Improved Disease Control Research Articles

Role and potential of 18F-fluorodeoxyglucose-positron emission tomography-computed tomography in large-vessel vasculitis: a comprehensive review.

Large-vessel vasculitis (LVV) is a group of diseases characterized by inflammation of the aorta and its main branches, which includes giant cell arteritis (GCA), polymyalgia rheumatica (PMR), and Takayasu's arteritis (TAK). These conditions pose significant diagnostic and management challenges due to their diverse clinical presentations and potential for serious complications. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) has emerged as a valuable imaging modality for the diagnosis and monitoring of LVV, offering insights into disease activity, extent, and response to treatment. 18F-FDG-PET-CT plays a crucial role in the diagnosis and management of LVV by allowing to visualize vessel involvement, assess disease activity, and guide treatment decisions. Studies have demonstrated the utility of 18F-FDG-PET-CT in distinguishing between LVV subtypes, evaluating disease distribution, and detecting extracranial involvement in patients with cranial GCA or PMR phenotypes. Additionally, 18F-FDG-PET-CT has shown promising utility in predicting clinical outcomes and assessing treatment response, based on the correlation between reductions in FDG uptake and improved disease control. Future research should focus on further refining PET-CT techniques, exploring their utility in monitoring treatment response, and investigating novel imaging modalities such as PET-MRI for enhanced diagnostic accuracy in LVV. Overall, 18F-FDG-PET-CT represents a valuable tool in the multidisciplinary management of LVV, facilitating timely diagnosis and personalized treatment strategies to improve patient outcomes.

Rapid Detection of Viral, Bacterial, Fungal, and Oomycete Pathogens on Tomatoes with Microneedles, LAMP on a Microfluidic Chip, and Smartphone Device.

Rapid detection of plant diseases before they escalate can improve disease control. Our team has developed rapid nucleic acid extraction methods with microneedles and combined these with loop-mediated amplification (LAMP) assays for pathogen detection in the field. In this work, we developed LAMP assays for early blight (Alternaria linariae, A. alternata, and A. solani) and bacterial spot of tomato (Xanthomonas perforans) and validated these LAMP assays and two previously developed LAMP assays for tomato spotted wilt virus and late blight. Tomato plants were inoculated, and disease severity was measured. Extractions were performed using microneedles, and LAMP assays were run in tubes (with hydroxynaphthol blue) on a heat block or on a newly designed microfluidic slide chip on a heat block or a slide heater. Fluorescence on the microfluidic chip slides was visualized using EvaGreen and photographed on a smartphone. Plants inoculated with X. perforans or tomato spotted wilt virus tested positive prior to visible disease symptoms, whereas Phytophthora infestans and A. linariae were detected at the time of visual disease symptoms. LAMP assays were more sensitive than PCR, and the limit of detection was 1 pg of DNA for both A. linariae and X. perforans. The LAMP assay designed for early blight detected all three species of Alternaria that infect tomato and is thus an Alternaria spp. assay. This study demonstrates the utility of rapid microneedle extraction followed by LAMP on a microfluidic chip for rapid diagnosis of four important tomato pathogens.

Perceptions of telehealth use by PAs post-COVID-19.

Use of telemedicine and remote patient monitoring can provide significant cost savings through improved disease control and reduced exacerbations. This study investigated physician associates'/assistants' (PAs') perceptions of telemedicine to inform future use and expansion of these programs. The Telehealth Usability Questionnaire was completed by 30 PAs recruited via social media. Data were coded and analyzed through an electronic spreadsheet program. PAs generally felt that telemedicine was a helpful tool to increase access to care (M = 4.129) but did not replace in-person visits. Variation in responses related specifically to the platform indicated PAs' varying experiences about ease of use. Findings demonstrated that PAs from a variety of practice settings found telemedicine to be a helpful tool to reduce barriers and improve access to care. However, PAs did not feel that telemedicine replaces in-person visits.

