Chronic Disease Research Articles

FAP-catalyzed in situ self-assembly of magnetic resonance imaging probe for early and precise staging of liver fibrosis

Liver fibrosis is an inevitable stage in the progression of most chronic liver diseases. Early diagnosis and treatment of liver fibrosis are crucial for effectively managing chronic liver conditions. However, there lacks a noninvasive and sensitive imaging method capable of early assessing fibrosis activity. Here, we report a molecular magnetic resonance imaging (MRI) probe for imaging fibroblast activation protein (FAP), which is overexpressed on activated hepatic stellate cells (HSCs) even in very early fibrotic livers. This method relies on FAP-catalyzed in situ self-assembly of its substrate probe that leads to the increase of the rotational correlation time (τ R ) of probe, thereby notably amplifies T 1 MRI signal. Thanks to the superior specificity and efficiency of enzymatic reaction, our method has been validated as highly selective and sensitive to FAP in two liver fibrosis mouse models. By establishing a direct correlation between MRI signals and fibrosis activity, our method enables continuous monitoring of liver fibrotic disease progression and assessment of treatment responses.

Comorbidity-related risk factors for acute respiratory distress syndrome in sepsis patients: A systematic review and meta-analysis.

Acute respiratory distress syndrome (ARDS) presents a significant challenge in the management of sepsis, with various comorbidities potentially influencing its development. Understanding the impact of these comorbidities is crucial for improving patient outcomes. This meta-analysis was conducted to investigate the relationship between various comorbidities and the development of ARDS in patients with sepsis, with the aim of improving understanding and management of this condition. The study included adult sepsis patients from 8 studies, totaling 16,964 participants. Risk of bias was assessed using the Newcastle-Ottawa scale (NOS), and the data analysis was performed and reported as pooled odds ratios (ORs) computed using a random-effects model. Heterogeneity and publication bias were assessed using the I2 statistic and Doi plots with the Luis Furuya-Kanamori (LFK) index, respectively. Chronic obstructive pulmonary disease was significantly associated with an increased risk of ARDS (OR: 1.43, 95% confidence interval (95% CI): 1.02-2.01). Other comorbidities showed no significant associations: diabetes mellitus (DM) (OR: 0.88, 95% CI: 0.69-1.11), hypertension (HTN) (OR: 0.86, 95% CI: 0.56 to 1.34), coronary artery disease (CAD) (OR: 0.95, 95% CI: 0.86-1.06), congestive heart failure (CHF) (OR: 1.08, 95% CI: 0.61 to 1.90), chronic kidney disease (CKD) (OR: 0.89, 95% CI: 0.65-1.22), chronic liver disease (CLD) (OR: 1.13, 95% CI: 0.61-2.09), and cancer (OR: 0.90, 95% CI: 0.59-1.35). Additional analyses indicated moderate-to-high heterogeneity and some evidence of publication bias. Chronic obstructive pulmonary disease is a notable risk factor for ARDS in sepsis patients, suggesting the need for enhanced surveillance and management in this group. Further research is necessary to understand the mechanisms and explore other potential ARDS risk factors in sepsis.

Homocysteine levels and cardiovascular disease risk factors in chronic kidney disease (CKD), hypertensive and healthy Nigerian adults: a comparative retrospective study

ObjectivesTo investigate homocysteine (Hcy) levels in individuals with chronic kidney disease (CKD), hypertension and a healthy Nigerian population, and to assess their association with cardiovascular disease (CVD) risk.SettingThe study was...

Clinical Manifestations and Prognosis of Chronic Kidney Disease after Hematopoietic Stem Cell Transplantation

