Chronic Disease Research Articles

Imaging of ventilation and lung injury with low-frequency tomographic ultrasound.

Mechanical ventilation in the intensive care unit (ICU) is a life-saving technique for patients with acute respiratory failure, but is also associated with a high incidence of complications in the injured lung. Currently, there is no widely used monitoring technique to guide the ventilator setting to facilitate a precision medicine approach or to provide a real-time alert for developing adverse pulmonary conditions. Conventional ultrasound has been used as a thoracic bedside technology, but the lack of signal penetration into lung tissue results in images that often contain more information in their artifacts than in the images themselves. Perhaps the greatest obstacle to using traditional ultrasound in the ICU is the need for highly skilled technicians to perform the data collection. In contrast, low-frequency ultrasound (50-500 kHz) has been shown to penetrate the lung, and can detect air trapping in patients with chronic obstructive pulmonary disease (COPD). Here, we present a method of collecting low-frequency ultrasound computed tomographic (USCT) data in vivo on a mechanically ventilated porcine model and computing tomographic reconstructions of airflow during tidal breathing and induced lung injuries. We evaluate the ability of the novel low-frequency USCT system to image regional changes in sound speed in the thorax due to changes in airflow during tidal breathing and induced lung injuries. This represents the first study of low-frequency tomographic ultrasound imaging in vivo and the first to produce tomographic images of ventilatory changes invivo. USCT and computed tomography (CT) scan data were collected alternately on a mechanically ventilated Landrace pig weighing approximately 75 kg during tidal breathing, induced pneumothorax, atelectasis, and pleural effusion. The pneumothorax was induced by injecting air through a 5 mm thick intrathoracic tube inserted in the 8th posterior intercostal space. After removing the air, atelectasis was induced by ventilating the animal with a high concentration of oxygen and low tidal volumes. The pleural effusion was induced by injecting a saline solution through the tube. The USCT data were collected at 125 kHz using the USCT low-frequency ultrasound tomography (LUFT) system on a transducer belt placed around the animal's thorax. Tomographic reconstructions were computed from the USCT data using a regularized refraction-corrected Gauss-Newton-based time-of-flight reconstructionalgorithm. Cyclic changes in computed lung area during tidal breathing were demonstrated to agree with the respiratory rate on the mechanical ventilator. Reconstructed images computed at time steps during the procedure demonstrate regional changes consistent with what would be expected during the induced lung injury. No ground truth was available for images during the procedures since CT scans could only be taken before and after each established lunginjury. In this work, we have demonstrated in the first in vivo study using a mechanically ventilated porcine animal model that low-frequency ultrasound tomography has the ability to image regional changes in sound speed in the thorax corresponding to changes in airflow during tidal breathing and induced lung injury. The results show promise for using low-frequency USCT as a bedside imaging technique in the future for patients with acute respiratory distresssyndrome.

Validation of Systemic Complement Signatures in the Progression of Chronic Obstructive Pulmonary Disease

Validation of Systemic Complement Signatures in the Progression of Chronic Obstructive Pulmonary Disease

Use of alternative therapies in pain management in domestic animals: A narrative review of the literature

Objective: To explore the impact of alternative therapeutic approaches on pain management and animal welfare, highlighting the integration of complementary methods into conventional treatments. Animal welfare is directly related to quality of life, which includes psychological, physical, environmental and social factors. Given the many facets of pain and the individual responses of animals to it, it is difficult to assess this complex and subjective experience. To address pain, it is essential to observe physiological and behavioral signs. To do this, tools such as the University of Melbourne Pain Scale can be used to assess pain intensity. Traditional methods are being supplemented by new alternative therapies such as acupuncture, homeopathy, herbal medicine and aromatherapy. While acupuncture stimulates specific points to restore balance, Bach flower remedies offer a more comprehensive approach that focuses on emotions. With caution, aromatherapy can alleviate anxiety and stress. Although cannabidiol (CBD) has the potential to treat chronic diseases and relieve pain, further research is needed to confirm its safety and efficacy. These alternative therapies offer valuable options for managing pain and improving animal welfare, encouraging continued research and personalized treatments.