Buruli ulcer, tuberculosis and leprosy: Exploring the One Health dimensions of three most prevalent mycobacterial diseases: A narrative review.

The literature review was conducted using the online databases PubMed, Scopus, ProQuest and Google Scholar, reviewing articles that were written in English in the last 15 years. Grey literature, published by intergovernmental agencies, was also reviewed. For the pathogen of Buruli ulcer, evidence suggests possums as a possible animal reservoir and thus having an active role in disease transmission to humans. Cattle and some wildlife species are deemed as established animal reservoirs for tuberculosis pathogens, with a non-negligible proportion of infections in humans being of zoonotic origin. Armadillos constitute an established animal reservoir for leprosy pathogens with the transmission of the disease from armadillos to humans being deemed possible. Lentic environments, soil and other aquatic sources may represent further abiotic reservoirs for viable Buruli ulcer and leprosy pathogens infecting humans. Ongoing investigation and implementation of public health measures, targeting (sapro)zoonotic transmission can be found in all three diseases. Buruli ulcer, tuberculosis and leprosy exhibit important yet still poorly understood One Health aspects. Despite the microbiological affinity of the respective causative mycobacteria, considerable differences in their animal reservoirs, potential environmental sources and modes of zoonotic transmission are being observed. Whether these differences reflect actual variations between these diseases or rather knowledge gaps remains unclear. For improved disease control, further investigation of zoonotic aspects of all three diseases and formulation of One Health relevant interventions is urgently needed.

Targeted Chemical Strategies in Planting Holes: A Proactive Approach to Managing Phytophthora Crown Rot of Strawberry

Phytophthora crown rot (PhCR) of strawberry, most commonly caused by P. cactorum, is introduced in annual cropping systems on quiescently infected transplants. In Florida, preventative chemical treatments are applied through drip tapes promptly after plant establishment. Since strawberry plants are especially vulnerable to PhCR during the establishment period, delaying fungicide treatments can result in stand loss, reduced productivity and suboptimal fungicide efficacy. This project evaluated the effectiveness of applying Ridomil Gold® and Orondis® Gold directly to planting holes prior to transplanting. Results from trials over four growing seasons (2019–2024) demonstrated that fungicides applied in planting holes consistently reduced PhCR incidence and progression as effectively or more than products applied via drip. These findings suggest that direct in-hole fungicide application could be an alternative for managing PhCR in strawberry. These findings warrant further research into dosage and volume optimization, and the development of precision hole-punch applicators. Such technology could lead to more strategic fungicide use by placing the treatment only where needed, i.e. the root zone, and at the crucial timing of planting establishment. It also has the potential to improve disease control outcomes, enhance productivity, and reduce the need for further fungicide applications to control PhCR, thereby decreasing the risk of resistance development to key fungicides.

A cross-sectional study on the self-management of asthma and asthma control among adult asthmatic patients in the Aseer region, KSA

Proper management of asthma is crucial for maintaining control over the disease and has a significant impact on the patient’s overall condition. The purpose of this study was to determine the extent of self-management and the level of Asthma control in the patients from the Aseer region of Saudi Arabia, as well as to investigate determinants of illness control. A study was conducted using quantitative cross-sectional methods. Researchers utilised a web-based, self-administered structured questionnaire to gather data. The questionnaire included three sections: a socio-demographic section, an Asthma Self-Management Questionnaire (ASMQ), and Asthma Control Test (ACT). An analysis using the chi-square test was conducted to determine if there was a notable connection between the socio-demographic characteristics of the participants and the level of asthma control. A total of 305 responses were collected. The average score for the Asthma Self-Management Questionnaire was 5.72, which corresponds to 40.9%. Based on the scores from the Asthma Control Test, it was found that 60 patients (20.0%) had asthma that was not under control, 94 (30.0%) had asthma that was partially controlled, and 151 (50.0%) had asthma that was well controlled. Factors such as gender, non-smoking status, and having asthma for over 10 years (p ˂0.05) were found to be strongly correlated with improved disease control. Significant gaps were found in patients’ awareness of the most important and critical aspects concerning the condition, medications, and preventative actions that limit asthma aggravation. To address the current situation, hospitals and clinics must make substantial efforts.

