Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

PURPOSE: Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. METHODS: Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. RESULTS: Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). CONCLUSION: Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

New trends on personalized sunscreens.

BACKGROUND/PURPOSE: Nowadays, there are emerging trends in customized and personalized photoprotection, focusing on the innovative approaches to enhance sun protection efficacy tailored to individual needs. METHODS: We conducted an electronic search of the following databases: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Skin Group Specialised Skin Register, and TESEO. Specific search terms related to personalized photoprotection and the variables of age, genetic predisposition, skin phototype, photodermatosis, and physiological conditions such as pregnancy, as well as lifestyle habits were used. RESULTS/CONCLUSION: The article highlights the challenges and opportunities in adopting personalized photoprotection strategies, aiming to promote skin health and prevent the harmful effects of UV radiation in the era of precision medicine.

Application of dermoscopy and reflectance confocal microscopy in vivo in the evaluation of nevi in children.

BACKGROUND: Melanocytic nevi are frequently observed in the pediatric population. While newly acquired nevi can appear during childhood, congenital nevi can continue to grow and clinically change, making patient caregivers concerned. Reflectance confocal microscopy (RCM) in vivo is a noninvasive tool that might enhance the diagnostic accuracy of dermoscopy, reducing the rate of unnecessary surgical procedures. This study aimed to assess the utility of RCM in increasing the diagnostic accuracy of pediatric melanocytic nevi that show pigmentation changes or grow rapidly. METHODS: Pediatric patients who presented between January 2022 and February 2023 in a single institution with rapidly growing melanocytic nevi or nevi that presented changes in the pigmentation were included in the study. All nevi were evaluated by means of dermoscopy and RCM. RESULTS: Forty-two patients with a total of 42 melanocytic nevi were included. Most lesions showed a honeycombed pattern (n = 21, 50%). On RCM, only 3 of 42 nevi presented atypical cells within the epidermis (7.1%). Evaluation of the dermoepidermal junction (DEJ) revealed the predominance of the meshwork pattern (n = 22, 52.4%). Notably, features considered significant for atypical melanocytic nevi included 9 nevi with scant atypical melanocytes (21.4%) and 3 nevi with nonedge papillae (7.1%). None of the studied lesions required biopsy among this cohort. CONCLUSIONS: Most rapidly growing and clinically changing nevi rarely exhibit single atypical cells in the DEJ. The RCM served as a valuable adjunct to dermoscopy, allowing reassurance in the evaluation of these lesions.

Disappearing choroidal mass: Ophthalmic manifestations of a Presumed Kikuchi-Fujimoto disease.

PURPOSE: to report our findings in a patient with presumed Kikuchi-Fujimoto disease. METHODS: report of clinical findings, fundus images, OCT, and ultrasonography. RESULTS: a 19-year-old female patient who presented with an unusual form of symptoms that fit a disease called Kikuchi-Fujimoto disease (KFD). A large choroidal mass was observed in the posterior pole, a month later the mass was completely gone. CONCLUSION: large choroidal masses can occur in patients with Kikuchi-Fujimoto disease, these do not warrant treatment as they are self-limiting.

International expert recommendations on image acquisition for in vivo reflectance confocal microscopy of cutaneous tumors.

BACKGROUND: No international recommendations exist for a minimum imaging requirement per lesion using reflectance confocal microscopy (RCM). This may be beneficial given the increasing use of remote RCM interpretation internationally. OBJECTIVE: To develop international expert recommendations for image acquisition using tissue-coupled RCM for diagnosis of cutaneous tumors. METHODS: Using a modified Delphi approach, a core group developed the scope and drafted initial recommendations before circulation to a larger group, the Cutaneous Imaging Expert Resource Group of the American Academy of Dermatology. Each review round consisted of a period of open comment, followed by revisions. RESULTS: The recommendations were developed after 5 alternating rounds of review among the core group and the Cutaneous Imaging Expert Resource Group. These were divided into subsections of imaging personnel, recommended lesion criteria, clinical and lesion information to be provided, lesion preparation, image acquisition, mosaic cube settings, and additional captures based on lesion characteristics and suspected diagnosis. LIMITATIONS: The current recommendations are limited to tissue-coupled RCM for diagnosis of cutaneous tumors. It is one component of the larger picture of quality assurance and will require ongoing review. CONCLUSIONS: These recommendations serve as a resource to facilitate quality assurance, economical use of time, accurate diagnosis, and international collaboration.

