Prophylaxis Research Articles

Lenvatinib, sintilimab combined interventional treatment vs bevacizumab, sintilimab combined interventional treatment for intermediate-advanced unresectable hepatocellular carcinoma

BACKGROUND Bevacizumab and sintilimab combined interventional treatment (BeSiIT) and L envatinib and sintilimab combined interventional treatment (LeSiIT) are two commonly used therapeutic regimens for intermediate-advanced hepatocellular carcinoma (HCC) in clinical practice. AIM To compare the clinical efficacy and safety of BeSiIT and LeSiIT for the treatment of intermediate and advanced HCC. METHODS Patients diagnosed with intermediate-advanced HCC and initially treated with BeSiIT or LeSiIT in the Tianjin Medical University Cancer Institute and Hospital between February 2020 and July 2021 were included. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), conversion rate, and treatment-related adverse events. RESULTS Total 127 patients met the inclusion criteria and were divided into BeSiIT and LeSiIT groups. Twenty-eight and fifty patients in the BeSiIT and LeSiIT groups, respectively, were assessed after 1:2 propensity score matching. PFS and OS rates were not significantly different between the two groups. No significant variations were noted in ORRs or DCRs according to the Response Evaluation Criteria in Solid Tumors (RECIST), and modified RECIST. BeSiIT group showed a better conversion rate than the LeSiIT group (P = 0.043). Both groups showed manageable toxicity profiles. Multivariate analysis showed that the independent factors associated with PFS were alpha-fetoprotein levels and carcinoembryonic antigen score. CONCLUSION In intermediate-to-advanced HCC, the BeSiIT and LeSiIT groups exhibited acceptable toxicities and comparable PFS, OS, and ORR.

Novel insights into antioxidant status, gene expression, and immunohistochemistry in an animal model infected with camel-derived Trypanosoma evansi and Theileria annulata

Abstract Background Hemoprotozoan diseases, especially trypanosomosis and theileriosis, adversely affect the productivity, growth, and performance of camels. Regular sampling and investigation of camels are challenging due to several factors. Consequently, there is a lack of knowledge on camel parasite genotyping, cytokine production, and oxidative stress parameters during infection. Methods The present study investigated two critical blood protozoa infecting camels in Egypt, Trypanosoma evansi and Theileria annulata, using molecular methods, specifically 18S rRNA gene analysis. Following molecular confirmation, experimental infections were induced in Swiss albino mice to assess the expression of immune response genes and oxidative stress parameters. The study further explored the correlation between histopathological alterations and inflammatory reactions in the kidney, spleen, and liver of infected mice, alongside the immunohistochemical expression of caspase-3, proliferating cell nuclear antigen (PCNA), and tumor necrosis factor (TNF). Results Trypanosoma evansi and T. annulata isolated from naturally infected camels were molecularly identified and deposited in GenBank under accession numbers OR116429 and OR103130, respectively. Infection with T. evansi and T. annulata caused significant adverse effects on the immune condition of infected mice, increasing the pathogenicity of the infection. This was evidenced by a significant increase in oxidative stress parameter levels in both naturally infected camels and experimentally infected mice compared to healthy controls. Furthermore, the expression of immune response genes was significantly elevated in infected mice. Immunohistochemistry analysis showed a pronounced upregulation of caspase-3, PCNA, and TNF in the infected groups relative to the control group. These findings are the first to be reported in Egypt. Conclusions This study successfully identified and genotyped two economically important blood protozoa, T. evansi and T. annulata, from camels in Egypt. Additionally, the experimental animal model provided valuable insights into the immune response, oxidative stress, and histopathological changes induced by these parasites, demonstrating comparable results to naturally infected camels. These findings highlight the potential of this model to study parasite–host interactions and immune responses, contributing to a better understanding of the pathogenic mechanisms of T. evansi and T. annulata infections. This model may be useful for future studies focused on disease control and therapeutic interventions. Graphical Abstract

Persistent Inadequate Disease Control and Therapeutic Inertia in Moderate-to-Severe Atopic Dermatitis: A 12-month Longitudinal Analysis of Real-world Outcomes from the TARGET-DERM AD registry