Development of Tools to Detect and Identify Strains Belonging to the Pseudomonas syringae Species Complex Responsible for Vein Clearing of Zucchini

Vein clearing of zucchini (VCZ) is a disease caused by seedborne bacteria that affects young plants of Cucurbita pepo subsp. pepo. VCZ agents are distributed into four phylogenetic clusters within clades 2a and 2ba of phylogroup 2 of the Pseudomonas syringae species complex. All these strains are pathogenic to squash, but only certain strains can also attack melon and cucumber. Strains belonging to clades 2b and 2d are sometimes isolated from zucchini seeds but have not been associated with VCZ epidemics. Identification tools for VCZ agents are required to improve disease control. Primers were designed to implement a seven-gene multilocus sequence analysis (MLSA) scheme for a collection of 60 strains isolated from zucchini seeds. The MLSA showed a clear predominance of strains of cluster 2ba-A and the presence of VCZ strains in a fifth cluster (2ba-C). PCR tests were designed to characterize strains in the VCZ clusters, and a multiplex qPCR test was proposed to distinguish strains with a cucurbit host range extended to melon and cucumber, harboring hopZ5 and sylC, from other strains harboring avrRpt2 and sylC. Additional qPCR tests were also designed to gain insights into clade-2b and -2d strains that can be isolated from cucurbits. These tools evaluated in silico with the NCBI database and experimentally with a collection of 112 strains detected all target strains, except for the test dedicated to clade-2b strains, and excluded 96.7 to 100% of nontarget strains. These tools are intended to serve phylogenetic studies, epidemiological monitoring, and seed testing. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Security Risk Assessment of IoT for Remote Patient Monitoring System

Remote Patient Monitoring (RPM), an essential component of telehealth, is among the biggest changes marked in healthcare. It facilitates patients’ treatment, remotely at home or in some distant location, without traditional clinical settings. The RPM plays a key role in data acquisition, data analysis and insights, and improved healthcare management. It collects real-time data using wearable sensors and mobile apps, and furnish crucial health metrics. Advanced algorithms and prognostic modelling than process the data, pattern and likely health risks to predict any disease more precisely and accurately for early action. RPM provides real-time watch and remote consultation that help in improved disease control and better patients’ care. Improved accuracy, reduced cost, real time interaction, and refined patient well-being are the significant healthcare benefits of RPM. Prognosis Health & Management (PHM) system is used for predicting the remaining useful life (RUL) of healthcare assets such as sensors, pacemakers, defibrillators and other medical equipment. The PHM leads to pre-emptive maintenance, lowers downtime, and tracks the life span of such healthcare equipment. The IoT enables PHM to monitor remote assets and gather instant data to foresee the RUL of such equipment. Providing the facilitations, PHM also creates potential vulnerabilities of exposure of device, network and data, and poses data security and privacy challenges. Therefore, strong security controls are required to keep patients’ data confidential and safe from uneven approaches to technology and data breaches. This paper evaluates risk associated with RPM using OCTAVE ALLGERO, a risk assessment framework, to mitigate the data security concerns.

Optimal approaches for COVID-19 control: the use of vaccines and lockdowns across societal groups.

