‐cell lymphoproliferative disorder (PCSM‐LPD) is a rare and low‐grade form of cutaneous T‐cell proliferation with the average age of diagnosis of 54 years. Because of its rarity, the etiology or exact clinicopathology of PCSM‐LPD remains unclear, with < 10 pediatric cases reported. A 13‐year‐old boy presented to our clinic with a raised tumor with PCSM‐LPD histology and was successfully treated with ultra‐low‐dose radiation therapy. While no standard of care has been established for pediatric PCSM‐LPD, this report represents an example of achieving remission in a pediatric tumor with minimal potential for therapy‐related long‐term toxicity. [ABSTRACT FROM AUTHOR]

Oral involvement in mycosis fungoides is unusual and portends a poor prognosis. The clinical findings of three new cases are described along with a differential diagnosis and review of the literature. For brevity, only one patient is discussed in detail below whereas the other two cases are solely described in table form. The patient had a four-year history of mycosis fungoides before developing an exophytic tongue tumor. He was treated with local electron beam radiation and is disease-free to date while being on maintenance therapy with oral bexarotene. Analysis of the data collected from our review of the literature and the present cases reveal key insights. [ABSTRACT FROM AUTHOR]

Background: Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. Methods: AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (µm²) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocytederived macrophages and rat AM was assessed in vitro by image analysis. Results: AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10-6 M, but not PGD2 10-6 M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10-6 M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). Conclusions: Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma. [ABSTRACT FROM AUTHOR]

Abstract: Space-filling polyhedral networks are commonly studied in biological, physical, and mathematical disciplines. The constraints governing the construction of each network varies considerably under each context, affecting the topological properties of the constituents. A method for mapping the topological symmetry of a space-filling population of polyhedra is presented, relative to all possible polyhedra. This method is applied to the topological comparison of populations generated by seven different processes: (i) natural grain growth in polycrystalline metal, ideal grain growth simulated by (ii) interface-tracking and (iii) phase-field methods, (iv) Poisson–Voronoi and (v) ellipsoid tessellations, and (vi) graph-theoretic and (vii) Monte Carlo enumerations of individual polyhedra. Evidence for topological bias in these populations is discussed. [Copyright &y& Elsevier]