Background: Therapeutic inertia refers to the delay or failure in treatment escalation in patients not achieving adequate disease control; it is a challenge in the management of moderate-to-severe atopic dermatitis (AD). Despite the availability of conventional (CST) and advanced systemic therapies (AST) utilized for the treatment of moderate to severe AD, many patients do not achieve treatment success. However, the extent of this inadequacy in real-world clinical practice remains underexplored. Objectives: This study evaluates the occurrence of therapeutic inertia and the proportion of patients with moderate-to-severe AD who continue to show inadequate response after receiving systemic therapies for a duration from 3 to 12 months Methods: We conducted a longitudinal analysis of patients with moderate-to-severe AD (vIGA-AD≥3) from the TARGET-DERM AD registry, including 3,457 participants from 39 centers in the U.S. and Canada. Eligible patients had documented outcomes at the initiation of systemic therapy and after 3 months up to 12 months of follow up. We assessed clinician- and patient-reported outcomes to identify the proportion of patients not meeting treatment targets based on expert consensus. An inadequate response was defined as not achieving a validated Investigator Global Assessment (vIGA-AD) score ≤2, a 50% improvement in Body Surface Area (BSA), and a ≥4-point reduction in the Worst Pruritus Numeric Rating Scale (WP-NRS). An optimal response was defined as a vIGA-AD score ≤1 (clear or almost clear skin), BSA ≤2%, and WP-NRS itch score of 0/1 (complete or almost complete skin resolution). Results: Out of 2,107 patients with moderate-to-severe AD, 445 met the inclusion criteria. The majority were adults (63.8%), female (62.0%), and Non-Hispanic White (45.4%), with an average age of 31 years. Most patients (88.8%) initiated treatment with AST, with dupilumab being the most common (86.5%). The mean vIGA-AD was 3.3 for AST and 3.6 for CST at initiation (P<0.01). At 6 months, 37% and 67% of AST-treated patients had inadequate responses in terms of skin clearance and itch outcomes, respectively, while 82% and 79% did not achieve optimal responses. At 12 months, these figures were approximately 30% and 66% for inadequate responses and 85% and 88% for not achieving optimal responses, respectively. CST-treated patients showed a similar trend. Conclusions: The study reveals that a significant portion of moderate-to-severe AD patients fail to achieve adequate disease control with systemic therapies over 12 months, indicating substantial presence of therapeutic inertia. These findings suggest a need for more proactive management strategies in AD treatment.

Impact of the nocebo effect on discontinuation of statin therapy due to myopathy in patients with cardiovascular disease – a review

Introduction and purpose of review: Statins are widely used drugs in the prevention of cardiovascular diseases, yet many patients experience side effects of statin use, mainly muscle symptoms, such as myopathy, which often lead to discontinuation of treatment. The aim of this literature review is to assess the role of the nocebo effect in reported muscle symptoms and its impact on statin discontinuation in patients with cardiovascular diseases. Methods: The review analysed the results of several studies, including key publications such as the N-of-1 trial by Wood et al.[1] and the work of Collins et al.[2] on the safety and efficacy of statin therapy. The review covered articles published between 2000 and 2023 that examined the impact of the nocebo effect on statin discontinuation[3-10]. Results: The collected data indicate that the nocebo effect plays a significant role in the reported muscle symptoms during statin use. The study by Wood et al.[1] showed no significant differences in reported symptoms between the groups taking statins, placebo, or receiving no treatment, suggesting that a substantial portion of the symptoms results from the nocebo effect. Similar findings were obtained in the study conducted by the StatinWISE group[4], where patients taking statins and placebo reported a comparable frequency of muscle symptoms. An analysis conducted by Collins et al.[2] indicates that the actual incidence of myopathy associated with statin therapy is much lower than commonly reported. Conclusions: The nocebo effect significantly influences the perceived adverse effects of statins, which may lead to the unjustified discontinuation of these drugs by patients with cardiovascular diseases. Further research is needed to better understand the psychological mechanisms affecting statin tolerance and to develop educational and clinical strategies aimed at minimizing the nocebo effect and improving long-term adherence to therapy.