Comparison of the clinical efficacy of dienogest and drospirone/ethinyl estradiol in the treatment of ovarian endometriosis cysts

Background: Ovarian endometriosis cysts (OEC) are common chronic diseases occurring in women of reproductive age. Hormone therapy, including the use of oral contraceptives (COCs) and progestins, is widely employed in the treatment of endometriosis and OEC. Objective: This study aims to compare therapeutic effects of long-term daily use of dienogest (DNG, 2 mg) versus drospirenone (DRSP, 3 mg)/ethinyl estradiol (EE, 20 μg) daily on ovarian endometrial cysts, particularly focusing on cysts suppression. Methods: A retrospective analysis was conducted on 84 patients diagnosed with OEC, with 42 receiving DNG and 42 treated with DRSP/EE. After 6 months, assessments were made regarding pain symptoms, size of OEC, tumor markers, and adverse reactions. Results: After 6 months of treatment, both DNG and DRSP/EE effectively alleviated pain in patients with ovarian endometriotic cysts. DNG demonstrated more significant improvements than DRSP/EE in reducing tumor size, mainly in terms of higher drug efficacy and greater percentage of tumor shrinkage. However, DRSP/EE significantly reduced the expression of the tumor markers CA125 and CA199 in our study. Patients taking DNG had a higher likelihood of experiencing side effects than those on DRSP/EE, mainly vaginal bleeding and irregular menstrual periods. Conclusions: Both DNG and DRSP/EE are effective in treating ovarian endometrial cysts. DNG appears to be superior in terms of tumor reduction, while DRSP/EE more significantly decreases the expression of the tumor markers and has fewer side effects.

Fibromyalgia progression and association with other diseases and inheritance with management practices in humans

Fibromyalgia is a widespread pain disorder characterized by chronic, diffuse pain, about 1 to 5% around world. While more prevalent in women and adults, it can also manifest in children and adolescents. The specific pathophysiology of fibromyalgia remains unclear, but it is associated with neuronal over sensitization, reduced conditioned pain modulation, cognitive dysfunction, memory loss, and impaired information processing. It has now been categorized as a somatic symptom disorder. This study aimed to investigate fibromyalgia, focusing on its potential hereditary connections and management practices. A key pathophysiological aspect of fibromyalgia is central sensitization, marked by increased functional connectivity with pre-receptive brain areas, decreased connectivity with antinociceptive areas, and alterations in central nervous system neurotransmitters, also in size and shape of specific brain areas. Fibromyalgia is not directly inherited from parents to offspring, it does exhibit a tendency to cluster within families. The serotonin transporter gene, characterized by single nucleotide polymorphism with "S" (short) allele, is more prevalent in individuals with fibromyalgia and psychological distress. In conclusion, fibromyalgia is a widespread pain disorder with a substantial impact on the central nervous system, resulting in significant disability and an elevated risk of chronic diseases. Early diagnosis and intervention can minimize the impact of fibromyalgia. Physical therapy and non-drug therapies should be customized for each patient. The FDA has approved three drugs including pregabalin, duloxetine, and milnacipran for fibromyalgia treatment.

The Effect of Opioids and Benzodiazepines on Exacerbation Rate and Overall Survival in Patients with Chronic Obstructive Pulmonary Disease on Long-Term Non-Invasive Ventilation.

Background: There is a growing concern that opioids and benzodiazepines can depress the respiratory drive and could contribute to worsening respiratory failure and higher exacerbation frequency in COPD. However, the relationship between the exacerbation rate and medication taken is poorly understood in patients with chronic respiratory failure due to COPD. Methods: As part of a service evaluation project, we analysed 339 patients with COPD who were established on long-term non-invasive ventilation (LT-NIV) at our tertiary centre. We investigated the relationship between benzodiazepine and opioid prescription and clinical outcomes as well as their impact on the exacerbation rate and overall survival following setup. Results: Before LT-NIV setup, 40 patients took benzodiazepines and 99 patients took opioids. Neither benzodiazepine nor opioid use was associated with changes in daytime blood gases, overnight hypoxia or annual exacerbations before NIV setup, but patients taking opioids were more breathless as assessed by modified Medical Research Council scores (3.91 ± 0.38 vs. 3.65 ± 0.73, p < 0.01). Long-term NIV significantly reduced the number of yearly exacerbations (from 3.0/2.0-5.0/ to 2.8/0.71-4.57/, p < 0.01) in the whole cohort, but the effect was limited in those who took benzodiazepines (from 3.0/2.0-7.0/ to 3.5/1.2-5.5/) or opioids (3.0/2.0-6.0/ to 3.0/0.8-5.5/). Benzodiazepine use was associated with reduced exacerbation-free survival and overall survival (both p < 0.05). However, after adjustment with relevant covariates, the relationship with exacerbation-free survival became insignificant (p = 0.12). Opioids were not associated with adverse outcomes. Conclusions: Benzodiazepines and opiates are commonly taken in this cohort. Whilst they do not seem to contribute to impaired gas exchange pre-setup, they, especially benzodiazepines, may limit the benefits of LT-NIV.

