Carbon fibre composites: integrated electrochemical sensors for wound management

The applicability of employing a carbon fibre mesh as an electrochemical sensing substructure for assessing urate transformations within wound exudates is evaluated. Prototype sensor assemblies have been designed and their response characteristics towards uric acid and other common physiological components are detailed. Modification of the carbon fibre sensor through surface anodisation and the application of cellulose acetate permselective barriers have been shown to lead to optimized responses and much greater sensitivity (1440% increase) and specificity. These could enable the accurate periodic monitoring of uric acid in wound fluid. The performance characteristics of the composite sensors in whole blood, serum and blister fluid have been investigated

Environmental and Other Extrinsic Risk Factors Contributing to the Pathogenesis of Cutaneous T Cell Lymphoma (CTCL)

The applications of disease cluster investigations in medicine have developed rather rapidly in recent decades. Analyzing the epidemiology of non-random aggregation of patients with a particular disease fostered identification of environmental and external exposures as disease triggers and promoters. Observation of patient clusters and their association with nearby exposures, such as Dr. John Snow's astute mapping analysis in the mid-1800's, which revealed proximity of cholera patients in London to a contaminated water pump infected with Vibrio cholerae, have paved the way for the field of epidemiology. This approach enabled the identification of triggers for many human diseases including infections and cancers. Cutaneous T-cell lymphomas (CTCL) represent a group of non-Hodgkin lymphomas that primarily affect the skin. The detailed pathogenesis by which CTCL develops remains largely unknown. Notably, non-random clustering of CTCL patients was reported in several areas worldwide and this rare malignancy was also described to affect multiple members of the same family. These observations indicate that external factors are possibly implicated in promoting CTCL lymphomagenesis. Here, we review the epidemiology of CTCL worldwide and the clinical characteristics of CTCL patients, as revealed by global epidemiological data. Further, we review the known risk factors including sex, age, race as well as environmental, infectious, iatrogenic and other exposures, that are implicated in CTCL lymphomagenesis and discuss conceivable mechanisms by which these factors may trigger this malignancy

Burden and geographic distribution of oral cavity and oropharyngeal cancers in the Russian Federation

BackgroundThe global incidence of lip and oral cavity cancers (OCCs) and oropharyngeal cancers (OPCs) is steadily increasing. While tobacco and alcohol consumption are established risk factors, a considerable proportion of these cancers has become attributed to human papilloma virus (HPV) infection. We aimed to describe the occurrence and identify potential risk factors of OCCs and OPCs across the Russian Federation during 2007-2018.MethodsWe conducted an ecological analysis using publicly accessible data from the P.A. Herzen Moscow Oncology Research Institute. Incidence and mortality rates by jurisdiction were mapped for geospatial analysis. We pre-defined 11 potential contributing risk factors and used univariable and multivariable Poisson regression model with backwards stepwise variable selection to identify associated factors with OCC and OPC.ResultsA total of 190,585 individuals were diagnosed with OCCs and OPCs in Russia between 2007-2018. Non-uniform geographic distribution of cancer cases was noted where the Far Eastern Federal District had the highest rate of OCC and the Central Federal District of OPCs. Districts with high weekly alcohol consumption had significantly higher incidence and mortality rates in both sexes. Districts with high rates of daily smoking had higher incidence of OCC among females, and those with low smoking trends had lower mortality rates for OCCs and OPCs.ConclusionWe detail the burden of OCCs and OPCs across Russia, with the aim of elucidating modifiable risk factors and proposing evidence-based prevention strategies. Tobacco/alcohol sales control measures and smoking/drinking cessation programs should continue to be prioritized as public health measures, especially for females

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

Advanced therapeutic dressings for effective wound healing

Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing due to the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer reviewed literature and other publicly available sources such as the FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, surgical and traumatic wounds (e.g. accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue engineered substitutes, biomaterials based biological dressings, biological and naturally derived dressings, medicated sutures and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care

Elucidating pathogenesis and improving clinical management of benign cutaneous inflammation in urticaria and malignant inflammation in cutaneous T-cell lymphomas

