Therapeutic Advances in Chronic Disease最新文献

Background: Nonacid gastroesophageal reflux-induced cough (GERC) remains understudied, with limited research on effective treatment options. Recently, neuromodulators such as gabapentin and baclofen have shown promise in managing nonacid GERC.

Objectives: This study aimed to identify factors associated with response to neuromodulator therapy in nonacid GERC.

Study design: A retrospective study.

Methods: We analyzed medical records of patients diagnosed with nonacid GERC who received gabapentin or baclofen as an add-on therapy enrolled between December 2019 and January 2024. Retrospective analysis of general information, cough-related questionnaires, MII-pH parameters, and other assessments was conducted to establish a regression analysis model for identifying multiple factors associated with neuromodulator response.

Results: In this retrospective cohort study, data from 184 patients were analyzed, with 106 (57.6%) classified as responders and 78 (42.4%) as nonresponders. Clinical factors significantly associated with neuromodulator efficacy included gender (OR = 4.324, p = 0.027), age (OR = 0.803, p = 0.002), and exposure to cough-aggravating factors (OR = 6.345, p < 0.001). Furthermore, multiple regression analysis further identified specific Hull Airway Reflux Questionnaire (HARQ) items-"Cough with certain foods" (OR = 2.523, p = 0.034), "Cough with eating" (OR = 4.445, p < 0.001), and "Cough brought on by singing or speaking" (OR = 5.003, p = 0.007)-as significant predictors. Additionally, Medication Adherence Questionnaire (MAQ) items such as "Forgetfulness" (OR = 0.257, p = 0.005) and "Stopping medication when "feeling better" (OR = 0.787, p = 0.017) were also identified as significant predictors of treatment response.

Conclusion: Neuromodulators can relieve nonacid GERC in patients unresponsive to standard anti-reflux therapy. Factors such as male gender, younger age, less exposure to cough irritants, and higher HARQ and lower MAQ scores can effectively predict the efficacy of neuromodulators.

Background: Hepatocellular carcinoma (HCC) is a major global health issue, in which the underlying liver disease aetiology has shifted towards non-viral causes, particularly metabolic (dysfunction)-associated fatty liver disease (MAFLD). While traditionally associated with cirrhosis, a subset of HCC cases arises in patients with MAFLD but without cirrhosis, whose characteristics remain poorly understood.

Objectives: The study aims to explore the clinical, tumour and genetic characteristics of non-cirrhotic MAFLD-related HCC when compared to those that develop in the context of cirrhosis.

Design: A multi-centre, retrospective study of 89 MAFLD-related HCC patients enrolled between 2009 and 2023 was performed.

Methods: We conducted a study of well-defined MAFLD-related HCC patients to explore their MAFLD-related clinical and genetic associations. Statistical analysis was undertaken to compare the underlying cirrhosis and non-cirrhosis groups for HCC features, adjusting for relevant confounders.

Results: Patients with HCC arising in cases of MAFLD without cirrhosis exhibited a lower body mass index, higher triglyceride levels and increased smoking prevalence compared to their counterparts with cirrhosis. Despite arising in the absence of cirrhosis, these patients had more aggressive tumour features, including larger tumour size, multifocality and portal vein thrombosis. Logistic regression confirmed non-cirrhosis status to be an independent predictor of larger tumour size and increased lesion number.

Conclusion: Non-cirrhotic MAFLD-related HCC presents with distinct clinical and tumour characteristics, suggesting the existence of unique disease drivers that are yet to be discovered.

Background: In recent decades, the prevalence of dyslipidemia, especially high low-density lipoprotein cholesterol (LDL-C), has risen sharply in China. Although lifestyle interventions are important, traditional face-to-face approaches have limitations. Digital Therapeutics (DTx) can provide an effective solution by delivering remote medical interventions to patients via software and hardware, thereby optimizing existing clinical treatment methods with enhanced convenience and accessibility.

Objectives: This study aims to explore the current evidence on the effect of lifestyle intervention-based Digital Therapeutics (LI-DTx) on high LDL-C, and to analyze their advantages and disadvantages.

Eligibility criteria: This scoping review examines clinical studies assessing the effects of DTx on LDL-C levels. Papers were included in the final analysis if there was evidence that DTx had effects on lowering LDL-C levels.

Sources of evidence: Papers that were published between January 2014 and December 2023 were included in the PubMed database.

Charting methods: Data extracted from the publications included country, year, study type, study population, sample size, study duration, intervention, and changes in LDL-C level.