Dynamics of inflammatory markers in patients with normal and impaired glucose metabolism during lung exacerbation treatment

Cystic fibrosis (CF) is one of the most common autosomal-recessive inherited diseases. The primary genetic defect in CF is aligned CFTR gene mutation which encodes a membrane protein functioning as cAMP-depended chloride channel. Classic phenotypical manifestations of CF include chronic obstructive pulmonary disease with bronchiectasis, persisting infection (St. aureus, Ps. aeruginosa, B. cepacia) and aberrant inflammatory response, as well as exocrine pancreatic insufficiency with malabsorption, hypotrophy and growth retardation. CFTR deficiency is also accompanied by β-cell pancreatic dysfunction, causing glucose metabolism disturbances and CF-related diabetes. The aim of the study was the comparison of inflammatory markers dynamics in patients with normal and disturbed glucose metabolism during pulmonary exacerbation treatment. The study included 10 patients with impaired glucose tolerance (Group 1) and 24 patients with normal carbohydrate metabolism (Group 2). Patients of the two groups did not significantly differ in demographic characteristics, pulmonary function test and body mass index parameters, as well as in the number of F508del mutation carriers and in the number of those who were infected with Ps. aeruginosa and B. cepacia complex. Blood sampling was performed twice: before and after a routine course of antibiotic therapy. Plasma levels of biomarkers including the antibodies to single- and double-stranded DNA (ss-DNA-IgG, ds-DNA-IgG, respectively), the hormones (dehydroepiandrosterone (DHEA) and DHEA sulfate), C-reactive protein (CRP), Mn-dependent superoxide dismutase (Mn-SOD), and the cytokines (tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), IFNα, tissue growth factor-β1 (TGF-β1), interleukin-4 (IL-4), IL-6, IL-10, IL-17A) were assessed using commercial immunoassay kits. Our study shows that antibiotic treatment did not have a sufficient influence on levels of inflammatory markers in patients with disturbances of glucose metabolism while patients with normal glucose tolerance demonstrated a significant reduction in inflammatory marker values after the therapy. The data may suggest both impaired effectivity of antibiotic treatment and aberrant inflammatory response in patients with glucose intolerance.

Single-Atom Ce-N-C Nanozyme Ameliorates Type 2 Diabetes Mellitus by Improving Glucose Metabolism Disorders and Reducing Oxidative Stress.

Type 2 diabetes mellitus (T2DM) as a chronic metabolic disease has become a global public health problem. Insulin resistance (IR) is the main pathogenesis of T2DM. Oxidative stress refers to an imbalance between free radical production and the antioxidant system, causing insulin resistance and contributing to the development of T2DM via several molecular mechanisms. Besides, the reduction in hepatic glycogen synthesis also leads to a decrease in peripheral insulin sensitivity. Thus, reducing oxidative stress and promoting glycogen synthesis are both targets for improving insulin resistance and treating T2DM. The current study aims to investigate the pharmacological effects of single-atom Ce-N-C nanozyme (SACe-N-C) on the improvement of insulin resistance and to elucidate its underlying mechanisms using HFD/STZ-induced C57BL/6J mice and insulin-resistant HepG2 cells. The results indicate that SACe-N-C significantly improves hepatic glycogen synthesis and reduces oxidative stress, as well as pancreatic and liver injury. Specifically, compared to the T2DM model group, fasting blood glucose decreased by 29%, hepatic glycogen synthesis increased by 17.13%, and insulin secretion increased by 18.87%. The sod and GPx in the liver increased by 17.80% and 25.28%, respectively. In terms of mechanism, SACe-N-C modulated glycogen synthesis through the PI3K/AKT/GSK3β signaling pathway and activated the Keap1/Nrf2 pathway to alleviate oxidative stress. Collectively, this study suggests that SACe-N-C has the potential to treat T2DM.