Introduction: Kidney disease is a common complication of hematopoietic stem cell transplantation (HSCT). However, there is limited research on the clinical pathology and prognosis of patients who develop chronic kidney disease (CKD) after HSCT. Methods: A retrospective analysis was conducted on 50 patients diagnosed with CKD through kidney biopsy between September 2008 and May 2024. The patients were categorized based on their pathological presentations into groups with thrombotic microangiopathy (TMA) or membranous nephropathy (MN). Results: The renal pathological results revealed that TMA was the most prevalent pathological type, accounting for 40% of cases, followed by MN at 32%, and mesangial proliferative glomerulonephritis (MsPGN) at 16%, among others. Clinically, patients with TMA predominantly presented with renal insufficiency, whereas those with MN mainly exhibited nephrotic syndrome. Patients with MN showed favorable responses to treatment, achieving complete and partial response rates of 14.3% and 71.4%, respectively. Among the 50-patient cohort, 45 remained alive, corresponding to a 5-year overall survival rate of 87.8%. The 5-year renal survival rate was observed to be 78.8%, with 3 patients (6.98%) requiring kidney replacement therapy. Conclusion: TMA and MN are the two most common pathological findings in patients with CKD following HSCT. Both conditions exhibit favorable responses to combined steroids and immunosuppressants therapy. Notably, patients with MN demonstrate a higher overall response rate and superior treatment outcomes compared to those with TMA.

Airborne particulate matter exposure in male sugarcane workers at risk for chronic kidney disease in Guatemala.

There is an international epidemic of chronic kidney disease of unknown cause (CKDu) in agricultural working populations. Particulate air pollution is a likely contributing factor in populations at risk for CKDu, but there is little personal breathing zone data for these workers. We collected 1 to 3 personal breathing zone particulate matter <5 microns (PM5) gravimetric measurements in 143 male sugarcane harvesters over 2 seasons and concurrent ambient samples using personal sampling pumps and cyclone inlets as a sampling train. Due to very high concentrations observed during a pilot of these methods, personal breathing zone sampling duration was set to 4h, beginning either at the start of a work shift (AM) or delayed for 4h (PM). To obtain full-shift exposure concentrations we calculated 8-h time-weighted average (TWA, in µg/m3) estimates of each worker's full-shift personal breathing zone PM5 exposure concentration by averaging their individual monitored concentration with the median concentration of the unmonitored AM or PM segment from all workers that day to obtain an 8-h TWA. Median full-shift personal TWA PM5 concentrations were 449 μg/m3 (range 20.5 to 1,930 μg/m3), which were much higher than ambient concentrations in these fields (median 136, range 22.5 to 2,360 μg/m3). These findings document very high personal breathing zone PM5 exposure in workers at risk for CKDu: median concentrations for all workers were 3.5 (range <1 to 33.6) times as high as concurrent ambient concentrations. These findings suggest that ambient measurements of particulate matter are insufficient to estimate personal exposure in this population and that personal breathing zone monitoring should be used to fully explore air pollution as a risk factor for CKDu. Given that particulate matter from this source likely has multiple hazardous constituents, future research should focus on characterizing all constituents and explore associations with biomarkers of kidney injury.

Patient experience and primary care teams: a cross-sectional survey of French elderly patients

ObjectiveTo assess whether patient experience is better for patients followed in a primary care team (PCT) than for patients with traditional follow-up in usual care.DesignA cross-sectional survey based on a...

Assessing toxicological risk of nanoplastics contaminants in food and feed from ingestion pathway to human diseases

The extensive use of plastic without an effective management system is linked to significant environmental pollution issues. The fragmentation of various types of plastic waste leads to the formation of microplastics (MPs) and nanoplastics (NPs). NPs, measuring less than 0.1 μm pose a latent danger to the human food chain caused by the ability to traverse biological membranes than MPs, potentially leading to various chronic diseases. The widespread distribution of NPs across diverse environmental matrices and their subsequent infiltration into food and feed chains precipitates various emerging health concerns. NPs contaminate food production systems and leach from plastic packaging, infiltrating organisms at various trophic levels. Seafood, processed foods, and drinking water serve as vectors for absorption and accumulation in human tissues. The pervasive contamination pathway poses substantial risks to human health through multiple exposure routes, primarily ingestion. It can lead to cytotoxicity, inflammation, genotoxicity, and apoptosis. This review summarizes the implications of NPs exposure that triggers various diseases such as inflammatory bowel disease (IBD), kidney dysfunction, liver disease, heart problems, brain disorders, reproductive issues, and cancer. Currently, no established method exists to treat NPs that humans may have already ingested. Hence, it is urgent to mitigate the harmful effects of NPs through the development and implementation of innovative, efficient, and sustainable environmental decontamination strategies. This discussion highlights several advanced remediation techniques that can effectively reduce the toxicity of NPs in environmental systems, thus mitigating their associated risks.