By March 2023, the COVID-19 illness had caused over 6.8 million deaths globally. Countries restricted disease spread through non-pharmaceutical interventions (NPIs; e.g. social distancing). More severe "lockdowns" were also required to manage disease spread. Although lockdowns effectively reduce virus transmission, they substantially disrupt economies and individual well-being. Fortunately, the availability of vaccines provides alternative approaches to manage disease spread. Yet, vaccination programs take several months to implement fully, require further time for individuals to develop immunity following inoculation, may not have complete coverage and/or may be imperfectly efficacious against the virus. Given these aspects of a vaccination programme, it is important to understand how NPIs (such as lockdowns) can be used in conjunction with vaccination to achieve public health goals. We use mathematical methods to, investigate optimal approaches for vaccination under varying lockdown lengths and/or severities to prevent COVID-19-related deaths exceeding critical thresholds. We find that increases in vaccination rate cause a disproportionate decrease in the length and severity lockdowns to keep mortality levels below a critical threshold. With vaccination, severe lockdowns can further reduce infections by up to 89%. Notably, we include simple demographics, modelling three groups: vulnerable, front-line workers, and non-vulnerable. We investigate the sequence of vaccination. One counter-intuitive finding is that even though the vulnerable group is high risk, demographically, this is a small group and critically, per person, vaccination therefore occurs more slowly. Hence vaccinating this group first achieves limited gains in overall disease control. Importantly, we conclude that improved disease control may be best achieved by vaccinating the non-vulnerable group coupled with longer and/or more severe NPIs.

Novel Approaches to Managing Patients with Relapsed and Refractory Waldenström Macroglobulinemia.

Waldenström macroglobulinemia is a rare non-Hodgkin lymphoma (NHL) characterized by lymphoplasmacytic bone marrow infiltration associated with an immunoglobulin M (IgM) monoclonal gammopathy. Over the past two decades, a number of important novel therapies have emerged for the treatment of relapsed and refractory (R/R) WM. The purpose of this review is to discuss these novel agents. Chemoimmunotherapy which formed the basis treatment for R/R WM is slowly being replaced by novel targeted agents. These therapies, including Bruton's tyrosine kinase inhibitors, proteasome inhibitors, and B-cell lymphoma 2 inhibitors, have widened the landscape of management. Emerging therapies currently under investigation, such as bispecific T-cell engagers, chimeric antigen T-cell receptor therapy, and novel small molecule inhibitors, have additionally shown the potential to improve response and survival. The treatment of R/R WM has greatly evolved, in large part due to a greater understanding of the biology of WM, and the evaluation of novel targeted agents in the basket trials of NHL, showing early activity in the small WM cohorts. Combination regimens with these established and emerging novel therapies have the potential to further improve disease control and induce higher rates of deep responses. Strategies aimed at altering the disease trajectory would require randomized controlled trials to provide relevant data on optimal integration and sequencing of more effective and tolerable regimens earlier in the disease course.

Following Through: The Impact of Culinary Medicine on Mediterranean Diet Uptake in Inflammatory Bowel Disease.

The Mediterranean diet (MD) is recommended for all patients with inflammatory bowel disease (IBD) unless there is a specific contraindication. Culinary medicine has emerged as a method for improving dietary education. Patients and caregivers are often invested in making dietary changes to improve disease control. Here, we examine the dietary preferences of a group of young people with IBD and apply culinary medicine techniques with an in-person MD-focused cooking class. A survey evaluating dietary attitudes was sent to an IBD email listserv at our tertiary care center (n = 779). A validated questionnaire, the Mediterranean Diet Quality Index for Children and Adolescents was used to assess MD adherence. IBD dietitians customized 2 in-person MD-focused cooking classes, one for children 6 to 12 years of age (arm 1) and one for adolescents 13 to 17 years of age (arm 2). Baseline, 1-month follow-up, and 3-month follow-up surveys were completed. There were 112 survey responses. Participants were 67.0% male with diagnosis of Crohn's disease (50.0%), ulcerative colitis (42.0%), or IBD unclassified (8.0%). Most were managed on advanced therapies (82.0%). Most reported making decisions about diet (82.0%) in order to help with IBD, had met with a dietitian (69.0%), and were interested in learning more about the MD (55.3%). MD scores were primarily in the average (49.5%) and poor (41.1%) diet categories. Only those eating together as a family 3 or more times per week or those who had met with a dietitian scored in the optimal diet category. The median MD score at baseline was 4.5, increasing to 6.0 at 1 month and 7.0 at 3 months postintervention. Almost all (90%) would recommend cooking classes to others. Common barriers to MD uptake included lack of knowledge about which foods to prepare, concern about taste, and time to prepare food. This study showcases high patient and caregiver interest in dietary management of IBD and demonstrates efficacy of education via application of culinary medicine. Classes were well received by families and MD adherence scores increased postintervention. As patients with IBD and their families are often motivated to incorporate dietary therapy into their care, this work highlights the role of culinary medicine and value of future study.