Anti-Inflammatory and Anticancer Effects of Anthocyanins in In Vitro and In Vivo Studies

Anthocyanins, a class of flavonoid compounds responsible for the vibrant colors of many fruits and vegetables, have received considerable attention in recent years due to their potential health benefits. This review, focusing on evidence from both in vitro and in vivo studies, provides a comprehensive overview of the current state of knowledge regarding the health-promoting properties of anthocyanins. The chemical structure and diversity of anthocyanins, their bioavailability, and their mechanisms of action at the cellular and molecular level are examined. Research on the antioxidant, anti-inflammatory, anticancer, and neuroprotective effects of anthocyanins is critically reviewed. Special emphasis is placed on the role of anthocyanins in the prevention and treatment of chronic diseases such as cardiovascular diseases, diabetes, and neurodegenerative diseases. This review also discusses the challenges of translating in vitro findings to in vivo and highlights the importance of considering dose, bioavailability, and metabolism when assessing the therapeutic potential of anthocyanins. This review concludes with the identification of gaps in current research and suggestions for future directions for anthocyanin studies, including the need for more long-term clinical trials and investigations into potential synergistic effects with other phytochemicals. This comprehensive analysis highlights the promising role of anthocyanins in promoting human health and provides valuable insights for researchers, health professionals, and the nutraceutical industry. This study provides new insights, as it comprehensively investigates the dual anti-inflammatory and anticancer effects of anthocyanins in both in vitro and in vivo models. By uncovering the biological properties of anthocyanins from a variety of natural sources, this research not only expands our knowledge of the action of these compounds at the cellular level, but also enhances their clinical relevance through in vivo validation. Furthermore, the innovative use of anthocyanins may lead to important advances in their therapeutic application in the future.

Relationship between Physical Activity Levels, Quality of Life, and Sociodemographic Attributes among Adults in Tabuk, Saudi Arabia: A Direction toward Sustainable Health

Physical activity (PA) improves quality of life (QOL), yet the relationship between PA, QOL, and sociodemographic factors in Saudi Arabia remains underexplored. This study examined this relationship among 369 adults from Tabuk City, Saudi Arabia. The questionnaire measured PA levels and QOL using the Arabic versions of the International Physical Activity Questionnaire and the 36-item Short-Form Health Survey (SF-36), respectively. Data analyses included chi-square, Mann–Whitney U, and Kruskal–Wallis H tests alongside a multivariate regression analysis. Among the SF-36 scores, marital status (p = 0.005), history of chronic diseases (p = 0.004), and medication use (p = 0.001) showed significant differences; pain (80.6 ± 21.5) and energy/fatigue (63.0 ± 18.5) scored highest and lowest, respectively; and sex was significantly associated with PA levels (p = 0.001). The average total SF-36 score was 69.5 ± 15.7, and 42.5% of participants reported low PA. Participants with moderate PA had significantly higher SF-36 scores (p = 0.003), energy/fatigue (p &lt; 0.0001), emotional wellbeing (p = 0.009), and general health (p = 0.004) scores compared with those with low PA. The significant association between PA and QOL underscores the need for sustainable health programs to enhance and maintain PA in alignment with the Saudi Vision 2030 QOL program. It can also inform the development of targeted interventions to enhance PA levels and improve QOL aspects within communities, considering specific sociodemographic attributes to ensure effectiveness and inclusivity.

Preclinical Evaluation of Electronic Health Records (EHRs) to Predict Poor Control of Chronic Respiratory Diseases in Primary Care: A Novel Approach to Focus Our Efforts.

Background/Objectives: Managing chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) within the Spanish Sistema Nacional de Salud (SNS) presents significant challenges, particularly due to their high prevalence and poor disease control rates-approximately 45.1% for asthma and 63.2% for COPD. This study aims to develop a novel predictive model using electronic health records (EHRs) to estimate the likelihood of poor disease control in these patients, thereby enabling more efficient management in primary care settings. Methods: The Seleida project employed a bioinformatics approach to identify significant clinical variables from EHR data in primary care centers in Seville and Valencia. Statistically significant variables were incorporated into a logistic regression model to predict poor disease control in patients with asthma and COPD patients. Key variables included the number of short-acting β-agonist (SABA) and short-acting muscarinic antagonist (SAMA) canisters, prednisone courses, and antibiotic courses over the past year. Results: The developed model demonstrated high accuracy, sensitivity, and specificity in predicting poorly controlled disease in both asthma and COPD patients. These findings suggest that the model could serve as a valuable tool for the early identification of at-risk patients, allowing healthcare providers to prioritize and optimize resource allocation in primary care settings. Conclusions: Integrating this predictive model into primary care practice could enhance the proactive management of asthma and COPD, potentially improving patient outcomes and reducing the burden on healthcare systems. Further validation in diverse clinical settings is warranted to confirm the model's efficacy and generalizability.

