Targeting Dysregulated Ion Channels in Liver Tumors with Venom Peptides.

The regulation of cellular processes by ion channels has become central to the study of cancer mechanisms. Designing molecules that can modify ion channels specific to tumor cells is a promising area of targeted drug delivery and therapy. Despite their potential in drug discovery, venom peptides-a group of natural products-have largely remained understudied and under-characterized. In general, venom peptides display high specificity and selectivity for their target ion channels. Therefore, they may represent an effective strategy for selectively targeting the dysregulation of ion channels in tumor cells. This review examines existing venom peptide therapies for different cancer types and focuses on the application of snail venom peptides in hepatocellular carcinoma (HCC), the most common form of primary liver cancer worldwide. We provide insights into the mode of action of venom peptides that have been shown to target tumors. We also explore the benefit of using new computational methods like de novo protein structure prediction to screen venom peptides and identify potential druggable candidates. Finally, we summarize the role of cell culture, animal, and organoid models in developing effective therapies against HCC and highlight the need for creating models that represent the most disproportionately affected ethnicities in HCC.

Primary Cutaneous Epithelioid Mesenchymal Tumor With a Novel ATP2B4::GLI1 Gene Fusion.

ABSTRACT: GLI1 gene alterations (rearrangement or amplification) have been found in several bone and soft tissue tumors including pericytic tumors, gastric plexiform fibromyxoma, gastroblastoma, and a various group of epithelioid tumors with regional recurrence or distant metastasis. In this article, we describe a case of primary cutaneous epithelioid mesenchymal tumor harboring hitherto not reported ATP2B4::GLI1 gene fusion. A 42-year-old man presented with a growing firm lesion on the left postauricular scalp. Microscopically, the shave biopsy specimen revealed a dermal-based nodular proliferation of relatively monotonous epithelioid cells with round to ovoid nuclei and pale eosinophilic cytoplasm, accompanied by prominent stromal vasculature. Significant cytologic atypia, necrosis, and mitotic activity were absent. The tumor cells were partially positive for CD34 and S-100 protein, but were negative for other markers, including SOX-10, keratins, and myogenic markers. An ATP2B4::GLI1 gene fusion was identified by next-generation sequencing. Array CGH was also performed, but it did not show relevant chromosomal copy number changes. Awareness of this rare cutaneous tumor, and thus, reporting of additional cases is necessary for further delineating its full clinicopathologic spectrum.

COVID-19 and celiac disease: a review.

The aim of this review is to broadly cover how the COVID-19 pandemic has affected individuals with celiac disease, including perceived risk, risk of contraction or severe infection, considerations regarding vaccination, access to gluten-free food during the pandemic, and possible long-term changes to the practice of celiac disease management spurred by the pandemic. While initially there was increased perceived risk about COVID-19 in the celiac disease population, studies have found that individuals with celiac disease are not at an increased risk of contracting or having a severe course compared to the general population. There is not yet evidence that COVID-19 infection will lead to an increase in celiac disease incidence, though more research on this topic with longer-term follow-up is necessary to make this determination. Limited access to in-person visits led to an increase in telemedicine, which was adopted swiftly by this patient population and may offer improved access in the long term. In summary, individuals with celiac disease do not appear to be at an increased risk of contracting COVID-19 or having a more severe disease course.

Continuous Long-Term Physical Activity Monitoring in Hemodialysis Patients.

Background: Physical inactivity is common in patients receiving hemodialysis, but activity patterns throughout the day and in relation to dialysis are largely unknown. This knowledge gap can be addressed by long-term continuous activity monitoring, but this has not been attempted and may not be acceptable to patients receiving dialysis. Methods: Ambulatory patients with end-stage kidney disease receiving thrice-weekly hemodialysis wore commercially available wrist-worn activity monitors for 6 months. Step counts were collected every 15 minutes and were linked to dialysis treatments. Physical function was assessed using the Short Physical Performance Battery (SPPB). Fast time to recovery from dialysis was defined as ≤2 hours. Mixed effects models were created to estimate step counts over time. Results: Of 52 patients enrolled, 48 were included in the final cohort. The mean age was 60 years, and 75% were Black or Hispanic. Comorbidity burden was high, 38% were transported to and from dialysis by paratransit, and 79% had SPPB <10. Median accelerometer use (199 days) and adherence (95%) were high. Forty-two patients (of 43 responders) reported wearing the accelerometer every day, and few barriers to adherence were noted. Step counts were lower on dialysis days (3991 [95% CI, 3187 to 4796] versus 4561 [95% CI, 3757 to 5365]), but step-count intensity was significantly higher during the hour immediately after dialysis than during the corresponding time on nondialysis days (188 steps per hour increase [95% CI, 171 to 205]); these levels were the highest noted at any time. Postdialysis increases were more pronounced among patients with fast recovery time (225 [95% CI, 203 to 248] versus 134 [95% CI, 107 to 161] steps per hour) or those with SPPB ≥7. Estimates were unchanged after adjustment for demographics, diabetes status, and ultrafiltration rate. Conclusions: Long-term continuous monitoring of physical activity is feasible in patients receiving hemodialysis. Highly granular data collection and analysis yielded new insights into patterns of activity after dialysis treatments.

Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Assessing coronavirus disease 2019 (COVID-19) transmission to healthcare personnel: The global ACT-HCP case-control study.

OBJECTIVE: To characterize associations between exposures within and outside the medical workplace with healthcare personnel (HCP) SARS-CoV-2 infection, including the effect of various forms of respiratory protection. DESIGN: Case-control study. SETTING: We collected data from international participants via an online survey. PARTICIPANTS: In total, 1,130 HCP (244 cases with laboratory-confirmed COVID-19, and 886 controls healthy throughout the pandemic) from 67 countries not meeting prespecified exclusion (ie, healthy but not working, missing workplace exposure data, COVID symptoms without lab confirmation) were included in this study. METHODS: Respondents were queried regarding workplace exposures, respiratory protection, and extra-occupational activities. Odds ratios for HCP infection were calculated using multivariable logistic regression and sensitivity analyses controlling for confounders and known biases. RESULTS: HCP infection was associated with non-aerosol-generating contact with COVID-19 patients (adjusted OR, 1.4; 95% CI, 1.04-1.9; P = .03) and extra-occupational exposures including gatherings of ≥10 people, patronizing restaurants or bars, and public transportation (adjusted OR range, 3.1-16.2). Respirator use during aerosol-generating procedures (AGPs) was associated with lower odds of HCP infection (adjusted OR, 0.4; 95% CI, 0.2-0.8, P = .005), as was exposure to intensive care and dedicated COVID units, negative pressure rooms, and personal protective equipment (PPE) observers (adjusted OR range, 0.4-0.7). CONCLUSIONS: COVID-19 transmission to HCP was associated with medical exposures currently considered lower-risk and multiple extra-occupational exposures, and exposures associated with proper use of appropriate PPE were protective. Closer scrutiny of infection control measures surrounding healthcare activities and medical settings considered lower risk, and continued awareness of the risks of public congregation, may reduce the incidence of HCP infection.

Vitiligo and Melanoma-Associated Vitiligo: Understanding Their Similarities and Differences.

BACKGROUND: There has been a significant increase in the number and efficacy of therapies for advanced melanoma. Immunotherapies, such as anti-cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 inhibitors, have improved the prognosis for patients with advanced melanoma. While spontaneous melanoma-associated vitiligo is a known phenomenon, the occurrence of melanoma-associated vitiligo following melanoma therapy is now recognized to associate with favorable outcomes. OBJECTIVE: The objective of this article is to provide a comprehensive literature review of melanoma-associated vitiligo and explore the insights these findings provide about the pathobiology of vitiligo and mechanisms underlying melanoma therapies. METHODS: PubMed and Science Direct databases were searched for studies pertaining to melanoma-associated vitiligo. The 36 studies reviewed included meta-analyses (n = 2), prospective cohort studies (n = 4), prospective observational studies (n = 3), retrospective studies (n = 12), case series (n = 2), and case reports (n = 13). RESULTS: The basic mechanisms underlying melanoma-associated vitiligo and vitiligo may be shared. Characterization of these mechanisms will identify new biomarkers and therapeutic targets for both melanoma and vitiligo. CONCLUSIONS: Co-opting the immune system to target tumor antigens highlights the potential overlap between anti-tumor immunity and autoimmunity. The development of vitiligo-like depigmentation in association with immunotherapy for melanoma may provide insights into both the immune response against melanoma as well as the pathogenesis of vitiligo.

Implementation of Electronic Decision Support for Diabetic Care in a Student-Run Clinic.

Background and objectives Type 2 diabetes mellitus (T2DM) is a complex disease that can lead to complications. Electronic decision support in the electronic medical record (EMR) aids management. There is no study demonstrating the effectiveness of electronic decision support in assisting medical student providers in student-run free clinics. Methods There were 71 T2DM patients seen by medical students. Twenty-three encounters used a Diabetes Progress Note (DPN) that was created from consensus, opinion-based guidelines. Each note received a total composite score based on an eight-point scale for adherence to guidelines. Statistical comparisons between mean composite scores were performed using independent t-tests. Results The mean total composite score of DPN users was significantly greater than DPN non-users (5.35 vs. 4.23, p = 0.008), with a significant difference in the physical exam component (1.70 vs. 1.31, p = 0.002). Conclusions In this exploratory study, medical student providers at an attending-supervised, student-run free clinic that used electronic decision support during T2DM patient visits improved adherence to screening for diabetic complications and standard of care.