Introduction: Chronic urticaria (CU) is defined when hives occur for at least 6 weeks. When no identifiable cause can be found, it is classified as chronic spontaneous urticaria (CSU). Approximately 50% of patients are now considered to have an autoimmune etiology which can be established in vivo with the use of the autologous serum skin test (ASST) or in vitro with the Basophil Activation Test (BAT) measuring CD63 expression. Because of its chronicity, CU in children results in substantial impairment of health-related quality of life (QoL). While urticaria represents benign inflammation, Cutaneous T-Cell Lymphomas (CTCL) represents malignant inflammation that is driven by neoplastic CD4+ T cells in the skin. About 20% of patients with early stage will progress and succumb to their disease. Currently, it is not possible to predict which patients will progress. It is also challenging to diagnose CTCL as it mimics benign inflammatory dermatoses. It may be possible to identify a set of molecular markers that may be used to help prognosticate and diagnose this disease. Methods: We have created a cohort of 139 children affected by CSU. All patients were followed for 2 years. We have studied the utility of BAT to help diagnose and monitor response to treatment, evaluated the natural history and assessed for predictors of disease resolution using established validated tools including the weekly urticaria activity score (UAS7) and the Chronic Urticaria quality of life questionnaire (CU-Q2oL). For CTCL research we used the RT-PCR and tested gene expression in 60 CTCL skin biopsy samples and in 11 patient-derived cell lines to discover diagnostic and prognostic markers and to gain additional insight in the molecular etiology of CTCL. We also tested the expression of Embryonic Stem Cell (ESC) genes in this cancer. Results: Based on the log-normal distribution of CD63 values in control subjects, the reference range and the cut-off for positive CD63 BAT values was established to be 1.2% to 1.8% (95%CI) and 1.8%, respectively. Children with CSU showed significantly elevated and significantly more increased BAT values as compared to healthy controls (Wilcoxon rank test p-value <0.001). In contrast, no difference was found between BAT results in controls and PU patients. Higher disease activity and treatment resistance were associated with higher BAT values. Using the BAT we documented that 57% of children in our cohort had autoimmune CSU. The rate of disease resolution was 10.3% per year. Positive BAT and basopenia were statistically associated with earlier disease resolution. CU-Q2oL at time of recruitment suggested that itch, sleep impairment and physical appearance were the most important factors affecting QoL. The mean UAS7 at first follow up was 8.23 and reduced to 3.62 on next follow up suggesting an overall good control of symptoms with current management strategies.Our research findings on CTCL demonstrated that 17 genes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, and TOX) are able to both identify patients who are at risk of progression and also distinguish CTCL from benign mimickers. Our findings for the first time demonstrated that many critical ESC genes are expressed in CTCL. Select ESC genes (OCT4, EED, TCF3, THAP11, CHD7, TIP60, TRIM28) were preferentially expressed in CTCL samples when compared to benign skin biopsies. Conclusions: Relative frequency of autoimmune urticaria in children is similar to adults and if proven in the future, may be a good prognostic factor predicting earlier disease resolution. BAT may serve as an effective laboratory tool to help diagnose autoimmune CSU and monitor response to treatment in moderate/severe cases.Our gene expression findings in CTCL, combined with other gene expression analyses, prepare the foundation for the development of personalized molecular approach toward diagnosis and prognostication of this cancer.Introduction : l'urticaire chronique (CU) est définie lorsque l'urticaire récidive durant au moins 6 semaines. Lorsqu'aucune cause ne peut être identifiée, cette condition est désignée urticaire spontanée chronique (CSU). Environ 50% des patients avec CSU sont considérés avoir une étiologie auto-immune qui peut être établie in vitro avec plusieurs tests incluant le test d'activation des basophiles (BAT) mesurant l'expression du marqueur CD63. En raison de sa chronicité, CU chez les enfants affecte considérablement la qualité