A 3D Epithelial-Mesenchymal Co-Culture Model of the Airway Wall Using Native Lung Extracellular Matrix.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by ongoing inflammation, impaired tissue repair, and aberrant interplay between airway epithelium and fibroblasts, resulting in an altered extracellular matrix (ECM) composition. The ECM is the three-dimensional (3D) scaffold that provides mechanical support and biochemical signals to cells, now recognized not only as a consequence but as a potential driver of disease progression. To elucidate how the ECM influences pathophysiological changes occurring in COPD, in vitro models are needed that incorporate the ECM. ECM hydrogels are a novel experimental tool for incorporating the ECM in experimental setups. We developed an airway wall model by combining lung-derived ECM hydrogels with a co-culture of primary human fibroblasts and epithelial cells at an air-liquid interface. Collagen IV and a mixture of collagen I, fibronectin, and bovine serum albumin were used as basement membrane-mimicking coatings. The model was initially assembled using porcine lung-derived ECM hydrogels and subsequently with COPD and non-COPD human lung-derived ECM hydrogels. The resulting 3D construct exhibited considerable contraction and supported co-culture, resulting in a differentiated epithelial layer. This multi-component 3D model allows the investigation of remodelling mechanisms, exploring ECM involvement in cellular crosstalk, and holds promise as a model for drug discovery studies exploring ECM involvement in cellular interactions.

Muscle endurance, neuromuscular fatigability, and cognitive control during prolonged dual-task in people with chronic obstructive pulmonary disease: a case–control study

Abstract Purpose Recent studies suggest that, compared to healthy individuals, people with chronic obstructive pulmonary disease (pwCOPD) present a reduced capacity to perform cognitive-motor dual-task (CMDT). However, these studies were focused on short-duration CMDT offering limited insight to prolonged CMDT inducing fatigue, which can be encountered in daily life. The present study aimed to explore the effect of adding a cognitive task during repeated muscle contractions on muscle endurance, neuromuscular fatigability, and cognitive control in pwCOPD compared to healthy participants. Methods Thirteen pwCOPD and thirteen age- and sex-matched healthy participants performed submaximal isometric contractions of the knee extensors until exhaustion in two experimental sessions: (1) without cognitive task and (2) with a concurrent working memory task (i.e., 1-back task). Neuromuscular fatigability (as well as central and peripheral components measured by peripheral magnetic stimulation), cognitive performance, and perceived muscle fatigue were assessed throughout the fatiguing tasks. Results Independently to the experimental condition, pwCOPD exhibited lower muscle endurance compared to healthy participants (p = 0.039), mainly explained by earlier peripheral fatigue and faster attainment of higher perceived muscle fatigue (p &lt; 0.05). However, neither effect of cognitive task (p = 0.223) nor interaction effect (group × condition; p = 0.136) was revealed for muscle endurance. Interestingly, cognitive control was significantly reduced only in pwCOPD at the end of CMDT (p &lt; 0.015), suggesting greater difficulty for patients with dual tasking under fatigue. Conclusion These findings provide novel insights into how and why fatigue develops in COPD in dual-task context, offering a rationale for including such tasks in rehabilitation programs.

Changes in Attitudes towards Influenza and Pneumococcal Vaccination during the Subsiding COVID-19 Pandemic-Results of a Longitudinal Survey Study among Risk Groups in Germany between 2021 and 2023.

In many countries, an increase in influenza and pneumococcal vaccination rates was observed during the COVID-19 pandemic. We examined how attitude, risk perception and knowledge towards influenza and pneumococcal vaccines of at-risk patients developed when the COVID-19 pandemic subsided and if COVID-19 vaccination attitude (VA) was still associated with the attitudes towards the two other vaccines. We used longitudinal data from two surveys conducted in Germany in 2021 and 2023 among persons with chronic diseases. We assessed VA, risk perception, vaccination knowledge and further psychological determinants of vaccine acceptance. Structural equation modelling using full information maximum likelihood was used to estimate multivariate regressions with planned missing data. Among 543 respondents, the influenza and pneumococcal vaccination rates remained relatively stable between 2021 and 2023. VA also remained unchanged at a moderately positive level, while COVID-19 VA decreased. A constantly positive association between COVID-19 VA and influenza as well as pneumococcal VA was found, independent from a general VA. The perceived danger of influenza increased between 2021 and 2023 and was among the strongest predictors of influenza VA. Also at the subsiding pandemic, COVID-19 VA was constantly associated with the influenza and pneumococcal VA. It seems sensible to take these aspects into account when designing future vaccination campaigns for at-risk patients. DRKS00024561. Registered 9 March 2021.