Sexual dysfunction in men taking systemic dermatologic medication: A systematic review.

BACKGROUND: Prescription medications are among the most common causes of sexual dysfunction, and patients are often hesitant to seek help when experiencing these symptoms. OBJECTIVE: In this review, we identify the available evidence of sexual adverse effects in men using systemic dermatologic medications and suggest screening protocols and actions that may improve a patient's symptoms where possible. METHODS: A systematic review was conducted of all articles in the PubMed database published from the time of inception to May 2018 to identify studies evaluating the use of systemic dermatologic medications in men with evidence of sexual adverse effects. Subsequently, a secondary in-depth literature review was performed for each individual medication. RESULTS: There were 5497 articles reviewed in the primary systematic review, and 59 articles covering 11 systemic dermatologic medications met inclusion criteria. We identified level 1 evidence for sexual adverse effects as a primary outcome in patients taking finasteride. LIMITATIONS: Many included studies were limited by sample size and methodology. CONCLUSION: The information in this review may serve as a reference of adverse effects when deciding on a therapeutic agent and a guide to help identify patients to screen for sexual dysfunction.

Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens.

BACKGROUND: Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study. OBJECTIVE: The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California. METHODS: We performed a retrospective chart review of lung and liver transplantations to determine the incidence of post-transplant skin cancer. Participants included patients who underwent lung or liver transplantation between 2005 and 2013 at our institution. Patients included in the study were limited to those who survived through the study observation period. RESULTS: We analyzed 475 patients who underwent transplantation, including 370 liver transplant recipients and 105 lung transplant recipients. Among these, 46.3% identified as Caucasian, while 53.7% were non-Caucasian. Over a mean follow-up of 7.9 years, 11.8% of Caucasian patients developed at least one skin cancer, compared with 2.7% of non-Caucasians (p < 0.001). However, irrespective of race, skin cancer development was significantly greater in lung compared with liver transplant recipients (20.0% vs. 3.2%, p < 0.001). The standard immunosuppressive and prophylactic regimens were mycophenolate mofetil and tacrolimus based for both transplants. Mycophenolate mofetil was maintained throughout the course in lung transplant patients, whereas this agent was reduced and terminated when possible in liver transplant recipients. In addition, during the years examined, voriconazole, a known photosensitizing agent, was used in lung transplant recipients to prevent aspergillosis. CONCLUSIONS: Fair skin type increases post-transplant skin cancer development, irrespective of the immunosuppressive regimen. A higher risk of skin cancer is associated with different regimens; in particular photosensitizing agents may increase risk in transplant recipients.

The Role of Elastic Fibers in Scar Formation and Treatment.

BACKGROUND: Laser therapy is a continuously evolving treatment option for scars, and the underlying therapeutic mechanisms continue to be elucidated. OBJECTIVE: To comprehensively review the literature to summarize the role of elastin in the formation scars, as well as treatment via therapeutic lasers. METHODS: Review of the PubMED/MEDLINE database for available studies pertaining to the role of elastic fibers in scar formation and after laser-based therapy. RESULTS: The loss and disorganization of elastic fiber components plays a role in the development of atrophic, hypertrophic, and keloid scars. While the majority of histologic studies focus on the underlying changes in collagen, neoelastogenesis and reorganization of elastic fibers have also been demonstrated in studies using ablative, nonablative, and fractional laser devices for the treatment of scars. CONCLUSION: Production of novel elastin and normalization of elastic fiber organization occur after a variety of resurfacing procedures to treat scarring. As the treatment modalities to manage scars continue to evolve, further characterization of the role of elastin in the skin and in scar formation is merited.

Microneedling: A Comprehensive Review.

BACKGROUND: Microneedling is a minimally invasive procedure that uses fine needles to puncture the epidermis. The microwounds created stimulate the release of growth factors and induce collagen production. The epidermis remains relatively intact, therefore helping to limit adverse events. The indications for microneedling therapy have grown significantly, and it is becoming a more widely used treatment in dermatology. OBJECTIVE: A comprehensive review of microneedling in human subjects and its applications in dermatology. METHODS AND MATERIALS: A search was performed using PubMed/MEDLINE and Science Direct databases. Search terms included "microneedling," "needling," and "percutaneous collagen induction." All available studies involving human subjects were included in the discussion, with priority given to prospective, randomized trials. RESULTS: Studies demonstrate microneedling efficacy and safety for the treatment of scars, acne, melasma, photodamage, skin rejuvenation, hyperhidrosis and alopecia and for facilitation of transdermal drug delivery. While permanent adverse events are uncommon, transient erythema and postinflammatory hyperpigmentation are more commonly reported. CONCLUSION: Microneedling appears to be an overall effective and safe therapeutic option for numerous dermatologic conditions. Larger and more randomized controlled trials are needed to provide greater data on the use of microneedling for different dermatologic conditions in different skin types.