Handheld cross-polarised microscope for imaging individual pigmented cells in human skin in vivo.

We present the development of a simple, handheld cross-polarised microscope (CPM) and demonstration of imaging individual pigmented cells in human skin in vivo. In the CPM device, the cross-polarised detection approach is used to reduce the specular reflection from the skin surface and preferentially detect multiply-scattered light. The multiply-scattered light works as back illumination from within the tissue towards the skin surface, and superficial pigment such as intraepidermal melanin absorbs some spectral bands of the multiply-scattered light and cast coloured shadows. Since the light that interacted with the superficial pigment only needs to travel a short distance before it exits the skin surface, microscopic details of the pigment can be preserved. The CPM device uses a water-immersion objective lens with a high numerical aperture to image the microscopic details with minimal spherical aberrations and a small depth of focus. Preliminary results from a pilot study of imaging skin lesions in vivo showed that the CPM device could reveal three-dimensional distribution of pigmented cells and intracellular distribution of pigment. Co-registered CPM and reflectance confocal microscopy images showed good correspondence between dark, brown cells in CPM images and bright, melanin-containing cells in reflectance confocal microscopy images.

Clinical Applications of Polypodium leucotomos (Fernblock®): An Update.

Exposure to sun radiation leads to higher risk of sunburn, pigmentation, immunosuppression, photoaging and skin cancer. In addition to ultraviolet radiation (UVR), recent research indicates that infrared radiation (IR) and visible light (VIS) can play an important role in the pathogenesis of some of these processes. Detrimental effects associated with sun exposure are well known, but new studies have shown that DNA damage continues to occur long after exposure to solar radiation has ended. Regarding photoprotection strategies, natural substances are emerging for topical and oral photoprotection. In this sense, Fernblock®, a standardized aqueous extract of the fern Polypodium Leucotomos (PLE), has been widely administered both topically and orally with a strong safety profile. Thus, this extract has been used extensively in clinical practice, including as a complement to photodynamic therapy (PDT) for treating actinic keratoses (AKs) and field cancerization. It has also been used to treat skin diseases such as photodermatoses, photoaggravated inflammatory conditions and pigmentary disorders. This review examines the most recent developments in the clinical application of Fernblock® and assesses how newly investigated action mechanisms may influence its clinical use.

The Distinctive Features behind the Aggressiveness of Oral and Cutaneous Squamous Cell Carcinomas.

Squamous cell carcinomas arise from stratified squamous epithelia. Here, a comparative analysis based on recent studies defining the genetic alterations and composition of the stroma of oral and cutaneous squamous cell carcinomas (OSCC and CSCC, respectively) was performed. Both carcinomas share some but not all histological and genetic features. This review was focused on how mutations in tumor suppressor genes and protooncogenes cooperate to determine the differentiation, aggressiveness, and metastatic potential of OSCC and CSCC. In fact, driver mutations in tumor suppressor genes are more frequently observed in OSCC than CSCC. These include mutations in TP53 (encoding pP53 protein), CDKN2A (encoding cyclin dependent kinase inhibitor 2A), FAT1 (encoding FAT atypical cadherin 1), and KMT2D (encoding lysine methyltransferase 2D), with the exception of NOTCH (encoding Notch receptor 1), whose mutation frequency is lower in OSCC compared to CSCC. Finally, we describe the differential composition of the tumor microenvironment and how this influences the aggressiveness of each tumor type. Although both OSCC and CSCC tumors are highly infiltrated by immune cells, high levels of tumor-infiltrating lymphocytes (TILs) have been more frequently reported as predictors of better outcomes in OSCC than CSCC. In conclusion, OSCC and CSCC partially share genetic alterations and possess different causal factors triggering their development. The tumor microenvironment plays a key role determining the outcome of the disease.

Introduction to the Special Issue on "Keratinocyte Carcinomas: Biology and Evolving Non-Invasive Management Paradigms".

Keratinocyte carcinomas (KCs) are the most prevalent form of cancer worldwide, and their incidence is rising dramatically, with an increasing trend in recent years [...].

Psychogeriatric care in times of COVID. Lessons learned and proposals for similar situations.

The objective is to describe the problems related to outpatient psychogeriatric care in the context of the SARS-CoV-2 pandemic, as well as the proposed and implemented solutions for optimizing care for elderly people with mental disorders during the pandemic, that can also be applied in emerging similar situations in the future.