A Scoping Review of Existing Policy Instruments to Tackle Overweight and Obesity in India: Recommendations for a Social and Behaviour Change Communication Strategy

Background The Indian government is committed to addressing various manifestations of malnutrition, including overweight and obesity, inorder to improve individual health and well-being. The scoping review aims to map existing national policy instruments (programmes, schemes, regulations and guidelines) addressing overweight and obesity in India and analysing them for Social and Behaviour Change Communication (SBCC) strategies. Methods Systematic identification and selection of policy instruments using ‘Arksey and O’Malley’ framework was conducted from central government ministry websites, between March and June 2023. These instruments focused on nutrition and/or physical activity, targeting specific demographic groups like pregnant women, lactating mothers, children (0-5 years and 5-9 years), or adolescents (10-19 years); excluding those focusing on specific diseases like micronutrient deficiencies, wasting, and stunting. Based on search strategy six policy instruments were included and analysed for SBCC strategies. Results While many policy instruments incorporated SBCC plans; the ‘National Programme for Prevention of Non-Communicable Diseases (NP-NCD)’ stands out as a significant policy initiative specifically targeting the prevention of overweight and obesity within the broader context of Non-Communicable Diseases. It adopts a comprehensive approach addressing key drivers contributing to overweight/obesity across multiple levels of behavioural influence i.e., individual, interpersonal, community and organisation for health promotion. However, there’s need to strengthen SBCC strategies related to prevention and management of obesity, especially screening and counselling, to cover all age groups with a particular focus on adolescents and youth. SBCC strategies can also be incorporated into India’s Integrated Nutrition Support Programme (POSHAN 2.0) and/or Reproductive, Maternal, New-born, Child, Adolescent Health and Nutrition (RMNCAH+N) under the National Health Mission. Conclusion This paper underscores the necessity for comprehensive strategies to address multifaceted origins of overweight and obesity. The NP-NCD stands out as a noteworthy initiative, and there is considerable potential for other programmes to emulate SBCC strategies to bolster their overall effectiveness. Note : *Policy instruments throughout the paper have been used to cover programmes, schemes, regulations and guidelines.

Activins and Inhibins in Cardiovascular Pathophysiology

Activins and inhibins, members of the transforming growth factor β (TGFβ) superfamily, were initially recognized for their opposing effects on the secretion of follicle-stimulating hormone. Subsequent research has demonstrated their broader biological roles across various tissue types. Primarily, activins and inhibins function through the classical TGFβ SMAD signaling pathway, but studies suggest that they also act through other pathways, with their specific signaling being complex and context-dependent. Recent research has identified significant roles for activins and inhibins in the cardiovascular system. Their actions in other systems and their signaling pathways show strong correlations with the development and progression of cardiovascular diseases, indicating potential broader roles in the cardiovascular system. This review summarizes the progress in research on the biological functions and mechanisms of activins and inhibins and their signaling pathways in cardiovascular diseases, offering new insights for the prevention and treatment of cardiovascular diseases.

Core Components of Cardiac Rehabilitation Programs: 2024 Update: A Scientific Statement From the American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation

The science of cardiac rehabilitation and the secondary prevention of cardiovascular disease has progressed substantially since the most recent American Heart Association and American Association of Cardiovascular and Pulmonary Rehabilitation update on the core components of cardiac rehabilitation and secondary prevention programs was published in 2007. In addition, the advent of new care models, including virtual and remote delivery of cardiac rehabilitation services, has expanded the ways that cardiac rehabilitation programs can reach patients. In this scientific statement, we update the scientific basis of the core components of patient assessment, nutritional counseling, weight management and body composition, cardiovascular disease and risk factor management, psychosocial management, aerobic exercise training, strength training, and physical activity counseling. In addition, in recognition that high-quality cardiac rehabilitation programs regularly monitor their processes and outcomes and engage in an ongoing process of quality improvement, we introduce a new core component of program quality. High-quality program performance will be essential to improve widely documented low enrollment and adherence rates and reduce health disparities in cardiac rehabilitation access.