Literature Review of Cosmetic Procedures in Men: Approaches and Techniques are Gender Specific.

The proportion of men receiving non-surgical cosmetic procedures has risen substantially in recent years. Various physiologic, anatomic, and motivational considerations differentiate the treatments for male and female patients. Nevertheless, research regarding approaches to the male cosmetic patient is scarce. We sought to provide an overview and sex-specific discussion of the most popular cosmetic dermatologic procedures pursued by men by conducting a comprehensive literature review pertaining to non-surgical cosmetic procedures in male patients. The most common and rapidly expanding non-surgical interventions in men include botulinum toxin, filler injection, chemical peels, microdermabrasion, laser resurfacing, laser hair removal, hair transplantation, and minimally invasive techniques for adipose tissue reduction. Important sex-specific factors associated with each of these procedures should be considered to best serve the male cosmetic patient.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

CD30+ lymphoproliferative disorder with spindle-cell morphology.

Lymphomatoid papulosis (LyP) is classified as a CD30+ primary cutaneous lymphoproliferative disease. The phenotypic variability along the spectrum of CD30+ lymphoproliferative diseases is highlighted by the distinct histologic subtypes of LyP types A, B, C, and the more recently described types D, E, and F. We report the case of an elderly woman with a clinical presentation and histopathologic findings consistent with LyP, whose atypical CD30+ infiltrate uniquely demonstrated a spindle-cell morphology. To our knowledge, this is the first reported case of LyP characterized by CD30+ spindle-shaped cells, and may represent a new and distinct histologic variant of LyP.

Comparison of Childhood Vitiligo Presenting with or without Associated Halo Nevi.

BACKGROUND: Previous studies have characterized differences in vitiligo associated with halo nevi, but the features of vitiligo presenting with halo nevus in children have yet to be fully described. AIMS: We sought to provide an epidemiologic and clinical comparison of cases of childhood vitiligo presenting with or without associated halo nevi. MATERIALS AND METHODS: This was a retrospective chart review of children diagnosed with vitiligo in an academic pediatric dermatology practice from January 1990 to November 2014. The characteristics of children with vitiligo with or without associated halo nevi were compared. RESULTS: Halo nevi were identified in 55 (26%) of 208 children with vitiligo. Patients with halo nevi were significantly more likely to be male and develop vitiligo at a later age. Children with vitiligo associated with halo nevi were more likely to present with generalized vitiligo, defined according to the presence of bilateral macules. DISCUSSION: There was no significant association between groups in the percentage of body surface area with vitiligo or family history of vitiligo or autoimmune diseases. Patients with halo nevi were no more likely to develop new areas of vitiligo during the follow-up period, but there was a nonsignificant trend toward a higher rate of repigmentation in vitiligo associated with halo nevus. CONCLUSION: Halo nevi are a common finding in children with vitiligo. The presence of a halo nevus in a child with vitiligo is associated with generalized vitiligo. The presence of a halo nevus does not significantly alter the risk of disease progression and rate of treatment.

Microneedling in skin of color: A review of uses and efficacy.

In ethnic skin, traditional skin resurfacing procedures such as dermabrasion, chemical peels, and laser therapy can be effective but can also be associated with prolonged recovery and risk of complications. These complications can include a higher risk of dyspigmentation and scarring, and unsatisfactory clinical outcomes. Microneedling is an evolving treatment technique for an expanding number of dermatologic conditions. Microneedling may offer a more advantageous safety profile, particularly in the skin-of-color population (Fitzpatrick skin types IV-VI), compared with more conventional resurfacing modalities. Thus far, it has been shown to be effective for a number of dermatologic conditions in this population, including scarring, melasma, melanosis, skin rejuvenation, acne vulgaris, and primary hyperhidrosis. This article aims to provide a comprehensive review of the literature regarding the efficacy and safety of microneedling in skin of color.

Nonbacterial Causes of Lymphangitis with Streaking.

BACKGROUND: Lymphangitic streaking, characterized by linear erythema on the skin, is most commonly observed in the setting of bacterial infection. However, a number of nonbacterial causes can result in lymphangitic streaking. We sought to elucidate the nonbacterial causes of lymphangitic streaking that may mimic bacterial infection to broaden clinicians' differential diagnosis for patients presenting with lymphangitic streaking. METHODS: We performed a review of the literature, including all available reports pertaining to nonbacterial causes of lymphangitic streaking. RESULTS: Various nonbacterial causes can result in lymphangitic streaking, including viral and fungal infections, insect or spider bites, and iatrogenic etiologies. CONCLUSION: Awareness of potential nonbacterial causes of superficial lymphangitis is important to avoid misdiagnosis and delay the administration of appropriate care.