Results: A total of 23 target literature were identified. Twenty-one studies confirmed that LI-DTx could optimize the LDL-C level through remote lifestyle interventions such as diet, exercise, medication, and health education, of which 14 studies reported a significant reduction in LDL-C level (p < 0.05). In the future, the development and design of DTx will need to improve intelligence, personalization, applicability, real-time performance, and data security; integrate with traditional healthcare systems; facilitate multidisciplinary collaboration in dyslipidemia management; and enhance long-term patient engagement with DTx platforms.

Conclusion: LI-DTx may offer a more effective and sustainable solution for LDL-C management, although several challenges remain. Further randomized controlled clinical trials are needed to provide scientific support for its efficacy and safety.

Cardiovascular disease (CVD) still poses a significant risk for morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). For a long time, among functional parameters, only the forced expiratory volume in 1 s (FEV₁) has been considered as predictive of cardiovascular (CV) mortality especially in elderly patients in fact, there is evidence that reductions in lung function indices can increase the risk of ischaemic heart diseases and cerebrovascular diseases, independently from other risk factors. Now, there is considerable evidence suggesting that hypoxemia, systemic inflammation, oxidative stress and hyperinflation may lead to an early sub-clinical CV involvement in patients affected by COPD. Ageing in itself impacts specific aspects of the CV system, including reduced beta-adrenergic responsiveness, increased vagal tone and myocardial and vascular stiffness, endothelial dysfunction, diminished arterial baroreflex and compromised diastolic function. The complex involved interactions include ageing mechanisms as well as multiple known and unknown (e.g. genetic) risk factors. CVDs are leading causes of mortality in individuals with impaired lung function and the two entities commonly coexist with poor outcomes in patients experiencing both conditions. However, the precise mechanisms responsible for this association remain largely unknown. In this narrative review, we summarize current knowledge regarding the co-occurrence of COPD and CVD focusing on the shared biological pathways and biological mechanisms involved in these conditions.

Background: Klotho is a kidney-derived protein that is involved in various kidney diseases. The role of serum soluble Klotho (sKlotho) in the anemia of patients undergoing hemodialysis has not been well characterized.

Objective: We aimed to characterize the relationship between sKlotho and hemoglobin (Hb) levels in this group of patients.

Design: A single-center cross-sectional study of 208 patients undergoing maintenance hemodialysis (MHD) and 50 healthy controls was performed between June 1 and 31, 2023.

Methods: Demographic information and biomedical parameters, such as age, body mass index, medication use, and their Hb, albumin, interleukin-6, and sKlotho concentrations, were obtained. Patients undergoing MHD were allocated to a group that achieved the Hb target (⩾110 g/L) and a group that did not (<110 g/L). Correlation analysis and multivariate logistic and linear regression analyses were performed to evaluate the relationship of sKlotho with Hb concentration.

Results: Participants undergoing MHD had lower Hb and sKlotho concentrations than controls. Those who had not achieved the target Hb level were given fewer erythropoiesis-stimulating agents and had lower sKlotho and albumin concentrations, but higher interleukin-6 concentrations, than those who had achieved the Hb target. The sKlotho concentration positively correlated with the Hb concentration and was inversely associated with the incidence of a lack of achievement of the target Hb level. Multivariate logistic regression models revealed that there was a close association between sKlotho and a lack of achievement of the target Hb level after adjustment for potential confounders (odds ratio: 0.335, 95% confidence interval: 0.142-0.791, p = 0.013). This relationship was closer on multivariate linear regression analysis when sKlotho was included as a continuous variable.

Conclusion: The circulating sKlotho concentration is very low, but deficiency of this protein is independently associated with a high risk of anemia in patients undergoing MHD. Therefore, the routine monitoring of sKlotho concentration might be useful in the management of renal anemia in such patients.

Background: With rising obesity rates worldwide, clinical trials focused on identifying effective treatments are increasing. While guidelines exist for pharmaceutical drugs targeting obesity, there are none for herbal medicine clinical trials for anti-obesity. Both industries refer to the same guidelines for clinical trials.

Objectives: This scoping review aimed to gather information from herbal medicine anti-obesity randomised controlled trials (RCTs), analyse the methodologies and assess their alignment with international guidelines.

Eligibility criteria: This review included RCTs of participants of all ages with obesity utilising herbal medicine with any comparators and focusing on various outcome measures.Sources of evidence: Only published journal articles were included.

Charting methods: Articles were extracted from MEDLINE, CENTRAL and EMBASE using predetermined keywords. Relevant data, such as the study characteristics, types of herbal interventions and controls, treatment durations, outcome measures and safety monitoring methods were recorded in a table format for comparative analysis.

