Long-term Maintenance Strategies Research Articles

Adiponectin Resistance in Obesity: Adiponectin Leptin/Insulin Interaction.

The adiponectin (APN) levels in obesity are negatively correlated with chronic subclinical inflammation markers. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 messenger ribonucleic acid (mRNA) expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects. This is defined as APN resistance, and it is linked with insulin resistance in high-fat diet-fed subjects. The insulin-resistant group has a significantly higher leptin-to-APN ratio. The leptin-to-APN ratio is more than twofold higher in obese individuals. An increase in expression of AdipoRs restores insulin sensitivity and β-oxidation of fatty acids via triggering intracellular signal cascades. The ratio of high molecular weight to total APN is defined as the APN sensitivity index (ASI). This index is correlated to insulin sensitivity. Homeostasis model of assessment (HOMA)-APN and HOMA-estimated insulin resistance (HOMA-IR) are the most suitable methods to estimate the metabolic risk in metabolic syndrome. While morbidly obese patients display a significantly higher plasma leptin and soluble (s)E-selectin concentrations, leptin-to-APN ratio, there is a significant negative correlation between leptin-to-APN ratio and sP-selectin in obese patients. When comparing the metabolic dysregulated obese group with the metabolically healthy obese group, postprandial triglyceride clearance, insulin resistance, and leptin resistance are significantly delayed following the oral fat tolerance test in the first group. A neuropeptide, Spexin (SPX), is positively correlated with the quantitative insulin sensitivity check index (QUICKI) and APN. APN resistance together with insulin resistance forms a vicious cycle. Despite normal or high APN levels, an impaired post-receptor signaling due to adaptor protein-containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1)/APPL2 may alter APN efficiency and activity. However, APPL2 blocks adiponectin signaling through AdipoR1 and AdipoR2 because of the competitive inhibition of APPL1. APPL1, the intracellular binding partner of AdipoRs, is also an important mediator of adiponectin-dependent insulin sensitization. The elevated adiponectin levels with adiponectin resistance are compensatory responses in the condition of an unusual discordance between insulin resistance and APN unresponsiveness. Hypothalamic recombinant adeno-associated virus (rAAV)-leptin (Lep) gene therapy reduces serum APN levels, and it is a more efficient strategy for long-term weight maintenance.

Evaluating the freeze-thaw vulnerability of soapstone monuments and geoheritage sites in the Parco del Paradiso (Chiavenna, Italy).

This study investigates the vulnerability of soapstone monuments and ancient quarries in the Parco del Paradiso, Chiavenna, to freeze-thaw cycles. It employs climate-based damage functions to assess the risk of weathering-induced damage. A crucial aspect of the assessment involves the study of the homogeneity and trends in the selected climate data sources in the area of the case study. These data sources are ground-based weather stations, and in-situ installed temperature-humidity data loggers. The findings of this contribution underscore the significance of appropriately chosen reference climatic series and validation tests in ensuring the accuracy of the climate signal to analyze freeze-thaw statistics for specific cultural heritage sites. These insights are essential not only for supporting reliable assessment of the vulnerability of these invaluable heritage sites, which have played a vital role in local architecture and trade since Roman times, and for the successive development of long-term preventive conservation and maintenance strategies.

Material selection and long-term maintenance strategy of knee and hip prosthesis

Material selection and long-term maintenance strategy of knee and hip prosthesis

Sustainability and Resilience of Engineering Assets

The frequency and severity of natural or human-induced disaster events, such as floods, earthquakes, hurricanes, fires, pandemics, hazardous material spills, groundwater contamination, structural failures, explosions, etc., as well as their impacts, have greatly increased in recent decades due to population growth and extensive urbanization, among other factors. The World Bank estimates that the total cost of cities’ and communities’ vulnerability to these types of disasters could reach more than USD 300 billion per year by 2030. However, it has been argued that investment to improve the quality and resilience of engineered physical assets that are the backbone of modern societies, such as critical infrastructure, industrial facilities, and buildings, could significantly contribute to more sustainable and prosperous societies. Engineered assets are key to the delivery of essential services, such as transport, food, water, electricity supply, health and safety, etc. Some of these physical assets are integrated into asset systems and national or regional networks, with life cycles of several decades or even centuries. It is, therefore, of great importance that strategies and life cycle decisions, such as those related to short- and long-term capital investment planning, maintenance strategies, operational plans, and asset disposal, lead to the maximization of the value derived from these assets. Moreover, it is essential that the achievement of these goals is sustainable over time. Organizations dealing with engineering assets, both public and private, must, therefore, integrate sustainability and resilience concerns into everyday operations, using budgets that are often restricted, while also meeting demanding performance requirements in risky and uncertain environments. This Special Issue collates a selection of papers reporting the latest research and case studies regarding the trends and emerging strategies used to address these challenges, with contributions discussing how asset management principles and techniques can help to push the boundaries of sophistication and innovation to improve the life cycle management of engineered assets to ensure more sustainable and resilient cities and societies.