The combination of oral and topical photoprotection with a standardized Polypodium leucotomos extract is beneficial against actinic keratosis.

INTRODUCTION: This study describes a prospective, multicentre, randomized controlled, open-label study with three arms aimed at studying the differences between: [Cnt], self-administered sun protection; [T], topical treatment; and [TO], topical + oral treatment; for the management of Actinic Keratosis (AK) in a cohort of subjects of advanced age displaying severe actinic damage (SAD). METHODS: Treatments administered to groups [T] and [TO] had a common component, which is a botanical extract, Fernblock, with demonstrated photoprotective activity. RESULTS: In total, 131 subjects were distributed randomly in the three groups, and followed up clinically at three separate time points, beginning of the study (t = 0) and after 6 and 12 months. Analysis of clinical data and examination using reflectance confocal microscopy (RCM) revealed that group [T] and [TO] displayed decreased clinical AK and field cancerization parameters, including the number of new lesions, and reduced the need for additional interventions in these patients. RCM revealed normalization of the keratinocyte layer. Improvements in AK and field cancerization parameters were greatest in the group [TO], suggesting that topical and oral photoprotection improves the clinical and anatomical outcome compared to control conditions. CONCLUSIONS: The combination of topical and oral immune photoprotection provides an advantage compared to topical photoprotection alone.

Blood donor notification rate in a blood bank in Veracruz, Mexico.

Blood banks are primarily responsible for providing safe blood, but they also indirectly act to prevent the spread of infectious diseases by notifying blood donors of positive screening results. The notification process differs between countries and notifications rates are generally low. This study sought to analyze the notification rate of healthy and infection-positive donors who donated blood at CETS-Veracruz. A total of 41790 donors were analyzed, 1585 (3.79%) were positive for one or more of the screened infection markers. Only 4163 (9.96% of the total) were notified about their serology results. Of the positive donors, 157 were contacted by phone call; of them, 91 (57%) returned to the blood bank for their results. The average notification rate for positive donors was only 17.48%. The highest notification rate was for anti-HBc (26.63%), while the lowest was for HBsAg (4.17%). Age significantly influenced the return of donors: Those aged 18-24 and 25-39 years were 4.71 and 1.64 times less likely, respectively, to return for their results compared to the rate for all ages. The advice received in the pre-donation stage about the risks of transfusion-transmitted infections and the relevance of returning for results did not appear to impact donors, since the rate of notification was lower than those reported internationally. These data indicate that CETS-Veracruz should improve donor data registration and communication mechanisms to increase the notification rate, and that donor notification studies should be carried out in other Mexican blood banks to analyze the return rate at the national level.

Simulación y optimización de sistemas de vacunación con capacidad finita / Simulation and optimization of systems vaccination with finite capacity

Resumen Objetivo: Caracterizar y optimizar el flujo de pacientes dentro de un centro de vacunación, para los casos donde debe tomarse en cuenta que existe una capacidad finita en las colas frente a las estaciones. Materiales y Métodos: Se asume que los sistemas de vacunación se comportan como una red cerrada de colas con capacidad finita; para caracterizar el flujo de pacientes, se aplica simulación y un diseño experimental Box-Bhenken, donde las variables son las capacidades en las colas (buffer); posteriormente se obtienen los metamodelos del tiempo de ciclo y del número de pacientes vacunados, finalmente se calcula la asignación óptima de los lugares en las colas aplicando programación matemática. Resultados: Las colas de llenado de formatos, entrega de información y vacunación son las de mayor efecto sobre el tiempo de estadía; las colas de vacunación y el Triage son las de mayor efecto sobre la cantidad de pacientes vacunados.Si se maximiza la salida de pacientes, la mayor cantidad de lugares deben asignarse a la estación de vacunación y el resto de los espacios se distribuyen en las demás estaciones; por otra parte, si se minimiza el tiempo de estadía, entonces la mayor parte de los lugares se asignan a la estación Triage y a continuación a la estación de Vacunación, el resto de los espacios se asignarán dependiendo de la capacidad total del sistema. Conclusiones: Los responsables de administrar esta clase de sistemas deben definir el criterio bajo el cual deben cuantificar el desempeño del sistema de vacunación y a partir de este, gestionar y controlar el proceso. Cuando la demanda supera las expectativas y no es viable incrementar la capacidad, entonces la alternativa es optimizar el flujo controlando la cantidad de personas dentro del sistema.