Pathological Response and Outcomes in Patients With Metastatic Renal Cell Carcinoma (mRCC) Receiving Immunotherapy-Based Therapies and Undergoing Deferred Cytoreductive Nephrectomy (CN)

In this study we evaluated outcomes of patients with metastatic renal cell carcinoma who received immunotherapy before surgery. We found that receiving immunotherapy combinations before surgery can offer patients benefits in reducing tumor size and improving disease control. BackgroundImmunotherapy (IO) has improved outcomes for patients with metastatic renal cell carcinoma (mRCC). However, the timing of surgical intervention for cytoreductive nephrectomy (CN) is still controversial for this group of patients. Patients and MethodsWe identified patients with mRCC receiving IO-based therapies and undergoing CN. Patients were divided into 2 cohorts: those who underwent upfront CN and those who underwent deferred CN. Pathologic and radiographic features along with clinical outcomes were systematically collected. Comparisons were performed using Chi-square test, paired t-Test or Mann-Whitney-U test. Progression Free survival (PFS) and Overall Survival (OS) were estimated using the Kaplan-Meier method. ResultsFifty-one patients with mRCC were included, with a median follow-up of 21 months. 38 (74.5%) patients received IO-based therapies prior to CN, while 13 (25.5%) patients underwent up-front CN. IO-based therapies reduced median tumor size from pretreatment 10 cm to 8.6 cm post-treatment when given prior to CN. IO-TKI had a trend toward higher tumor shrinkage (-2.3 vs -1.2 cm). Pathologic T downstaging occurred in 42% (n=16) of patients, 11% (n=4) of whom had pT0 disease. Thrombus downstaging occurred in 13% (n=6) of patients, all with either partial response (PR) or complete response (CR) in metastases. PFS (HR=0.7, 95% CI 0.29-1.98, p=0.58) and OS (HR 0.4, 95% CI 0.13-1.57, p=0.21) were not statistically significant between 2 cohorts. ConclusionsIO-based therapies, particularly IO-TKIs, resulted in pathologic necrosis and reductions in tumor size prior to deferred CN. PFS and OS were similar for patients who received either upfront IO-based therapy or after CN.

Latest advancements in the development of new therapies for type 1 diabetes.

This study aims to explore new treatments for type 1 diabetes that could serve as an alternative or adjunct to insulin therapy. This is aliterature review based on asearch of relevant scientific articles in PubMed, Scopus, Google Scholar, and Cochrane Library databases. The scrutiny of publications revealed that the introduction of glucagon-like peptide-1 agonists into insulin therapy can improve disease control and reduce the frequency of hypoglycaemic episodes. While immune therapy is pathogenetically justified, its utility is limited in patients with recent onset of type 1 diabetes. It may, however, find application in prophylaxis in individuals at increased risk of developing this type of diabetes. Concurrently, stem cell therapy is under active investigation in clinical trials and has shown promise in reducing insulin dependence, improving β-cell function and controlling glucose levels. In addition, stem cells have demonstrated efficacy in treating complications of diabetes such as diabetic nephropathy, peripheral neuropathy and diabetic angiopathy. There is compelling evidence supporting the significant potential of gene-editing technology. Intravenous administration of T-regulatory cells, as one method of cell therapy, shows potential in stabilising the course of diabetes and slowing its progression. However, further research is warranted to confirm efficacy. While gene therapy holds promise, much of its research is currently in the preclinical stage. Further development of innovative therapies for type 1 diabetes has the potential to enhance the quality of life of patients, improve disease control and prevent the development of complications (Fig. 1, Ref. 54). Keywords: diabetes type 1, treatment, cell therapy, insulin, pancreatic β-cells.