EFFECT OF SEX AND AGE ON SURVIVAL OF ADULT CULEX TARSALIS FROM A SUSCEPTIBLE LABORATORY STRAIN EXPOSED TO PERMETHRIN IN THE CDC BOTTLE BIOASSAY

ABSTRACT This study investigates the effect of mosquito sex and age on the survival and resistance determination of adult Culex tarsalis exposed to permethrin, a pyrethroid commonly used for mosquito control, using the Centers for Disease Control and Prevention (CDC) bottle bioassay method. A permethrin-susceptible strain of Cx. tarsalis (Bakersfield strain) was used in this study. Survival was compared for young adult females (2–5 days old) relative to older adult females (7–10 days old) and separately for female and male mosquitoes of the same age (2–5 days old). Mortality was slightly higher for males than females during the first observation period (0–5 min) following permethrin exposure, and higher for older females relative to younger females from 5 to 10 min following permethrin exposure, with no differences in mortality by either sex or age for observation periods during the remainder of the diagnostic period. When evaluated over the full diagnostic period, survival varied with mosquito age but not sex. However, all mosquitoes, regardless of sex or age, died within the 30-min diagnostic period for this species, confirming their permethrin susceptibility per the CDC bottle bioassay. This research contributes valuable insight into the potential impact of sex and age on mosquito susceptibility to insecticides in the context of insecticide resistance determination.

Trends in Sickle Cell Disease Mortality: 1979–2020

BACKGROUND AND OBJECTIVES: Although sickle cell disease (SCD)-related childhood mortality in the United States significantly improved in the 1990s, unclear is the trend in SCD-related mortality more recently given the continued disparities faced by this minoritized population. In this analysis, we aimed to (1) compare the overall and age-specific mortality rates from 1999 to 2009 vs 2010 to 2020 with a particular focus on the age of transition and (2) determine the most common causes of death for the US SCD population for 2010 to 2020. METHODS: We analyzed publicly available data from the Centers for Disease Control and Prevention WONDER database, a compilation of national-level mortality statistics from 1979 to 2020 derived from death certificates compiled by the National Center for Health Statistics. We searched by all individuals of all ethnicities, sexes, and ages using the underlying cause of death. RESULTS: The crude mortality rate for individuals with SCD for 2010 to 2020 was 1.6 per 1 000 000 individuals, which was significantly lower than the period 1999 to 2009 (crude rate 1.7 per 1 000 000, P < .0001). In addition, the mean age at mortality of those with SCD was older in 2010 to 2020 (43 years) versus 1999 to 2009 (39 years). However, there remains a significant increase in mortality rate in the 20 to 24 year age group versus 15 to 19 years (1.7 per 1 000 000 versus 0.7 per 1 000 000, P < .0001), corresponding with the age of transition from pediatric to adult centers. In addition, 39% of underlying causes of death were not caused by SCD, but rather primarily chronic conditions, including cardiovascular, cerebrovascular, malignancy, and renal disease. The study has several limitations mostly because of the imperfections of administrative data sources, including inaccuracies in diagnoses codes, risking over or undercounting. CONCLUSIONS: Although the US SCD-related mortality rate continues to decrease, the age of transition to adult care is a particularly vulnerable time in the lives of this marginalized group. Innovative and expanded approaches to care are greatly needed.

Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040

ImportanceThe burden of liver cancer varies worldwide. An upward trend in both hepatocellular carcinoma (HCC) incidence and mortality in the past 2 decades has been observed.ObjectiveTo assess observed HCC-related age-standardized mortality rates (ASMRs) in the US for 2006 to 2022 and provide ASMR projections through 2040.Design, Setting, and ParticipantsThis cross-sectional study used data from the National Vital Statistics System, which is accessible through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research website. Data on deaths attributed to HCC (from January 1, 2006, to December 31, 2022) were obtained for adults 25 years or older and were stratified by liver disease etiology, age, sex, and race and ethnicity. Etiologies included alcohol-associated liver disease (ALD), hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction–associated steatotic liver disease (MASLD).Main Outcomes and MeasuresThe main outcomes were (1) observed ASMRs of HCC per 100 000 persons using Joinpoint regression (National Cancer Institute) to assess trends during 2006 to 2022 and (2) ASMRs projected for 2023 to 2040 using Prophet and AutoARIMA modeling.ResultsThis study included 188 280 HCC-related deaths from 2006 to 2022. Most deaths occurred among males (77.4%). The annual percentage change was 4.1% (95% CI, 2.2% to 7.7%) for 2006 to 2009 and decreased to 1.8% (95% CI, 0.7% to 2.0%) for 2009 to 2022, with an overall observed ASMR of 5.03 per 100 000 persons in 2022 and a projected ASMR of 6.39 per 100 000 persons by 2040, with consistent trends for both sexes. By etiology, ASMRs decreased for HCV- and HBV-related mortality but increased for ALD- and MASLD-related mortality. In 2022, MASLD surpassed HBV as the third-leading cause of HCC-related death and was projected to overtake HCV in 2032 as the second-leading cause; ALD was projected to be the leading cause of HCC-related death in 2026. In 2022, the ASMR was higher among individuals aged 65 years or older compared with those aged 25 to 64 years (18.37 vs 1.79 per 100 000 persons). The American Indian or Alaska Native population had the largest increase in projected ASMR by 2040 (14.71 per 100 000 persons) compared with the Asian population (3.03 per 100 000 persons).Conclusions and RelevanceIn this cross-sectional study, ASMRs for ALD- and MASLD-related HCC death increased rapidly from 2006 to 2022; ALD-related HCC was projected to be the leading cause by 2026, with MASLD as the second-leading cause by 2032. These findings may serve as a reference for public health decision-making and timely identification of groups at high risk of HCC death.