Hepatitis B

Hepatitis B is a viral infection caused by the Hepatitis B virus (HBV), primarily affecting the liver and leading to both acute and chronic disease. With over 250 million individuals suffering from chronic Hepatitis B, it poses a significant global health challenge, being a leading cause of liver cirrhosis, liver failure, and hepatocellular carcinoma. This study aims to elucidate the transmission pathways, treatment options, and necessary public health strategies for Hepatitis B. We analyze the modes of transmission, which include contact with infectious body fluids—primarily through perinatal transmission, unprotected sexual contact, and sharing contaminated needles. Despite the availability of an effective vaccine since the 1980s, Hepatitis B remains endemic in many parts of Asia and Africa due to limited immunization coverage. The pathogenesis of HBV involves complex interactions between the virus and the host immune system, potentially leading to liver inflammation and fibrosis. Clinical presentations vary widely, ranging from asymptomatic infections to severe liver disease. Current treatment options for chronic Hepatitis B include antiviral medications such as tenofovir and entecavir, which suppress viral replication but do not cure the infection. Recent advancements in therapeutic strategies, including novel antivirals and immune modulators, show promise for more effective management and potential cures in the future. Comprehensive public health strategies—such as vaccination, screening, and education—are crucial for controlling the spread of HBV and reducing the global burden of Hepatitis B-related complications.

Assessing Heatwave-Related Deaths among Older Adults by Diagnosis and Urban/Rural Areas from 1999 to 2020 in Slovenia

Background: The association between mortality and heatwaves is well documented. Heatwaves frequency, intensity, and duration increase with global climate change. The most vulnerable group for dying during heatwaves is older people. Knowing which diseases contribute to a higher number of deaths during heatwaves is important for planning appropriate public health preventive measures. Methods: We assessed the short-term association between the number of deaths for older adults (75+ years) and heatwaves in the years 1999 to 2020 in Slovenia. We estimated the relative risks (RR) with a 95% confidence interval for the number of deaths for the observed diagnosis (all causes, circulatory, respiratory) and urban vs. rural areas associated with heatwaves in Slovenia for each year, comparing the number of deaths during heatwaves with reference days. Results: Most years showed no significant increase in deaths during heatwaves for those aged 75 and older. However, in 2006, 2007, 2014, and 2015, there was a significant increase in deaths during heatwaves. For the general population, heatwaves were associated with an increase in deaths due to all causes: 10% more in 2006 and 26% more in both 2007 and 2014. For those aged 75 and older, heatwaves were associated with an increase in deaths due to all causes: 22% more in 2007, 27% more in 2014, and 28% more in 2015. For those aged 75 and older, heatwaves were associated with an increase in deaths due to circulatory system diseases: 25% more in 2006, 33% more in 2007, 30% more in 2014, and 27% more in 2015. Regarding urban vs. rural areas, in 2006 and 2012, the elderly in urban areas were more affected, with 33% and 26% more deaths, respectively. In contrast, in 2007, 2014, and 2015, old age population in rural areas was more affected, with 29%, 26%, and 31% more deaths, respectively. Conclusions: According to the literature data, older adults are most susceptible to the effects of extreme heat due to physiological changes that occur with aging, chronic diseases, certain medications, a sedentary lifestyle, and social isolation. The results of our study will help in planning appropriate preventive public health measures to better protect older adults during the next heatwaves in Slovenia.

Insulin‐like growth factor‐1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver‐related mortality