Assessing and Forecasting ISR-Affected Critical Infrastructure: State-of-the-Art and Challenges.

Internal swelling reactions (ISRs) are among the most critical deterioration mechanisms affecting infrastructure's durability worldwide. While preventative measures for new structures have been extensively explored, effective protocols for diagnosing and prognosing ISR-affected structures, especially at their early stages, are still required. Therefore, through a comprehensive bibliometric analysis, this study focuses on exploring the evolution and current methods for assessing and forecasting ISR damage in concrete structures. For diagnosis, a shift from concrete petrography and non-destructive techniques (NDTs) towards more comprehensive methods (i.e., multi-level assessment) with the stiffness damage test (SDT) and damage rating index (DRI) is observed. Moreover, it identifies the valuable inputs from residual expansion and pore solution analysis as relevant parameters for prognosis. Based on these findings, a structured management framework is proposed aiming to refine the diagnosis and prognosis processes of ISR-affected infrastructure, ultimately contributing to improved long-term structural health and maintenance strategies.

Maintenance of remission of ANCA vasculitis by rituximab based on B cell repopulation versus serological flare: a randomised trial

ObjectiveTo compare two long-term remission maintenance strategies for antineutrophil cytoplasmic antibody (ANCA) vasculitis.MethodsWe conducted a prospective, single-centre, open-label, randomised controlled trial of patients with ANCA vasculitis in remission after completing...

A Prospective Study of Preemptive Tenofovir Disoproxil Fumarate Therapy in HBsAg-Positive Patients With Diffuse Large B-Cell Lymphoma Receiving Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline. No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days). Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).

Strategic planning of sustainable maintenance in heritage school buildings: Malaysia perspectives

PurposeRetrofitting and rehabilitation are part of the conservation approach in Heritage Building Conservation Guideline 2016 in Malaysia. Heritage buildings can be retrofitted to preserve their culture and history while being given a new lease. Rehabilitation is a preservation requirement that is more flexible since it assumes that the structure has already deteriorated to the point where repairs are required to prevent further deterioration. Although the strategies of these two approaches are different, their combination resulted in sustainable heritage building maintenance. This long-term maintenance strategy is necessary, especially for Malaysia's numerous heritage schools, which have serious maintenance problems as a result of infrequent maintenance, repairs, and funding shortages.Design/methodology/approachThis study involved secondary data from an intensive literature review along with a comparative study from articles review and context analysis. A comparative study was conducted to determine the typical issue with heritage school buildings and the best maintenance practice for these structures. Finally, it involved a SWOT analysis study of retrofitting and rehabilitating heritage school buildings will be discussed in this study as well.FindingsThe findings of this study will focus on developing a strategic planning framework and maintenance for heritage school buildings in Malaysia to achieve sustainable maintenance. It will also highlight sustainable maintenance best practices for heritage school buildings in Malaysia. Finally, SWOT analysis will go over the pros and cons of retrofitting and rehabilitation for these buildings.Originality/valueThis paper put forward the requirements of strategic planning in heritage school buildings and outlines the significance of sustainable maintenance for educational buildings. It is an alternative for cost savings that has not been extensively investigated in previous studies.

A multi-objective maintenance strategy optimization framework for offshore wind farms considering uncertainty

While offshore wind energy is showing enormous potential, effective approaches to enhance its economics are being sought at the same time. The design of maintenance strategy is a type of strategic decision-making for offshore wind farms, aiming to improve energy production and reduce maintenance expenses. As a complicated and challenging task, the maintenance decision-making is confronted with various types of uncertainty in the model. The presence of uncertainty affects the estimation of maintenance performance, and renders the determined maintenance decisions sub-optimal or even inappropriate. In this paper, the authors propose an integrated decision-making framework incorporating i) a maintenance model which is applied to estimate maintenance performance, including maintenance costs and production losses, ii) a probabilistic uncertainty modelling approach which is used to characterize different types of uncertainty and a Monte Carlo method is adopted to generate stochastic scenarios, and iii) a multi-objective optimization method used to find the optimal decisions in the presence of conflict between multiple objectives. The uncertainties considered in the model include the stochastic attributes of time to failure, deviation between real and predicted failure times of components, and uncertain maintenance consequences. The proposed framework was applied in a generic 150MW-offshore wind farm located in the North sea. Results demonstrate that the deterministic scenario underestimates the maintenance costs and production losses, leading to the consequence that the developed maintenance strategy becomes unsatisfactory. A new series of solutions including priority solutions and trade-offs is provided for decision-makers to satisfy different goals while involving uncertainty. In addition, the influence of different uncertainties on the maintenance performance is quantified to assess the significance. The proposed optimization framework constitutes a useful decision-making tool to instruct the long-term maintenance strategy for offshore wind farms in a practical environment involving a high degree of uncertainty.