Compositional analysis of lymphocytes and their relationship with health outcomes: findings from the health and retirement study

Abstract Background Immunosenescence, the gradual deterioration of the immune system, is critical for aging-related diseases. However, the lack of detailed population-level immune data has limited our understanding, underscoring the need for innovative analytical approaches. The Health and Retirement Study (HRS) in the United States provides a unique opportunity to examine T and B lymphocyte subsets using compositional data analysis and dimension reduction techniques. Methods We constructed a hierarchical tree structure to map relationships among T and B subset cells in HRS. Network analysis examined conditional dependence across 16 immune subset cells, while stepwise redundancy analysis (SRDA) identified a subset of pairwise logratio measures that capture main variance in immune composition. We conducted two sets of supervised learning analyses: first, linear penalized log-contrast models to examine the associations between subset cells and three health outcomes (chronic disease index, self-reported health, and frailty level); second, linear regressions to examine the associations between the top selected logratios and health outcomes. Findings Our study included 6,250 participants from the HRS with a median age of 68. Network analysis showed some dependence among 16 immune subset cells, including associations between central memory CD4 + T cells and both other CD4 + T cells and other lymphocytes, as well as between central memory CD8 + T cells and other CD8 + T cells. SRDA identified nine key log-ratio measures, explaining over 90% of the variance in immune composition. Linear penalized log-contrast models showed that a lower proportion of naïve CD4 + T cells and higher proportions of other CD4 + and central memory CD8 + T cells were significantly associated with greater chronic disease burden, poorer self-reported health, and higher frailty levels. Linear regression models using log-ratios reinforced these patterns, showing that a higher ratio of other lymphocytes over naïve CD4 + T cells and terminally differentiated effector memory CD4 + T cells over other CD8 + T cells were associated with greater chronic disease burden, poorer self-reported health, and higher frailty levels. In contrast, a higher ratio of other lymphocytes over central memory CD4 + T cells was associated with better health outcomes. Interpretation Our findings highlight the value of a systems-based approach and compositional analysis in understanding immunosenescence and its impact on health. The identified subset cells and logratio measures provide meaningful insights into immune aging and warrant further investigation to explore their long-term relationships with health outcomes.

Danshensu Derivatives: A Series of Promising Drugs With Protective Effects Against Cardiocerebrovascular Diseases and Cancers.

Salvia miltiorrhiza (Danshen in Chinese) is a traditional medicinal plant with an extensive range of cardiocerebrovascular protective effects widely used in China and other Asian countries. Danshensu (DSS) is the most important water-soluble component of Danshen and has significant antioxidant, anti-inflammatory, antiplatelet aggregation, antitumor, and other pharmacological activities. However, DSS has poor fat solubility and is unstable due to its o-phenol hydroxyl and α-hydroxy carboxylic acids. Therefore, it is necessary to develop new DSS derivatives through reasonable structural modifications to obtain new drugs with better activity, preferable stability, and higher bioavailability. Our team has previously investigated the effect of Danshen on chronic diseases. Through nearly two decades of research, we have made considerable research progress on the impact of DSS derivatives on cardiocerebrovascular diseases. Based on the published literature and our previous work, it was confirmed that DSS derivatives have a wide range of cardiocerebrovascular protective and other pharmacological effects. Here, this review summarized recent research progress on DSS derivatives in terms of design, synthesis, pharmacological effects, and molecular mechanisms to provide new insights for further research.

Chinese Medicine for the Treatment of Liver Cirrhosis: The Mechanism of Cellular Autophagy.