SummaryBackground and AimsWe aimed to characterise insulin‐like growth factor‐1 (IGF‐1) signalling in patients with advanced chronic liver disease (ACLD).MethodsConsecutive patients undergoing hepatic venous pressure gradient [HVPG] measurement were prospectively included. Clinical stages were defined as follows: probable ACLD (pACLD): liver stiffness ≥10 kPa and HVPG ≤5 mmHg, S0: mild PH (HVPG 6–9 mmHg), S1: clinically significant PH (CSPH), S2: CSPH with varices, S3: past variceal bleeding, S4: past/current non‐bleeding hepatic decompensation and S5: further decompensation.ResultsIn total, 269 patients were included; 105 were compensated (pACLD: n = 18; S0: n = 30; S1: n = 20; S2: n = 37), and 164 were decompensated (S3: n = 11; S4: n = 89; S5: n = 64). Median levels of IGF‐1 decreased with progressive cirrhosis (from pACLD: 88.5 ng/mL to S5: 51.0 ng/mL; p &lt; 0.001). Patients with CSPH had significantly lower IGF‐1 levels (63.5 ng/mL vs. 81.0 ng/mL; p = 0.001). IGF‐1 showed an independent negative association with body mass index (BMI; aB: −1.56; p &lt; 0.001), enhanced liver fibrosis (ELF) test (aB: −8.43; p &lt; 0.001), MELD (aB: −1.13; p = 0.042) and age (per 10 years; aB: −6.87; p &lt; 0.001). IGF‐1 exhibited an excellent AUROC (0.856) for the prediction of liver‐related death at 6 months of follow‐up. Lower IGF‐1 (per 10 ng/mL) was linked to higher risk of (further) decompensation (0.90; 95% CI: 0.83–0.98; p = 0.016), acute‐on‐chronic liver failure (ACLF; asHR: 0.80; 95% CI: 0.68–0.93; p = 0.004) and liver‐related death (asHR: 0.76; 95% CI: 0.63–0.91; p = 0.004).ConclusionDecreased levels of IGF‐1 reflect impaired hepatic function and fibrogenesis in patients with cirrhosis, which seems particularly relevant in obesity since low IGF‐1 was independently linked to high BMI. Lower IGF‐1 in cirrhosis predicts decompensation, ACLF and liver‐related death.

Effect of IL-7 and IL-7R blockade on cytokine production by peripheral blood t cells from patients with psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory joint disease, often associated with psoriasis. Interactions between immune cells, mainly T lymphocytes, and cells of the osteoarticular system are central in the pathogenesis of PsA. Th1, Th17 cytokines associated with the development of PsA contribute to an increase in the production of cytokines, chemokines, matrix metalloproteinases, adhesion molecules by immune cells, chondrocytes, fibroblasts, and induction of osteoclasts. That leads to the destruction of cartilage and bone tissue. Among the cytokines potentially involved in the pathogenesis of PsA, IL-7 is of particular interest. IL-7 is a T cell survival factor. However, it can promote the production of IFNγ and TNFα by T cells. IL-7 may indirectly promote osteoclast maturation and cartilage degradation. The aim was to investigate the effect of IL-7 and blockade of the α-chain of the IL-7 receptor (IL-7R) in vitro on the production of IL-5, IL-13, IL-2, IL-6, IL-9 IL-10, IFNγ, TNFα, IL-17A, IL-17F, IL-4, and IL-22 by T cells in norm and PsA.The study included 14 patients with PsA in the acute stage of the disease and 8 healthy individuals. To determine cytokines concentration, multiplex analysis was performed using flow cytometry.It was shown that IL-7 enhances the production of Th1, Th2, Th17, Th22, and Th9 cytokines in both patients with PsA and healthy individuals. The exception was IL-2 for both groups. Under the blockade of IL-7R with monoclonal antibodies, the level of IL-6 increases and production of IFNγ, TNFα, IL-17F, IL-10, IL-5, and IL-9 by donors’ cells and production of IFNγ, TNFα, IL-22, IL-2, IL-4, IL-5, IL-13, and IL-9 by cells from patients with PsA decreases relative to production of cells stimulated with IL-7. In donors, the blockade contributed to a change in the balance of Th1/Th2 cytokines: level of IL-4, IL-13 did not change on the background of a decrease in production of IFNγ, TNFα. In patients with PsA, under blockade of IL-7R the production of IL-10 remained at an increased level and concentration of IFNγ, TNFα and IL-2, which are actively involved in the tissue damage mechanisms, decreased. The obtained data indicate the prospect of using the IL-7R as a target for the treatment of psoriatic diseases.