Abstract Objective: Characterize and optimize the flow of patients within a vaccination center, for cases where it must be consider that there is a finite capacity in the queues in front of the stations. Materials and Methods: Vaccination systems are assumed to behave as a closed queue network with finite capacity; To characterize the flow of patients, simulation and a Box-Bhenken experimental design are applied, where the variables are the capacities in the queues (buffer); Subsequently, the metamodels of the cycle time and the number of vaccinated patients are obtained. Finally, the optimal allocation of places in the queues is calculated by applying mathematical programming. Results: The queues for filling out forms, delivery of information and vaccination are the ones with the greatest effect on the length of stay; the vaccination and triage queues have the greatest effect on the number of vaccinated patients. If the output of patients is maximized, the greatest number of places should be assigned to the vaccination station and the rest of the spaces are distributed in the other stations; On the other hand, if the length of stay is minimized, then most of the places are assigned to the Triage station and then to the Vaccination station, the rest of the spaces will be assigned depending on the total capacity of the system. Conclusions: Those responsible for managing this class of systems must define the criteria under which they must quantify the performance of the vaccination system and, based on this, manage and control the process. When demand exceeds expectations and increasing capacity is not feasible, then the alternative is to optimize flow by controlling the number of people within the system.

Tertiary lymphoid structures accompanied by fibrillary matrix morphology impact anti-tumor immunity in basal cell carcinomas.

Tertiary lymphoid structures (TLS) are specialized lymphoid formations that serve as local repertoire of T- and B-cells at sites of chronic inflammation, autoimmunity, and cancer. While presence of TLS has been associated with improved response to immune checkpoint blockade therapies and overall outcomes in several cancers, its prognostic value in basal cell carcinoma (BCC) has not been investigated. Herein, we determined the prognostic impact of TLS by relating its prevalence and maturation with outcome measures of anti-tumor immunity, namely tumor infiltrating lymphocytes (TILs) and tumor killing. In 30 distinct BCCs, we show the presence of TLS was significantly enriched in tumors harboring a nodular component and more mature primary TLS was associated with TIL counts. Moreover, assessment of the fibrillary matrix surrounding tumors showed discrete morphologies significantly associated with higher TIL counts, critically accounting for heterogeneity in TIL count distribution within TLS maturation stages. Specifically, increased length of fibers and lacunarity of the matrix with concomitant reduction in density and alignment of fibers were present surrounding tumors displaying high TIL counts. Given the interest in inducing TLS formation as a therapeutic intervention as well as its documented prognostic value, elucidating potential impediments to the ability of TLS in driving anti-tumor immunity within the tumor microenvironment warrants further investigation. These results begin to address and highlight the need to integrate stromal features which may present a hindrance to TLS formation and/or effective function as a mediator of immunotherapy response.

Tumor microenvironment in non-melanoma skin cancer resistance to photodynamic therapy.

Non-melanoma skin cancer has recently seen an increase in prevalence, and it is estimated that this grow will continue in the coming years. In this sense, the importance of therapy effectiveness has increased, especially photodynamic therapy. Photodynamic therapy has attracted much attention as a minimally invasive, selective and repeatable approach for skin cancer treatment and prevention. Although its high efficiency, this strategy has also faced problems related to tumor resistance, where the tumor microenvironment has gained a well-deserved role in recent years. Tumor microenvironment denotes a wide variety of elements, such as cancer-associated fibroblasts, immune cells, endothelial cells or the extracellular matrix, where their interaction and the secretion of a wide diversity of cytokines. Therefore, the need of designing new strategies targeting elements of the tumor microenvironment to overcome the observed resistance has become evident. To this end, in this review we focus on the role of cancer-associated fibroblasts and tumor-associated macrophages in the resistance to photodynamic therapy. We are also exploring new approaches consisting in the combination of new and old drugs targeting these cells with photodynamic therapy to enhance treatment outcomes of non-melanoma skin cancer.

Protective Effect of the Hydrophilic Extract of Polypodium leucotomos, Fernblock®, against the Synergistic Action of UVA Radiation and Benzo[a]pyrene Pollutant.