Immunotherapy for pediatric low-grade gliomas.

Pediatric low-grade gliomas (pLGGs) are the most common brain tumor types affecting children. Although gross-total resection remains the treatment of choice, many tumors are not amenable to complete removal, because they either involve midline structures, such as the optic chiasm or hypothalamus, and are not conducive to aggressive resection, or have diffuse biological features and blend with the surrounding brain. Historically, radiation therapy was used as the second-line option for disease control, but with the recognition that this often led to adverse long-term sequelae, particularly in young children, conventional chemotherapy assumed a greater role in initial therapy for unresectable tumors. A variety of agents demonstrated activity, but long-term disease control was suboptimal, with more than 50% of tumors exhibiting disease progression within 5 years. More recently, it has been recognized that a high percentage of these tumors in children exhibit constitutive activation of the mitogen-activated protein kinase (MAPK) pathway because of BRAF translocations or mutations, NFI mutations, or a host of other anomalies that converged on MAPK. This led to phase 1, 2, and 3 trials that explored the activity of blocking this signaling pathway, and the efficacy of this approach compared to conventional chemotherapy. Despite initial promise of these strategies, not all children tolerate this therapy, and many tumors resume growth once MAPK inhibition is stopped, raising concern that long-term and potentially life-long treatment will be required to maintain tumor control, even among responders. This observation has led to interest in other treatments, such as immunotherapy, that may delay or avoid the need for additional treatments. This chapter will summarize the place of immunotherapy in the current armamentarium for these tumors and discuss prior results and future options to improve disease control, with a focus on our prior efforts and experience in this field.

Efficacy comparison of fruquintinib, regorafenib monotherapy or plus programmed death-1 inhibitors for microsatellite stable metastatic colorectal cancer.

Regorafenib (R) and fruquintinib (F) are the standard third-line regimens for colorectal cancer (CRC) according to the National Comprehensive Cancer Network guidelines, but both have limited efficacy. Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair (MSS/pMMR) CRC. Due to the lack of studies comparing the efficacy between F, R, F plus programmed death-1 (PD-1) inhibitor, and R plus PD-1 inhibitors (RP), it is still unclear whether the combination therapy is more effective than monotherapy. To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC (mCRC) patients in clinical practice. A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital, and 313 MSS/pMMR mCRC patients were finally included. A total of 313 eligible patients were divided into F (n = 70), R (n = 67), F plus PD-1 inhibitor (FP) (n = 95) and RP (n = 81) groups. The key clinical characteristics were well balanced among the groups. The median progression-free survival (PFS) of the F, R, FP, and RP groups was 3.5 months, 3.6 months, 4.9 months, and 3.0 months, respectively. The median overall survival (OS) was 14.6 months, 15.7 months, 16.7 months, and 14.1 months. The FP regimen had an improved disease control rate (DCR) (P = 0.044) and 6-month PFS (P = 0.014) and exhibited a better trend in PFS (P = 0.057) compared with F, and it was also significantly better in PFS than RP (P = 0.030). RP did not confer a significant survival benefit; instead, the R group had a trend toward greater benefit with OS (P = 0.080) compared with RP. No significant differences were observed between the R and F groups in PFS or OS (P > 0.05). FP is superior to F in achieving 6-month PFS and DCR, while RP is not better than R. FP has an improved PFS and 6-month PFS compared with RP, but F and R had similar clinical efficacy. Therefore, FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.