Development and validation of an Arabic tool for assessment of post-vaccination confidence in COVID-19 vaccines (ARAB-VAX-CONF)

Abstract Background Vaccine confidence is described as a belief that vaccines are effective, safe, and part of a trustworthy health system. The objective of this study was to develop and validate an Arabic tool to evaluate confidence in the received coronavirus disease 2019 (COVID-19) vaccines (ARAB-VAX-CONF). Methods The research team developed the ARAB-VAX-CONF based on three areas specified by the Centers for Disease Control and Prevention (CDC): confidence in vaccine effectiveness, confidence in vaccine safety, and confidence in the healthcare system. The analysis includes data from 406 eligible vaccinated persons (≥ 18 years). Cronbach’s alpha was used to measure internal consistency, while convergent, discriminant, exploratory, and confirmatory factor analyses were used to verify construct validity. Results A total of 406 adults were recruited, with a mean age of 33.0 ± 12.2 years. A total of 63.1% were males, 56.7% were married, 21.9% had chronic conditions, 93.3% were nonsmokers, and 39.6% were obligated to obtain vaccines. The three domains of the scale met the criterion of internal consistency (Cronbach’s alpha > 0.7). Convergent validity was identified by the significant inter-item and item-mean score of the domain correlation (P < 0.001). Discriminant validity was reported as the inter-factor correlation matrix (< 0.7). The Kaiser–Meyer–Olkin sampling adequacy measure was 0.80, and Bartlett’s sphericity test was significant (P < 0.001). Exploratory factor analysis indicated that the scale could be summarized into three factors. Confirmatory factor analysis confirmed the adequate psychometric properties and fit with observed data (root-mean-square error of approximation = 0.08, comparative fit index = 0.945, Tucker-Lewis index = 0.924, standardized root-mean-square residual = 0.086, normed fit index = 0.918, and goodness-of-fit index = 0.909). Conclusions The ARAB-VAX-CONF developed in this study is valid and reliable for assessing confidence in vaccine effectiveness, safety, and confidence in the healthcare system. The ARAB-VAX-CONF can support decision-makers in addressing the gap in vaccine confidence among various populations.

Management of Fusarium Wilt of Lettuce

Abstract In recent years, Fusarium wilt, caused by Fusarium oxysporum f. sp. lactucae, has become the most important lettuce disease throughout the world. Since the pathogen is seed-transmitted, the disease spreads through infected seeds, favoured by the global commerce. We describe the biology and epidemiology of the pathogen, as well as the differentiation of four physiological races, with their distribution in different geographical areas. The reaction of the lettuce types and varieties to the pathogen are also described, as well as the diagnostic tools available for an appropriate detection of the pathogen, including the races. Like other soil-borne diseases, Fusarium wilt of lettuce is difficult to manage with a single product and/or with a single approach. At present, minimizing crop losses due to Fusarium wilt on lettuce entails the deployment of all available existing disease control tools within an integrated management programme. The first preventative strategy is the use of healthy seeds. Stock seeds should be produced in the areas associated with the lowest disease risk and subjected to standardized health analysis. Furthermore, seeds should be treated with chemical/physical or biological treatments. Among chemical tools, soil disinfestation is becoming very difficult due to the loss of registered fumigants. A careful monitoring of the race situation in the field would be useful for efficient use of genetic means of control. The seed industry is investing in the search of new varieties resistant to Fusarium wilt. Looking forward, the development of commercially acceptable cultivars of desired types of lettuce with high levels of resistance to Fusarium wilt as well as refinement of existing or development of new cultural, chemical and biofungicide tools should lead to more efficient and effective disease management. Information © The Authors 2024