Optimized maintenance plan for oil and gas pipelines

Oil and gas pipelines transport millions of dollars of products every day making the optimization of their long-term maintenance strategies an essential target for practitioners. Thus, this paper aims to optimize the maintenance plan of such pipelines by maximizing their lifetime average condition with the minimum possible cost. This is achieved in three steps: (1) developing a life-cycle cost model for such pipelines to determine their net present value (NPV) based on the different rehabilitation actions applied throughout their lifetime; (2) establishing a strategy to determine the condition index of such pipelines before and after any rehabilitation action applied throughout their lifetime; and (3) formulating the optimization model and applying the elitist non-dominated sorting genetic algorithm (NSGA-II) to determine the optimum maintenance plans for such pipelines. The optimization model is applied to a real-life case study to demonstrate its applicability.

Edoxaban-based long-term antithrombotic therapy in patients with atrial fibrillation and stable coronary disease: Rationale and design of the randomized EPIC-CAD trial

BackgroundAnticoagulants are the standard therapy for patients with atrial fibrillation (AF) and antiplatelet therapy for those with coronary artery disease (CAD). However, compelling clinical evidence is still lacking regarding the long-term maintenance strategy with the combination of anticoagulant and antiplatelet drugs in patients with AF and stable CAD. DesignThe EPIC-CAD trial is an investigator-initiated, multicenter, open-label randomized trial comparing the safety and efficacy of 2 antithrombotic strategies in patients with high-risk AF (CHA2DS2-VASc score ≥ 2 points) and stable CAD (≥6 months after revascularization for stable angina or ≥12 months for acute coronary syndrome; or medical therapy alone). Patients (approximately N = 1,038) will be randomly assigned at a 1:1 ratio to (1) monotherapy with edoxaban (a non-vitamin K antagonist oral anticoagulant) or (2) combination therapy with edoxaban plus a single antiplatelet agent. The primary endpoint is the net composite outcome of death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant nonmajor bleeding at 1 year after randomization. ResultsAs of December 2021, approximately 901 patients had been randomly enrolled over 2 years at 18 major cardiac centers across South Korea. The completed enrollment is expected at the mid-term of 2022, and the primary results will be available by 2023. ConclusionsEPIC-CAD is a large-scale, multicenter, pragmatic design trial, which will provide valuable clinical insight into edoxaban-based long-term antithrombotic therapy in patients with high-risk AF and stable CAD.

Long-Term Maintenance Strategies after Pulmonary Rehabilitation: Perspectives of People with Chronic Respiratory Diseases, Informal Carers, and Healthcare Professionals.

Pulmonary rehabilitation (PR) is an effective intervention for people with chronic respiratory diseases (CRD); however, its effects fade after 6–12 months. Community-based strategies might be valuable to sustain PR benefits, but this has been little explored. People with CRD, informal carers, and healthcare professionals (HCPs) were recruited from pulmonology appointments of two local hospitals, two primary care centres, and one community institutional practice and through snowballing technique. Focus groups were conducted using a semi-structured guide. Data were thematically analysed. Twenty-nine people with CRD (24% female, median 69 years), 5 informal carers (100% female, median 69 years), and 16 HCPs (75% female, median 36 years) were included. Three themes were identified: “Maintaining an independent and active lifestyle” which revealed common strategies adopted by people with “intrinsic motivation and professional and peer support” as key elements to maintain benefits, and that “access to information and partnerships with city councils’ physical activities” were necessary future steps to sustain active lifestyles. This study suggests that motivation, and professional and peer support are key elements to maintaining the benefits of PR in people with CRD, and that different physical activity options (independent or group activities) considering peoples’ preferences, should be available through partnerships with the community, namely city councils.