de vie (QOL).Le lymphome cutané à cellules T (CTCL) représente une inflammation maligne qui est causée par les cellules T néoplasiques localisées à la peau. Environ 20% des patients au stade I ou II vont progresser et succomber à la maladie. Il n'est pas possible de prédire quels patients progresseront. Il est difficile de diagnostiquer CTCL puisqu'il mime des conditions cutanées bénignes. Méthodes : nous avons créé une cohorte de 139 enfants touchés par CU et suivi les patients pendant 2 ans. Nous avons étudié l'utilité de BAT pour diagnostiquer et surveiller la réponse au traitement. Nous avons évalué l'histoire naturelle et les facteurs prédictifs de la résolution à l'aide du score de l'activité hebdomadaire de l'urticaire (UAS7) et le questionnaire sur la qualité de vie (CU-Q2oL).Dans le projet de recherche sur le CTCL, nous avons utilisé le PCR en temps réel et l'expression des gènes sur les échantillons de peau de 60 patients atteints de CTCL et sur 11 lignées de cellules dérivées de patients avec CTCL pour découvrir de nouveaux marqueurs diagnostiques et pronostiques. Nous avons testé l'expression des gènes de cellules souches embryonnaires (ESC) dans ce cancer.Résultats : en fonction de la distribution logarithmique normale des valeurs de CD63 chez les enfants témoins, on a établi que l'intervalle de référence et le seuil positif pour le BAT utilisant l'expression du marquer CD63 sont de 1,2 % à 1,8 % (intervalle de confiance à 95 %) et 1,8 %, respectivement. Les valeurs du BAT chez les enfants avec la CSU ont été significativement plus élevés que chez les témoins sains. Il n'y avait pas de différence entre les résultats du BAT chez les témoins et les patients avec PU. Le BAT a été associé avec une maladie plus sévère et résistante au traitement. À l'aide du BAT, nous avons établi que 57 % des enfants dans notre cohorte avaient une origine auto-immune. Le taux de résolution annuel de CSU était de 10,3 %. Le résultat positif du BAT et la basopénie étaient statistiquement associés à une résolution plus rapide. Le CU-Q2oL au moment du recrutement a suggéré que la démangeaison, les troubles du sommeil et l'apparence physique sont les principaux facteurs affectant la qualité de vie chez les enfants avec la CU. Le score UAS7 a été réduit entre la première et la seconde visite de suivi (de 8.23 à 3,62) suggérant une bonne maîtrise des symptômes avec les recommandations de prise en charge actuelles.Les conclusions de notre recherche sur le CTCL ont démontré que 17 gènes (CCL18, CCL26, FYB, T3JAM, MMP12, LEF1, LCK, ITK, GNLY, IL2RA, IL26, IL22, CCR4, GTSF1, SYCP1, STAT5A, TOX) sont en mesure d'identifier les patients à risque de progression et distinguer le CTCL des imitateurs. Les gènes de la famille des cellules souches embryonnaires (ESC) sont exprimés dans le CTCL et certains de ces gènes (OCT4, EED, TCF3, THAP11, CHD7, TIP60, TRIM28) étaient absents dans les maladies bénignes.Conclusions : La fréquence relative de l'urticaire auto-immune chez les enfants est similaire à celle de l'adulte et, si confirmée par les études futures, la présence d'autoanticorps peut suggérer un meilleur prognostic avec une résolution plus rapide de la maladie. Le BAT peut aider à diagnostiquer la CU auto-immune et surveiller la réponse au traitement. Nos résultats d'expression des gènes dans le CTCL préparent le terrain pour le développement de l'approche personnalisée pour le diagnostic et le pronostic de ce cancer

Successful treatment of acrodermatitis continua of Hallopeau with tildrakizumab: A case report

Acrodermatitis continua of Hallopeau is a rare, localized variant of pustular psoriasis commonly associated with join disease and severe quality of life impairment. While there are no standard treatment guidelines, therapies used for psoriasis vulgaris are commonly tried. We report a case of severe acrodermatitis continua of Hallopeau in a patient with multiple comorbidities (advanced malignancy, recurrent empyema, psoriatic arthritis) where tildrakizumab lead to a rapid resolution of skin and joint disease which was maintained 1 year later. To date, there are only four cases reporting the use of IL-23 inhibitors class in acrodermatitis continua of Hallopeau and none for tildrakizumab. However, IL-23 inhibitors should be strongly considered among the treatment of choice for acrodermatitis continua of Hallopeau, especially in patients with ongoing malignancy and/or high risk of infections