Liver cirrhosis is a critical stage in the progression of various chronic liver diseases, often leading to severe complications such as ascites, hepatic encephalopathy, and a high mortality rate, and it thus poses a serious threat to patient life. The activation of hepatic stellate cells is a central driver of disease progression. Cellular autophagy, a lysosome-mediated degradation process, plays a key role in maintaining cellular function and dynamic homeostasis. Research has shown that autophagy is closely associated with proteins like LC3, Beclin-1, P62, and mTOR, and is regulated through signaling pathways such as PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and AMPK/mTOR. Additionally, the relationship between autophagy and apoptosis, as well as between autophagy and exosomes, has been further demonstrated. While modern medicine has made progress in treating cirrhosis, it still faces significant limitations. By contrast, numerous studies have demonstrated the efficacy of traditional Chinese medicine in preventing and treating liver cirrhosis by regulating autophagy, with fewer adverse effects. Chinese herbal monomers and formulations can modulate various autophagy-related signaling pathways, including PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, and AMPK/mTOR, and influence key autophagy proteins such as LC3 and Beclin-1. This modulation inhibits hepatic stellate cell activation, reduces extracellular matrix deposition, and exerts anticirrhotic effects. Moreover, Chinese medicine appears to reduce adverse reactions in cirrhosis treatment and lower the risk of disease recurrence. This review explores the mechanisms of autophagy in the prevention and treatment of liver cirrhosis through Chinese medicine, offering new insights for the development of Chinese medicinal therapies for cirrhosis and their rational clinical application.

Structure and function relationships of mucociliary clearance in human and rat airways

Mucociliary clearance is a vital defense mechanism of the human airways, protecting against harmful particles and infections. When this process fails, it contributes to respiratory diseases like chronic obstructive pulmonary disease (COPD) and asthma. While advances in single-cell transcriptomics have revealed the complexity of airway composition, much of what we know about how airway structure impacts clearance relies on animal studies. This limits our ability to create accurate human-based models of airway diseases. Here we show that the airways in female rats and in humans exhibit species-specific differences in the distribution of ciliated and secretory cells as well as in ciliary beat, resulting in significantly higher clearance effectiveness in humans. We further reveal that standard lab-grown cultures exhibit lower clearance effectiveness compared to human airways, and we identify the underlying structural differences. By combining diverse experiments and physics-based modeling, we establish universal benchmarks to assess human airway function, interpret preclinical models, and better understand disease-specific impairments in mucociliary clearance.

Long-Term Safety of Mirikizumab in Patients With Moderately to Severely Active Ulcerative Colitis: An Integrated 2-Year Safety Analysis.

Ulcerative colitis (UC) is a chronic immune-mediated disease requiring ongoing treatment to maintain remission. This report presents the 2-year safety outcomes of mirikizumab, a humanized immunoglobulin G4 anti-interleukin-23p19 monoclonal antibody, in moderately to severely active UC from Phase 3 studies LUCENT-1 (NCT03518086), LUCENT-2 (NCT03524092), and LUCENT-3 (NCT03519945). Patients who underwent induction (LUCENT-1) and maintenance (LUCENT-2), and entered long-term maintenance (LUCENT-3) were assessed in 2 cohorts: induction responders and extended-induction responders. Both cohorts underwent up to 104 weeks of continuous treatment with mirikizumab. Adverse events (AEs) were assessed in these 2 cohorts and within subsets of patients aged ≥60 years and patients using corticosteroids, immunomodulators, or both at baseline. Safety was generally consistent across induction responders (N=333) and extended-induction responders (N=149) and across patient subsets. Nasopharyngitis, COVID-19, arthralgia, UC (worsening/reoccurrence of symptoms), and headache were the most common AEs. Serious AEs were reported in less than 10% of both cohorts. Infections (mostly mild), cerebrocardiovascular events, and malignancies occurred, respectively, in 47.4% and 49.7%, 0.9% and 1.3%, and 0% and 3.4% of induction responders and extended-induction responders. Injection-site reactions (induction responders: 10.2% and extended-induction responders: 8.1%) declined over time. Safety profiles in patient subsets and in the whole population were similar, except for hypertension, which was more frequent in patients aged ≥60 years. The mirikizumab 2-year integrated safety profile in patients with moderately to severely active UC was consistent across subgroups and with previous findings, without new significant safety concerns.