Case Studies on the Motivation and Performance of Contributors Who Verify and Maintain In-Flux Tabular Datasets

The life cycle of a peer-produced dataset follows the phases of growth, maturity, and decline. Paying crowdworkers is a proven method to collect and organize information into structured tables. However, these tabular representations may contain inaccuracies due to errors or data changing over time. Thus, the maturation phase of a dataset can benefit from the additional human examination. One method to improve accuracy is to recruit additional paid crowdworkers to verify and correct errors. An alternative method relies on unpaid contributors, collectively editing the dataset during regular use. We describe two case studies to examine different strategies for human verification and maintenance of in-flux tabular datasets. The first case study examines traditional micro-task verification strategies with paid crowdworkers, while the second examines long-term maintenance strategies with unpaid contributions from non-crowdworkers. Two paid verification strategies that produced more accurate corrections at a lower cost per accurate correction were redundant data collection followed by final verification from a trusted crowdworker and allowing crowdworkers to review any data freely. In the unpaid maintenance strategies, contributors provided more accurate corrections when asked to review data matching their interests. This research identifies considerations and future approaches to collectively improving information accuracy and longevity of tabular information.

CFM: a database of experimentally validated protocols for chemical compound-based direct reprogramming and transdifferentiation

Cell fate engineering technologies are critically important for basic and applied science, yet many protocols for direct cell conversions are still unstable, have a low yield and require improvement. There is an increasing need for a data aggregator containing a structured collection of protocols - preprocessed, verified, and represented in a standardized manner to facilitate their comparison, and providing a platform for the researchers to evaluate and improve the protocols. We developed CFM (cell fate mastering), a database of experimentally validated protocols for chemical compound-based direct reprogramming and direct cell conversion. The current version of CFM contains 169 distinct protocols, 113 types of cell conversions, and 158 small molecules capable of inducing cell conversion. CFM allows stem cell biologists to compare and choose the best protocol with high efficiency and reliability for their needs. The protocol representation contains PubChem CIDs and Mechanisms Of Action (MOA) for chemicals, protocol duration, media , and yield with a comment on a measurement strategy. Ratings of the protocols and feedback from the community will help to promote high-quality and reproducible protocols. We are committed to a long-term database maintenance strategy. The database is currently available at https://cfm.mipt.ru}{cfm.mipt.ru

Reliability Dynamic Analysis by Fault Trees and Binary Decision Diagrams

New wind turbines are becoming more complex and reliability analysis of them rising in complexity. The systems are composed of many components. Fault tree is used as an useful tool to analyze these interrelations and provide a scheme of the wind turbine, to get a quick overview of the behavior of the system under certain conditions of the components. However, it is complicated and in some cases not possible, to identify the conditions that would generate a wind turbine failure. A quantitative and qualitative reliability analysis of the wind turbine is proposed in this study. Binary decision diagrams are employed as a suitable and operational method to facilitate this analysis and to get an analytical expression by the Boolean functions. The size of the binary decision diagram, i.e., the computational cost for solving the problem, has an important dependence on the order of the components or events considered. Different heuristic ranking methods are used to find an optimal order or one closed, and to validate the results: AND, level, top-down-left-right, deep-first search and breadth-first-search. Birnbaum and criticality importance measures are proposed to evaluate the relevance of each component. This analysis leads to classify the events according to their importance with respect to the probability of the top event. This analysis provides the basis for making medium and long-term maintenance strategies.

Novel Therapeutic Approaches and Targets for Treatment of Vulvar Lichen Sclerosus.

Vulvar Lichen Sclerosus (VLS) is a chronic inflammatory disease with a huge impact on a person's quality of life. A correct therapy is required for relieving symptoms, reversing signs and preventing further anatomical changes. The main objective of the present paper is to provide suggestions for the best treatment approach, based on the available evidence. Treatment strategies are divided on the basis of the treatment phase, distinguishing options for initial, acute or attack treatment and those for long-term, maintenance treatment. An electronic search was performed using the National Library of Medicine PubMed database. All the studies evaluating treatment of vulvar lichen sclerosus published in the English literature were analyzed, including controlled studies, case series, guidelines and reviews. Current evidence identifies ultra-potent and potent corticosteroids, administered for 12 weeks, as the first-line recommended treatment for active VLS. Topical calcineurin inhibitors, tacrolimus and pimecrolimus, are effective and safe alternatives. Long-term maintenance strategies aimed at preventing recurrences are required, after the initial treatment phase. Maintenance treatment mostly consists in topical corticosteroids, administered i) on an "as needed" basis ("reactive" scheme), ii) on a continuative regimen, iii) on a low-dose, intermittent regimen ("proactive" scheme). Further investigations are needed for better defining the placement of other options within the VLS therapeutic algorithm, including retinoids, physical and systemic treatments. The available evidence provides useful indications for the management of VLS. Both the identification of new therapeutic targets and the optimization of the available options represent the main objectives of future research.