Impact of Therapeutic Inertia on Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis: A 12-Month Longitudinal Study from the TARGET-DERM AD Registry

Background: Therapeutic inertia, the delay or reluctance to modify treatment when goals are unmet, is a significant challenge in managing chronic diseases, including atopic dermatitis (AD). This inertia can lead to suboptimal disease control and affect patient outcomes. Objectives: This study evaluates the effect of therapeutic inertia on patient-reported outcomes (PROs) in moderate-to-severe AD patients undergoing systemic treatment over 3 to 12 months. Methods: We analyzed longitudinal data from the TARGET-DERM AD registry, which includes 3,457 patients with moderate-to-severe AD from 39 centers across the U.S. and Canada. Eligible patients had documented patient-reported outcomes (PROs) at the initiation of systemic therapy and at subsequent 3-month intervals up to 12 months of follow-up. We assessed the proportion of patients not meeting treatment targets based on expert consensus. Patients had a validated Investigator Global Assessment (vIGA-AD) score of 3 or more at initiation of either an advanced systemic therapy (AST) such as biologics or JAK inhibitors or a conventional systemic therapy (CST) such as cyclosporine, methotrexate, or prednisone. PROs were evaluated at 3-month intervals up to 12 months, assessing achievement against the predefined treatment targets. PRO measures included Worst-Itch (PROMIS Itch-Severity), POEM, PO-SCORAD, NRS-sleep, and NRS-pain with specific moderate and optimal target levels established for each. Itch-Severity (range: 0–10; moderate target: ≥4-point reduction, optimal target: score ≤1), POEM (range: 0-28; moderate target: ≥4-point reduction, optimal target: score ≤2), PO-SCORAD (range: 0-103; moderate target: score ≤24; optimal target: score ≤10), NRS-sleep and NRS-pain (range: 0-10; moderate target: reduction ≥3-points; optimal target: score ≤1). Results: Out of 2107 patients with moderate-to-severe AD, 445 qualifying participants were included (63.8% adult, 62.0% female, 45.4% Non-Hispanic White, mean age of 31 years). Most patients (88.8%) initiated AST, with dupilumab being the most common (86.5%). At 6 months, significant proportions of AST-treated patients failed to reach moderate and optimal targets for itch (67% and 79%, respectively), POEM (46% and 69%), and NRS-sleep (59% and 47%). By 12 months, these figures were similar, with 66% and 88% failing to meet itch targets, 53% and 73% failing to meet POEM targets, and 62% and 45% failing to meet NRS-sleep targets, respectively. A similar pattern was observed for other PROs. CST-treated patients exhibited similar trends. Conclusions: The study highlights the profound impact of therapeutic inertia on the quality of life of patients with moderate-to-severe AD. Despite systemic therapy, a considerable proportion failed to meet treatment targets over a 12-month period, underscoring the need for more proactive and responsive treatment strategies in AD management.

Long-Term Maintenance of Optimal Treatment Targets for Skin and Itch Outcomes With Upadacitinib in Moderate-to-Severe Atopic Dermatitis: 140-Week Results From the Phase 3 Measure Up 1 and 2 Studies