Sirt1-mediated deacetylation in MAFLD: Mechanisms and therapeutic implications

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as a leading cause of chronic liver disease worldwide, with its pathological mechanisms involving multiple factors such as hepatic steatosis, insulin resistance (IR), oxidative stress, and inflammatory responses. In recent years, Sirtuin 1 (SIRT1) has been recognized as a crucial molecular target for improving MAFLD due to its central role in metabolic regulation and cellular homeostasis. This article reviews the mechanisms by which SIRT1 intervenes in the progression of MAFLD: 1) promoting autophagy and enhancing mitochondrial function; 2) regulating lipid metabolism and oxidative stress-related proteins through deacetylation, thereby improving lipid metabolism disorders and reducing ROS accumulation; 3) suppressing inflammatory responses and alleviating liver inflammation damage; 4) ameliorating IR. Preclinical studies have shown that SIRT1 agonists or gene overexpression can significantly improve the histopathological features of MAFLD in animal models. However, the regulation of SIRT1 is tissue-specific and dose-dependent, and its long-term safety and targeted delivery strategies require further exploration. This article systematically summarizes the molecular mechanisms and therapeutic potential of SIRT1 in MAFLD, providing a theoretical basis for developing novel intervention strategies based on SIRT1 regulation.

QUÉ ESTÁ HACIENDO EL MINISTERIO DE SALUD EN TRASPLANTE? ¿QUÉ SUGERIRÍA?

The number of donors and kidney transplants (Tx) in Chile (10 donors per million people (PMP) is compared with the USA and Spain (50 PMP) and Uruguay (20 PMP). Concrete initiatives are proposed to improve this problem. The lack of donors/Tx leads us to a waiting list of 2,000 people, underestimated number, since Tx is not always offered in dialysis centers and patients with advanced Chronic Kidney Disease who will enter dialysis are not considered. Chile has a ministerial level National Coordination Office for Tx, but its operational capacity is limited. The reason is analyzed. To increase the number of effective procurements and the number of Tx, it is proposed: Create a National Tx Organization, with autonomy, budget, executive and oversight capacity. Professionalize the procurement process. Standardize the extraction processes and quality standards. Eliminate the concept of a home kidney, a centralized team of tractors, Evaluate the number and current operation of the Tx centers. Promote the living donor. Promote the cross-matched living donor. Promote the donor with expanded criteria, Follow-up of Tx, the registry as a requirement, and a public registry of the evolution and status of the transplant recipients. Promote the donor with a stopped heart.

Infection by Clonally Related Mycobacterium abscessus Isolates: The Role of Drinking Water.

Mycobacterium abscessus group bacteria (MABS) cause lethal infections in people with chronic lung diseases. Transmission mechanisms remain poorly understood; the detection of dominant circulating clones (DCCs) has suggested potential for person-to-person transmission. This study aimed to determine the role of drinking water in the transmission of MABS. A total of 289 isolates were cultured from respiratory samples (231) and drinking water sources (58) across Queensland, Australia. Whole genome sequences were analysed to identify DCCs and determine relatedness. Half of the isolates (144, 49·8%) clustered with previously described DCCs, of which 30 formed a clade within DCC5. Pangenomic analysis of the water-associated DCC5 clade revealed an enrichment of genes associated with copper resistance. Four instances of plausible epidemiological links were identified between genomically-related clinical and water isolates. We provide evidence that drinking water is a reservoir for MABS and may be a vector in the chain of MABS infection.

Co-creating an Ecology of Design Briefs for people with respiratory disease

ABSTRACT In this study, we introduce a new approach to addressing the complexities of health systems challenges, which we name the Ecology of Design Briefs. This approach offers a structured framework for delivering key leverage points within these challenges and creating a conceptual space for feasible design opportunities. Acknowledging the limited reach of individual design solutions in tackling the complexities of health systems challenges, our approach draws on the ecology concept of Transition Design. The utilisation of the Ecology of Design Briefs results in a collection of interconnected specification documents for design projects that guide the creative process, working together synergistically to tackle the complexities. This approach was applied to enhance hospital care experiences for individuals with acute exacerbations of chronic obstructive pulmonary disease (COPD). Hospitalisations for this group frequently lead to multidimensional negative experiences, and addressing these issues is closely linked to resolving underlying health systems problems. Our findings suggest that the developed briefs provide comprehensive, mutually reinforcing, and detailed insights necessary for understanding these challenges. This study contributes to health systems problem-solving by conceptualising the Ecology of Design Briefs as an approach and documenting its application in a hospital care setting.

Establishing Cross-Specialty Expert Consensus on the Optimal Management of Hyperkalemia in Patients With Heart Failure and Chronic Kidney Disease

Establishing Cross-Specialty Expert Consensus on the Optimal Management of Hyperkalemia in Patients With Heart Failure and Chronic Kidney Disease

Cirrhotic cardiomyopathy: comprehensive insights into pathophysiology, diagnosis, and management.