Can a Nordic diet be implemented as a new strategy for successful long-term weight loss maintenance in subjects with obesity?

AbstractIntroductionA key problem in all weight-loss programs to fight obesity is the extent to which the body weight is maintained on a long-term basis. The study examines whether the 1-year consumption of healthy Nordic foods can result in better sustainable weight control compared to a control diet.Material and methodsAfter a successful 6-week VLCD period in obese subjects (n = 80, 52 ± 10y, BMI 34.4 ± 3.1 kg/m2, 69% female; 93% completers, -10.9 ± 3.0 kg, p < 0.001), the subjects were randomized to a new Nordic diet (NND) and a traditional Nordic diet (TND) group. The following 1-year period was a body weight maintenance period where the diets were implemented ad libitum. Weight, BMI, waist circumference and sagittal abdominal diameter were measured at 0 (immediately after VLCD), 6 and 12 months. Results are reported as mean ± SEM. Differences in the anthropometric parameters between the diets at different time points compared to the start of the dietary intervention were statistically evaluated using a general linear model (GLM-ANOVA, Minitab Inc.).ResultsForty-three subjects were randomized to NND and 37 to TND. In the NND group, 31 subjects completed the 6-month visit and 30 subjects 12-month visit. In the TND group, 24 and 21 completed 6-month and 12-month visit, respectively. We observed a non-significant difference in weight change at 6 months between NND (0.04 ± 0.87kg) and TND (2.65 ± 1.08kg). At 12 months, the weight change was significantly different between the diets (NND 1.94 ± 0.99 kg and TND 5.69 ± 1.41 kg, p = 0.029, R2 = 9.39). Change in the BMI at 12 months was significantly lower for NND (0.65 ± 0.33 kg/m2) compared to TND (1.87 ± 0.46 kg/m2, p = 0.034, R2 = 8.87) but not at 6 months (0.01 ± 0.30 kg/m2 for NND and 0.84 ± 0.36 kg/m2 for TND). Differences in waist circumference (at 6 months 0.26 ± 0.93 cm for NND and 3.30 ± 1.45 cm for TND; at 12 months 1.04 ± 1.01 cm for NND and 3.85 ± 1.79 cm for TND) were not statistically different. The sagittal abdominal diameter was borderline statistically different at 6 months (NND -0.28 ± 0.29 cm and TND 0.49 ± 0.22 cm, p = 0.049, R2 = 7.09) but not at 12 months (NND 0.41 ± 0.38 cm and TND 1.23 ± + 0.42cm).ConclusionResults show a tendency that the type of diet has an impact on successful weight maintenance, with a benefit for the NND. Further statistical analyses including dietary compliance and biomarkers are needed and will be performed. Moreover, the study is ongoing with a total of 2-year follow-up.

Biomaterial-mediated reprogramming of monocytes via microparticle phagocytosis for sustained modulation of macrophage phenotype

Monocyte-derived macrophages orchestrate tissue regeneration by homing to sites of injury, phagocytosing pathological debris, and stimulating other cell types to repair the tissue. Accordingly, monocytes have been investigated as a translational and potent source for cell therapy, but their utility has been hampered by their rapid acquisition of a pro-inflammatory phenotype in response to the inflammatory injury microenvironment. To overcome this problem, we designed a cell therapy strategy where monocytes are exogenously reprogrammed by intracellularly loading the cells with biodegradable microparticles containing an anti-inflammatory drug in order to modulate and maintain an anti-inflammatory phenotype over time. To test this concept, poly(lactic-co-glycolic) acid microparticles were loaded with the anti-inflammatory drug dexamethasone (Dex) and administered to primary human monocytes for four hours to facilitate phagocytic uptake. After removal of non-phagocytosed microparticles, microparticle-loaded monocytes differentiated into macrophages and stored the microparticles intracellularly for several weeks in vitro, releasing drug into the extracellular environment over time. Cells loaded with intracellular Dex microparticles showed decreased expression and secretion of inflammatory factors even in the presence of pro-inflammatory stimuli up to 7 days after microparticle uptake compared to untreated cells or cells loaded with blank microparticles, without interfering with phagocytosis of tissue debris. This study represents a new strategy for long-term maintenance of anti-inflammatory macrophage phenotype using a translational monocyte-based cell therapy strategy without the use of genetic modification. Because of the ubiquitous nature of monocyte-derived macrophage involvement in pathology and regeneration, this strategy holds potential as a treatment for a vast number of diseases and disorders. Statement of significanceWe report a unique and translational strategy to overcome the challenges associated with monocyte- and macrophage-based cell therapies, in which the cells rapidly take on inflammatory phenotypes when administered to sites of injury. By intracellularly loading monocytes with drug-loaded microparticles prior to administration via phagocytosis, we were able to inhibit inflammation while preserving functional behaviors of human primary macrophages derived from those monocytes up to seven days later. To our knowledge, this study represents the first report of reprogramming macrophages to an anti-inflammatory phenotype without the use of genetic modification.