Introduction: Despite undergoing prolonged systemic therapy, many patients with moderate-to-severe atopic dermatitis (AD) do not achieve optimal targets for skin and itch outcomes as defined by Aiming High in Eczema/AD (AHEAD) recommendations (eg, ≥90% improvement from baseline in Eczema Area and Severity Index [EASI 90] and Worst Pruritus Numerical Rating Scale [WP-NRS] score of 0/1 [no/minimal itch]). We evaluated long-term maintenance of optimal treatment targets with upadacitinib, an oral selective JAK inhibitor approved for moderate-to-severe AD in adolescents and adults. Methods: This 140-week interim analysis included adolescents and adults with moderate-to-severe AD who were randomized at baseline to upadacitinib 15 mg (UPA15) or 30 mg (UPA30) in the ongoing, phase 3, double-blind Measure Up 1 and 2 studies. Assessments included the proportion of patients (at the population level) who maintained EASI 90, WP-NRS 0/1, or simultaneous achievement of EASI 90 + WP-NRS 0/1 responses from week 16 (end of the placebo-controlled period) onwards. Data are reported as observed cases with no imputation for missing data. Results: Among patients who achieved EASI 90 at week 16 (UPA15, n=298; UPA30, n=384), EASI 90 was maintained by 79.8% (UPA15) and 83.7% (UPA30) at week 52, 76.7% (UPA15) and 83.0% (UPA30) at week 100, and 74.0% (UPA15) and 84.2% (UPA30) at week 140. Of patients achieving WP-NRS 0/1 at week 16 (UPA15, n=193; UPA30, n=281), WP-NRS 0/1 was maintained by 69.4% (UPA15) and 72.0% (UPA30) at week 52, 65.6% (UPA15) and 68.4% (UPA30) at week 100, and 62.3% (UPA15) and 66.0% (UPA30) at week 140. Of patients simultaneously achieving EASI 90 + WP-NRS 0/1 at week 16 (UPA15, n=156; UPA30, n=243), maintenance was achieved by 68.1% (UPA15) and 70.8% (UPA30) at week 52, 62.7% (UPA15) and 66.5% (UPA30) at week 100, and 58.7% (UPA15) and 64.4% (UPA30) at week 140. Among patients who did not maintain optimal outcomes, most still achieved clinically meaningful responses. Conclusion: Most patients maintained optimal skin and itch outcomes through 140 weeks of upadacitinib treatment, demonstrating its potential to provide sustained long-term disease control in atopic dermatitis.

The Promotion of Non-Communicable Disease Screening in Gurage Zone, Ethiopia: A Mixed-Method Study

Background: Despite the high non-communicable disease (NCD) mortality in Ethiopia, NCD screening in the country remains suboptimal. This study assessed the health communication process and materials designed to promote NCD screening among adult primary healthcare facility attendants in the Gurage Zone, Ethiopia. Methods: A parallel mixed-methods approach was employed. Seven health communication materials were evaluated using the Modified Clear Communication Index Score by the Center for Disease Control and Prevention (CDC). Seven key informants who were involved in the production were interviewed to explore the process. Users’ satisfaction with the materials was assessed through a cross-sectional survey (N = 412). We used multivariable logistic regression with SPSS version 27 software to determine the factors associated with users’ satisfaction. Thematic analysis was applied for the qualitative data analysis using Opencode 4.03 software. Results: Qualitative interviews indicated that the production process relied on evidence, involved stakeholders, and included pretesting. The CDC index score revealed that five of the seven materials were considered clear and user-friendly, whereas two required improvement. Overall users’ satisfaction with the material was high with a mean score of 22.10 (SD ± 2.34; min: 14, max: 25). Age and educational status had significant positive association with users’ satisfaction. Conclusions: Developing health communication materials on promoting NCD screening based on evidence, stakeholders’ input, and pretesting can lead to good quality material and user satisfaction. We recommend future research works to measure changes in NCD screening service uptake as a result of using the health communication materials considered in this study.