Cirrhotic cardiomyopathy (CCM) is a cardiac dysfunction linked to chronic liver disease, primarily characterized by impaired cardiac response to stress, despite normal baseline function. It presents with both systolic and diastolic dysfunction, along with electrophysiological changes such as QT interval prolongation. CCM is driven by a combination of systemic inflammation, nitric oxide-induced vasodilation, and neurohormonal dysregulation, leading to myocardial impairment and abnormal vascular responses. Clinically, CCM often remains asymptomatic at rest, but patients may experience exercise intolerance or heart failure during stress. Diagnosis includes echocardiographic evaluation, biomarker analysis (NT-proBNP, troponins), and electrocardiography for detecting electrophysiologic abnormalities. Management is complicated by cirrhosis, limiting the use of conventional heart failure treatments, with liver transplantation being the most definitive intervention in severe cases. Early detection of CCM is vital, particularly for patients undergoing liver transplantation or major surgery, where cardiac complications can increase mortality. Further research is necessary to refine diagnostic criteria and treatment strategies.

Monitoring psoriatic arthritis in research and clinical practice.

To discuss the varies outcome measure instruments for the assessment of different domains for psoriatic arthritis (PsA) both in trial and clinical practice settings. PsA is a multifaceted chronic inflammatory disease with diverse manifestations. This pose challenges of comprehensive assessment of the outcome of PsA. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) had developed the core domain set and in the progress of selecting the core outcome measurement set for trials and clinical practice for PsA, using the framework set by Outcome Measures in Rheumatology (OMERACT). In brief, the core set of "what to measure" has been endorsed, and a standardized way of "how to measure" them are under review. Composite outcome measures for PsA may provide a solution to measuring multiple domains in a nutshell for various purposes in trials and clinical practice. This provides a succinct summary of the current state of outcome measurement in PsA and provides a quick and comprehensive perspective to select relevant outcome measure to use in busy rheumatology clinical settings.

Being an Insider Nurse Researcher: Navigating the Challenges and Benefits to Ensure Rigour.

To provide insights into the challenges and benefits of being an insider nurse researcher in case study research. To describe strategies used to maintain rigour and trustworthiness when conducting insider research. Case study with insider research methodology was used to evaluate a nurse-led supportive care model for patients with Chronic Obstructive Pulmonary Disease and their caregivers. This paper reports a reflection on using insider research within a clinical context, utilising reflexive techniques such as journaling and discussions with academic supervisors to mitigate subjectivity. Informed consent and confidentiality were maintained to ensure ethical integrity. The study found that insider research offers both challenges and benefits. The established therapeutic relationship with patients and caregivers provided a deep understanding but also posed risks of assumptions, role conflict, and bias toward positive responses. Insider research was effective in evaluating a nurse-led model of care, providing unique insights from patients and caregivers. This discussion demonstrates the importance of reflexive practices and maintaining ethical rigour to balance roles and manage potential biases. The paper highlights both the challenges and benefits of insider research that may be helpful for other researchers. This study highlights the value of insider research in a nursing context, demonstrating how nurses can leverage therapeutic relationships to enhance patient and caregiver voices to inform evidence-based practice. It also provides practical guidance for researchers on reflexive practices to manage the potential for bias and role conflicts, and the maintenance of ethical standards to ensure the integrity and trustworthiness of the research process. The study addressed the challenges and benefits of being an insider nurse researcher in the context of evaluating a nurse-led supportive care model for patients with COPD and their caregivers. While insider research can provide unique insights, it also poses risks of assumptions, role conflict, and bias. This paper describes how these can be mitigated through reflexive techniques and integration of outsider perspectives. Established nurse-patient therapeutic relationships facilitated deeper understanding in a research setting; however, they require careful management to avoid bias. Ethical integrity was maintained through informed consent, confidentiality, and reflexive journaling. The research will impact patients and caregivers by improving their access to timely and comprehensive supportive and palliative care and offers valuable strategies for other nurse researchers to enhance the quality and trustworthiness of insider research. The development of the model of care in this study is informed by ongoing evaluation from patients with COPD and their caregivers.