Innumerable squamous cell carcinomas in a Vietnam War veteran exposed to chemical defoliants

Objective. We present a successful multidisciplinary treatment approach used for a patient with rapidly developing, high-volume, and high-risk squamous cell carcinomas (SCCs), addressing short-term treatment, long-term maintenance, and appropriate preventative strategies in a difficult patient population. Case report. An immunocompetent, 84-year-old, Caucasian man with at least 30 SCCs of the scalp, head, neck, and upper extremities, including a 4-cm SCC on the vertex of the scalp infiltrating to the periosteum, presented to a cutaneous oncology clinic. Initial physical examination revealed nearly confluent, erythematous, hyperkeratotic, crusted papules and plaques on the head, neck, back, arms, and dorsal hands, all of which were clinically obvious SCC. Nonlesional skin displayed widespread epidermal dysplasia. The patient was seen by the clinic's medical oncology and dermatology teams in coordinated dual visits. The invasive scalp lesion was treated by Mohs surgery and radiation, and the large SCC and field cancerization were successfully treated with a combination of topical and intralesional 5-fluorouracil with pulsed oral capecitabine, which resulted in a significant reduction in SCC disease burden. Conclusion. Management of patients with overwhelming numbers of SCCs is extremely challenging. Combination topical and/or intralesional 5-fluorouracil and oral capecitabine may be considered as part of the management approach when mechanical destruction and surgery alone are not feasible. Multidisciplinary care coordinated between the surgeon, dermatologic oncologist, medical oncologist, and radiation oncologist is essential for providing comprehensive treatment and deploying preventative strategies in this population at high risk for metastatic SCC formation.

Omalizumab in Chronic Spontaneous Urticaria Refractory to Conventional Therapy: An Italian Retrospective Clinical Analysis with Suggestions for Long-Term Maintenance Strategies.

IntroductionOmalizumab is indicated for the treatment of patients affected by chronic spontaneous urticaria (CSU) refractory to antihistamines. The aim of this study was to assess the efficacy, safety, and recurrence of symptoms in a real-life experience of omalizumab as an add-on therapy for H1-antihistamine-refractory CSU patients (refractory CSU).MethodsA retrospective review of the clinical records of all refractory CSU treated with omalizumab at our dermatology center from June 2014 to April 2017 was performed. Patients previously treated with second-generation antihistamines at a fourfold increased dose without clinical responses at 4 weeks of treatment were selected. Omalizumab was administered at a single dosage of 300 mg every 4 weeks for 6 months. Disease severity was assessed using the 7-day Urticaria Activity Score (UAS7).ResultsEighteen patients (14 women; mean age 51 years, range 25–74) were enrolled. Mean UAS7 at baseline was 27.3 (range 15–38). Symptoms improved in all patients at 4 weeks (UAS7 = 16.1, range 0–36). Treatment was completed in 17 patients (94.4%), and among these, a complete response (UAS7 = 0) was registered in 10 patients (58.8%). Adverse events included thrombocytopenia in 1 patient (5.6%) at 16 weeks; therapy was suspended after 20 weeks and the complication was resolved, resulting in a freedom from major adverse events of 94.4%. Symptom recurrence occurred in 3 patients (17.6%) at 4, 5, and 7 months from the end of the primary therapy. Retreatment with omalizumab was successful without any adverse effects. Mean follow-up was 9.5 months (range 1–28).ConclusionAdd-on omalizumab therapy for refractory CSU in a real-life setting seems to be effective and safe with a relatively low incidence of symptom recurrence. Further research should investigate personalized omalizumab treatment dosages and administration intervals, and the identification of biomarkers for future treatment algorithms.