Abstract C028: Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence

Abstract There have been improvements in clinical risk stratifications for oral cavity squamous cell carcinoma (OSCC) with the AJCC 8th edition staging system. Other studies suggest the addition of a metric of specific immune interactions in and around the tumor may be helpful to further stratify patients, with mixed findings. The advent of spatial imaging has allowed a global view for assessing tumor features in the context of all surrounding cell interactions. We hypothesize that the lack of architectural information could contribute to varied clinical outcomes in previous studies, such as tumor recurrence. This highlights how spatial technologies could aid in understanding the role of tissue architecture and its influence on biology and medicine. To study tissue remodeling spatially, we focused on multiplexed-ion beam imaging (MIBI), a spatial proteomics platform to visualize 40 immuno-onco proteins simultaneously. Our banked patient cohort consists of 20 recurrent and 49 non-recurrent OSCC primary surgery samples. Clinical metadata capturing pathologic stage, alcohol use, smoking history, survival data, and more were also collected. With our pathologist, we curated 290 field-of-views (FOVs) of matched primary tumors, uninvolved lymph nodes, and metastatic lymph nodes (if any). Downstream computational analysis using existing MIBI codebases augmented with in-house spatial analytics has revealed a robust spatial dataset. After using machine-learning algorithms to cell segment our images, we validated these assigned cells and marker staining to further annotate cell populations. When we analyzed direct cell interactions, there was a decrease in heterogeneity in immune interactions within recurrent patients compared to non-recurrent patients. To ascertain how the loss of these interactions affected recurrence prognosis, we investigated their prevalence within the tumor border vicinity. We hypothesize that the proximity and cell-cell interactions near the border will promote a tumor-suppressive environment. Utilizing centroid-to-centroid distance measurements, we distilled the top 30 cell-cell interactions within a 100-micron distance from the tumor border. Cell pairs involving macrophage tissue-resident memory cells and CD8 T memory resident cells were more abundant in recurrent patients, while pairs involving CD4 T regulatory and CD8 cells were found in non-recurrent patients. Reassuringly, cell pairings involving myeloid cells were upregulated in the recurrent cohort as expected. Interestingly, cancer-associated fibroblast cell pairings were upregulated indiscriminately in both patient sub- cohorts. This suggests that the impact of certain known immunosuppressive changes may contribute in varying amounts to disease control. Our data demonstrates differences in the architecture of tumors with known divergent outcomes, which suggests global tissue-level changes could be a predictive factor. Clinically, interrogating these interactions of interest could guide treatment escalation or de-escalation in the future. Citation Format: Connie J. Zhou, Jane Lee, Rebecca Jaszczak, Steven R. Long, Patrick K. Ha, Matthew H. Spitzer. Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C028.

Orbital metastases from breast cancer: three case reports

Purpose: to describe rare cases of orbital metastases from breast cancer.Material and Methods. Three cases of Luminal A(1) and B(2) breast cancer with orbital metastases were identified and studied during the period from 01.01.2018 to 01.05.2024. Metastasis to the orbit was detected 5, 2 and 1.5 years after radical mastectomy for breast cancer. Patients received chemotherapy and radiation therapy.Results. Cases of orbital metastasis originating from breast cancer were found to have a low frequency, but may be associated with a long period between cancer diagnosis and initiation of treatment. Early detection of breast cancer and its active treatment with chemotherapy and radiation therapy are important factors in preventing orbital metastasis.Conclusion. A routine follow-up surveillance after radical treatment of breast cancer is important because there is an increase risk of developing orbital metastasis. Comprehensive strategies for treating breast cancer metastases can provide long-term disease control.

ATUAÇÃO DO FARMACÊUTICO NA ATENÇÃO PRIMÁRIA A SAÚDE

Primary health care is essential in the organization of health systems, functioning as the gateway to health services and the main point of contact between users and the system. Within this context, the pharmacist plays a primary and active role in promoting health and preventing diseases, offering guidance on the correct use of medications, preventing problems associated with them and promoting healthy habits. This involvement occurs both at the individual level, through personalized counseling for patients, and at the community level, through educational and health awareness initiatives. In this way, the pharmacist demonstrates his versatility as a health agent, adapting to the specific needs of each population served in primary care. Investigate the importance of the pharmacist’s role in primary health care and its impacts on health promotion and disease prevention. Exploratory and comparative bibliographic review based on qualitative research. Investments in continuing education, development of policies and guidelines that promote their integration into the health team and strengthening interprofessional collaboration were recommended. It was concluded that the role of the pharmacist in primary health care is essential for promoting the health of the population and strengthening the health system as a whole. Its comprehensive and multifaceted role demands recognition, appreciation and continuous investment to ensure that it can continue to play its role efficiently, benefiting a healthier and more resilient society.

Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

Discussion on the treatment of diabetic kidney disease based on the "gut-fat-kidney" axis.

Diabetic kidney disease is the main cause of end-stage renal disease, and its prevention and treatment are still a major clinical problem. The human intestine has a complex flora of hundreds of millions of microorganisms, and intestinal microorganisms, and their derivatives are closely related to renal inflammatory response, immune response, and material metabolism. Brown adipose tissue is the main part of adaptive thermogenesis. Recent studies have shown that activating brown fat by regulating intestinal flora has good curative effects in diabetic kidney disease-related diseases. As an emerging medical concept, the "gut-fat-kidney" axis has received increasing attention in diabetic kidney disease and related diseases. However, the specific mechanism involved needs further study. A new theoretical basis for the prevention and treatment of diabetic kidney disease is presented in this article, based on the "gut-fat-kidney" axis.