Insulin Pump Therapy and Adverse Skin Reactions With Focus on Allergic Contact Dermatitis in Individuals Living With Diabetes Mellitus: A Systematic Review and Clinical-Based Update

Background: The use of insulin pumps (continuous subcutaneous insulin infusion [CSII]) in individuals living with type 1 diabetes (T1D) improves disease control. However, adverse skin reactions may hamper compliance. We aimed to assess the relationship of insulin pumps, particularly that of infusion set therapy, used in children and adults with T1D and dermatitis including allergic contact dermatitis (ACD). Methods: A systematic search of PubMed, and EMBASE, of full-text studies reporting dermatitis in persons with diabetes using a CSII was conducted from 2020 to 2023. The Newcastle-Ottawa Scale was used to assess study quality. The inventory performed at the Department of Occupational and Environmental Dermatology, Malmö, Sweden (YMDA) was also performed highlighting the diagnostic process. Results: Among the 391 screened abstracts, 21 studies fulfilled the inclusion criteria. Seven studies included data on children only, four studies were on adults, and nine studies reported data on both children and adults. Participants were exposed to a broad range of pumps. Dermatitis was rarely specified. Up to 60% of those referred to a university hospital due to skin reactions possibly related to insulin pumps had an ACD. Conclusions: The review and our findings indicate that there is not sufficient focus on contact allergy in the primary toxicological evaluations of substances used also for insulin pump therapy products and that possible adverse skin reactions are not correctly followed up in the clinical setting.

Molecular characterisation of fowl adenovirus associated with hydropericardium hepatitis syndrome in broiler and layer breeders in Azerbaijan

BackgroundFowl adenovirus-4 is a causative agent of hydropericardium hepatitis syndrome (HHS) in chickens and has been frequently reported from many countries. Fowl adenoviruses cause severe disease and mortality in broiler and layer breeders in Azerbaijan. Therefore, in this study, pathological lesions and the dissemination of fowl adenovirus-4 into the visceral organs of infected birds were investigated as well as molecular characterisation of detected strains. For this, liver, heart and spleen from 20 necropsied chickens originated from a broiler breeder flock and a layer breeder flock were embeded on the FTA cards and the samples were analysed for adenovirus-DNA by PCR and sequencing.ResultsThe findings of necropsy in both broiler and layer breeder chickens were similar, and the liver was severely effected showing hepatitis, and the heart with hydropericardium lesions. The kidneys were swollen with haemorrhages and small white foci on the surface of the spleens were noted. Intestinal congestion and ecchymotic hemorrhages were also observed in some birds. Fowl adenovirus-4-DNA was detected by PCR in all collected organs of 20 birds. The sequence analysis revealed that fowl adenovirus-4 present in Azerbaijan and close similarity of the hexon genes of the adenoviruses existing in the Middle East, North America, far east and Indian subcontinent were determined by phylogenetic analysis. However, sequence diversity was detected from the adenovirus strains circulating in Europe, North and South America.ConclusionsThis study indicates the impact of fowl adenovirus-4 on the poultry health and production, and improved disease control and prevention strategies are necessary to reduce the HHS disease in chickens in Azerbaijan.

Emerging drugs in breast cancer: a focus on antibody–drug conjugates and novel treatment options in luminal disease

SummaryRecent years have seen the introduction of several new drugs and novel treatment approaches in early and advanced-stage breast cancer, leading to relevant improvements in outcome. Still, further reduction of recurrence risk in high-risk early breast cancer is required as is further improvement of disease control in metastatic disease, preferentially with parallel improvement of tolerability. Several antibody–drug conjugates are currently under clinical development, among them drugs targeting HER2, HER3 and TROP2; in addition, bispecific HER2-directed antibodies are a promising class of drugs. In hormone receptor-positive disease, optimizing treatment options in patients progressing on prior CDK4/6-inhibitor-based therapies is a focus of clinical research and recent developments encompass small molecule growth-factor pathway inhibitors such as the AKT inhibitor capivasertib, novel PIK3Ca inhibitors such as inavolisib as well as selective oestrogen receptor degraders and modulators. This article is intended as a short review of promising novel drugs in later clinical development in the field of breast cancer.