Oxidative stress is a harmful effect induced on the skin by polycyclic aromatic hydrocarbons (PAH), including benzo[a]pyrene (BaP) air pollutants. This effect is amplified by the additive damaging effect of the sun, especially through the UVA light component. Besides being one of the main compounds that make up air pollution, BaP can also be found in tar, tobacco smoke, and various foods. In addition to its direct carcinogenic potential, BaP can act as a photosensitizer absorbing sunlight in the UVA range and thus generating ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Fernblock® (FB) is an aqueous extract from the leaves of Polypodium leucotomos that has been proven to exert photoprotective and antioxidant effects on skin cells. In this study, we evaluate the potential of FB to prevent the damage induced by a combination of BaP and UVA light on human keratinocyte and mouse melanocyte cell lines (HaCaT and B16-F10, respectively). In particular, we have analyzed the capacity of FB to counteract the alterations caused on cellular morphology, viability, oxidative stress and melanogenic signaling pathway activation. Our data indicate that FB prevented cell damage and reduced oxidative stress and melanogenic signaling pathway activation caused by a combination of BaP and UVA light irradiation. Altogether, our findings support the fact that FB is able to prevent skin damage caused by the exposure to a combination of UVA and the air pollutant BaP.

Potent Virucidal Activity In Vitro of Photodynamic Therapy with Hypericum Extract as Photosensitizer and White Light against Human Coronavirus HCoV-229E.

The emergent human coronavirus SARS-CoV-2 and its high infectivity rate has highlighted the strong need for new virucidal treatments. In this sense, the use of photodynamic therapy (PDT) with white light, to take advantage of the sunlight, is a potent strategy for decreasing the virulence and pathogenicity of the virus. Here, we report the virucidal effect of PDT based on Hypericum extract (HE) in combination with white light, which exhibits an inhibitory activity of the human coronavirus HCoV-229E on hepatocarcinoma Huh-7 cells. Moreover, despite continuous exposure to white light, HE has long durability, being able to maintain the prevention of viral infection. Given its potent in vitro virucidal capacity, we propose HE in combination with white light as a promising candidate to fight against SARS-CoV-2 as a virucidal compound.

Influence of serum vitamin D level in the response of actinic keratosis to ingenol mebutate.

Vitamin D (VD) serum levels, and keratinocytic basal expression of vitamin D receptor (VDR) before treatment of actinic keratoses (AK) have been previously reported as possible biomarkers of the response of AK to treatments. We intended to evaluate the association between these and other serum and immunohistochemical parameters with the response of AK to treatment with topical ingenol mebutate (IM). Twenty-five patients with AK on the head were treated with topical IM 0.015% gel once daily for 3 days. Biopsies were taken at baseline and 6 weeks after treatment. Immunohistochemical staining was performed for VDR, P53, Ki67, Aurora B, Survivin and ß-catenin. Basal serum 25(OH)D levels were determined. IM was more effective for KIN I and II AKs than in KIN III, and histological responders showed significantly higher serum VD levels (30.278 [SD 8.839] ng/mL) than nonresponders (21.14 [SD 7.079] ng/mL, p = 0.023). In addition, mean basal expression of VDR (45.63 [SD 16.105] %) increased significantly (57.92 [SD 14.738] %, p = 0.003) after treatment with IM. A significant decrease after treatment in the expression of several markers of aggressiveness and progression to squamous cell carcinoma, namely P53, Ki-67, aurora B kinase and survivin, was also observed. Our results support a relationship between VD status and the response of AK to treatment with topical IM, suggesting that its previous correction to proper serum levels in VD-deficient patients could improve the response of AK to the treatment.

Mother and sibling interactions during the preweaning period influence myelination and impulse propagation of the sensory sural nerve in the adult rat.

To investigate whether mother and sibling interactions during the preweaning period influence the histological and electrophysiological characteristics of the sensory sural nerve (SUn) in the adult rat, litters composed of 1, 3, 6, 9, and 12 male pups (P) were formed and the pups routinely weighed until postnatal day 60 (PND60). At PND9, 3P and 6P litters showed greater body weight than pups without siblings or from 9P or 12P litters, and such differences in weight were maintained until adulthood. Analysis of maternal licking at PND8 and 9 showed that pups from large litters received fewer licks than pups from small size litters. At PND60, SUn of rats from 6P and 9P litters had greater compound action potential (CAP) amplitude and a higher proportion of axons with large myelin thickness than nerves from rats of 1P, 3P, or 12P litters. SUn of heaviest rats from 9P and 12P litters had greater CAP area and myelination than the lightest rats from the same litters. We propose that a complex interplay of sensory, social, and nutritional factors arising from mother and littermate interactions during the preweaning period influence myelination and the propagation of action potentials in the SUn of adult rats.