Association of crown-root ratio and tooth survival in Chinese patients with advanced periodontitis: An 11-year retrospective cohort study

IntroductionPeriodontitis is a chronic multifactorial inflammatory disease which eventually lead to tooth loss (TL). Therefore, a retrospective study was conducted to evaluate the status of tooth survival within 11 years after non-surgical periodontal treatment (NSPT) and to analyze the risk factors especially crown-root ratio (CRR) that affected TL in Chinese with advanced periodontitis. Methods3481 teeth of 131 subjects who underwent NSPT were examined retrospectively within a mean follow-up period of 11.6 years. The association of risk factors including clinical and radiographic parameters with TL was assessed using univariate and multivariate Cox regression analyses. Smooth curve fitting and segmented regression model were conducted to show the nonlinear relationship and the threshold effect between CRR and the risk of TL. Results347 teeth were lost in 97 patients in this study. Male, diabetes mellitus, heavy-smoker, molar, probing depth (PD), attachment loss (AL), bleeding on probing (BOP), tooth mobility, and radiographic bone loss were significantly associated with tooth loss (P < 0.05). A nonlinear relationship between CRR and the risk of TL was found, with different turning point values between molars and non-molars (1.9 vs. 2.76). ConclusionsThe findings based on practice-based clinical and radiographic data do suggest a nonlinear relationship between CRR and the survival of teeth, and provide evidence to help clinicians to determine the prognosis of teeth for patients with advanced periodontitis. Clinical SignificanceBased on clinical and radiographic data, this study provides an individualized basis for clinicians to judge the dental prognosis of patients with advanced periodontitis according to the different tooth sites.

Abstract A145: Race and sex disparities in lung cancer screening and evaluation of alternative identifiers in patients’ electronic medical record to better identify lung cancer screening candidates

Abstract Introduction: The US Preventive Services Task Force (USPSTF) recommends lung cancer screening with a low dose CT scan in patients who are 50 – 80 years old with at least a 20 pack-year smoking history and currently smoke or quit in the last 15 years. Yet, only 5.8 percent of eligible Americans were screened in 2022. We investigated demographic screening patterns and evaluated for alternative identifiers in patients’ electronic medical record (EMR) to identify lung cancer screening candidates at a large and diverse cancer center in Los Angeles. Methods: We examined 607 patients with non-small cell lung cancer (NSCLC) treated at the University of Southern California Norris Comprehensive Care Center or Los Angeles General Medical Center from 2009-2023. EMR data included age of diagnosis, sex, race/ethnicity, smoking history, and stage at diagnosis; for patients with unknown number of pack years (n=25) they counted as not qualified for screening. Identifiers investigated were International Classification of Disease, Tenth Revision (ICD-10) code for chronic obstructive pulmonary disease (COPD), prescription of inhaled steroids, and documented lung cancer history. Fisher’s exact test was used to compare proportion of qualified screeners among groups. Results: 35% (215/607) of patients would have qualified for lung cancer screening according to the USPSTF guidelines, including a greater proportion of males 52% (164/313) versus females 17% (51/293) (p&amp;lt;0.0001). In males, Non-Hispanic Whites (NHW) 59% (55/93) had a greater proportion that would qualify compared to Hispanics 41% (31/75) (p=0.0295). In females, NHW 34% (30/89) had the highest proportion of qualifiers while Asians 6% (6/104) and Hispanics 9% (6/66) had the lowest proportion of qualifiers (p&amp;lt;0.0001). 65% (215/332) of smokers qualified for screening; males had a higher percentage who qualified for screening versus females (164/234, 70% vs. 51/98, 52%, p=0.0024). By race, NHW male smokers had the highest proportion of qualifiers 77% (55/71) while Hispanic women had the lowest proportion of qualifiers 50% (6/12). 27% (89/332) of patients were found to have an ICD-10 code for COPD, including 18% (21/117) had an ICD-10 code for COPD who did not qualify. 19% (63/332) smokers received a prescription for inhaled steroids, including 15% (18/117) of them who didn’t qualify for screening. 12% had a family history of lung cancer (39/332), while 9% (10/117) of these patients didn’t qualify for screening. Conclusion: There were significant race and sex screening disparities among known NSCLC patients including under 10% of Asian and Hispanic females. There were about 10-15% known lung cancer patients who would not have qualified for screening found to have an ICD-10 code for COPD, an inhaled steroids prescription, or documented family history. These alternative identifiers may serve as identifiers for lung cancer screening candidates in the EMR to help address race and sex disparities in screening. Future directions should include simulation of these identifiers in larger patient datasets. Citation Format: Darin Poei, Aubree Mades, Iris Yao, Nick Ahn, Ajay Prasad, Jennifer Tsui, Jacob S Thomas, Jorge J Nieva, Robert Hsu. Race and sex disparities in lung cancer screening and evaluation of alternative identifiers in patients’ electronic medical record to better identify lung cancer screening candidates [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A145.