An updated reappraisal of dupilumab in children and adolescents with moderate-severe atopic dermatitis.

Atopic dermatitis (AD) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common inflammatory pathway in children and adolescents with AD. Anti-inflammatory drugs, mainly corticosteroids (CS) and immunomodulant agents are the primary therapeutic approach to dampening type 2 inflammation. However, AD patients may require long-term high CS doses or drug combinations with possibly significant adverse effects to achieve and maintain disease control. In this regard, the advent of biologics constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing both IL-4 and IL-13 and is approved for pediatric severe AD. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with AD. There is convincing evidence that dupilumab is safe and effective in managing AD. It can reduce skin lesions and associated itching, reduce the need for additional medications, and improve disease control and quality of life. However, a thorough diagnostic pathway is mandatory, especially considering the different AD phenotypes. The ideal eligible candidate is a child or adolescent with AD requiring systemic treatment because of severe clinical manifestations and impaired quality of life.

Evaluating antitumor activity and response determinants to trastuzumab deruxtecan in pediatric solid tumors.

10049 Background: Trastuzumab deruxtecan (T-DXd) is an anti-HER2 antibody-drug conjugate (ADC) linked to a topoisomerase inhibitor FDA-approved for several indications, including the treatment of HER2+ breast and gastric cancer. Although HER2 amplification is uncommon in pediatric cancers, recent demonstration of T-DXd efficacy in HER2-low breast cancer patients prompted us to examine the potential clinical relevance of T-DXd in pediatrics by evaluating HER2 expression and activity of T-DXd in preclinical pediatric solid tumor models. Methods: Cell viability was assessed in a panel of histologically diverse pediatric solid tumor cell lines and 2 HER2-amplified adult cancer cell lines treated with T-DXd, payload (DXd), and a control IgG-ADC. HER2 protein expression in patient-derived xenograft (PDX) tumors was evaluated by immunohistochemistry (IHC) using 5 clinically validated anti-HER2 antibodies. RNAseq was performed on clinical (n=290) and PDX (n=184) tumors to determine relative expression of ERBB2. In vivo activity of T-DXd was evaluated in osteosarcoma (OS, n=10), Wilms tumor (WT, n=1) and malignant rhabdoid tumor (MRT, n=1) PDX models and a desmoplastic small round cell tumor (DSRCT) cell line xenograft model. Differences in tumor volume and time to disease progression was assessed and compared across treatments and models. Responses were correlated with HER2 expression by IHC. Results: In vitro, HER2-amplified control cell lines demonstrated a >30-fold reduction of IC50 when comparing T-DXd to ADC control. In contrast, the ADC control IC50 was nearly identical to T-DXd across all pediatric cancer cell lines, consistent with the absence of HER2 amplification in these models. We observed focal and membranous staining of HER2 by IHC in PDXs but was quite variable across antibodies tested: WT 0-17% HER2+ cases (n=6), MRT 0-40% (n=5), DSRCT 0-33% (n=24), OS 0-7% (n=30). ERBB2 gene expression was highest in DSRCT followed by WT, OS and MRT. In vivo efficacy studies demonstrated complete and partial responses in OS, WT, and DSRCT and improved disease control rates (OS: 67%, p=0.006, Mann-Whitney; WT: 100%; DSRCT: 100%). However, T-DXd and ADC control demonstrated similar activity in all tumor types with no consistent correlation between in vivo response and HER2 expression. Consistent with these preclinical studies, 4 patients with progressive DSRCT were treated with T-DXd via compassionate/off-label access with signs of clinical and radiographic responses. Conclusions: T-DXd shows significant preclinical antitumor activity across multiple pediatric solid tumors but little correlation with HER2 expression suggesting a mechanism of action similar to the clinical activity observed in HER2-low breast cancer. Xenograft efficacy studies and preliminary clinical experience with T-DXd in DSRCT patients warrant formal clinical trial investigation in this largely incurable disease.