Results: We included 99 RCTs that showed participant sample sizes ranging from 8 to 182, ages 18 to 80 years and body mass indexes (BMIs) between 25 and 49.9 kg/m². Herbal interventions used single herbs (n = 57) and mixtures (n = 42), given for 14 days to 56 weeks. Studies implementing diet modifications include restricted calorie diets (n = 35), food-portion controlled diets (n = 7) and fixed calorie diets (n = 7). Of the 28 studies implementing exercise, most were of moderate intensity (n = 22). All studies collected BMI and weight as primary outcomes. Body fat composition was measured in over 50% of studies using a body analyser (n = 57). Waist, hip and abdominal circumferences were infrequently measured. Radiological tools used include dual-energy X-ray absorptiometry (n = 16), computed tomography scans (n = 10) and ultrasound (n = 2). Safety monitoring methods were reported in most studies (n = 76).

Conclusion: In conclusion, almost 50% of the studies adhered to international pharmaceutical clinical trial guidelines, addressing dietary, lifestyle, physical activity and cardiovascular risk factors. Nonetheless, more herbal anti-obesity studies need to consider the assessment of weight maintenance.

Background: Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension and can be effectively managed, or even cured, with targeted treatment. Despite this, it remains largely undiagnosed leaving a significant patient population with resistant hypertension and modifiable cardiovascular risk.

Objective: To determine expert consensus on key information about PA that should ideally be taught to medical students as a step toward improving the detection of this common, underdiagnosed, and often easily treated condition.

Design: The study employed a modified Delphi method which consisted of three rounds, the first of which contained an open-ended question about key areas that experts believe to be most important for inclusion in medical teaching resources and then progressing to assessment of individual versus group rankings of consensus items. Experts included both clinician-educator-researchers and patients with lived experience.

Results: Nine critical knowledge areas in epidemiology, diagnostics, and pathophysiology were identified by the Delphi as consensus items, with the highest ranked being: "PA is common but often under-diagnosed - think about it with every hypertensive patient."

Conclusion: Experts reached a consensus, for the first time, on nine critical knowledge areas about PA that should be covered in medical education. Importantly, the consensus accounted for patients' values and decisions. The results of this study could be used to assess medical student knowledge and their learning resources to facilitate curriculum development and medical resource updates to ensure the timely and accurate diagnosis of PA in hypertensive patients.

Background: Increasing evidence suggests that immunophenotypes play a crucial role in Metabolic dysfunction-associated fatty liver disease (MAFLD), but the specific immunophenotypes contributing to its pathogenesis remain unclear.

Objectives: This study aimed to elucidate the causal associations between immunophenotypes and MAFLD and identify the underlying mediation pathways involved.

Design: Mendelian randomization (MR) study.

Methods: This study is a quasi-causal inference analysis using univariable and multivariable MR (UVMR and MVMR). Five MAFLD genome-wide association studies (GWASs) and the largest immunophenotype GWAS were analyzed to assess their causal associations. Two-step MR identified potential mediators and quantified their mediation proportions. Comprehensive MR methods, multiple sensitivity analyses, meta-analyses, and false discovery rate (FDR) further enhanced the robustness of our findings.

Results: Pooled inverse-variance weighted (IVW) estimates in UVMR identified 47 immunophenotypes having a suggestive causal association with MAFLD. After adjusting for FDR, three lymphocyte phenotypes remained significant: CD20 on IgD^-CD24^- B cells (OR: 1.035, p _fdr: 0.006), terminally differentiated CD8⁺ T cells %T cells (OR: 1.052, p _fdr: 0.006), and CD4 on CD39⁺ secreting CD4⁺ regulatory T cells (OR: 1.036, p _fdr: 0.046). Meta-analysis of IVW MVMR estimates with confounders adjustment confirmed that CD20 on IgD^-CD24^- B cells and terminally differentiated CD8⁺ T cells %T cells had significant direct causal associations on MAFLD (p _fdr < 0.05). Additionally, two-step MR analysis identified the waist-to-hip ratio as a mediator, accounting for 42.64% of the causal association between CD20 on IgD^-CD24^- B cells and MAFLD.

Conclusion: The causal associations of three lymphocyte phenotypes with increased MAFLD risk were identified in this study. CD20 on IgD^-CD24^- B cells may both directly and indirectly elevate MAFLD risk, while terminally differentiated CD8⁺ T cells have a direct causal relationship with MAFLD. These findings suggest new possibilities for targeted therapies and underscore the potential for personalized immunotherapy in managing MAFLD.

Background: The application of biologic agents has benefited patients with Behcet's uveitis (BU) who do not respond to conventional treatment regimens. However, there is currently no consensus on the optimal treatment regimen of interferon alpha-2a (IFN-α2a) for refractory BU.

Objectives: To evaluate treatment outcomes and safety of IFN-α2a in a large series of refractory BU patients and to explore whether nonbiologic immunomodulatory agents (cyclosporin A) other than corticosteroids should be concomitantly used.

Design: We conducted a retrospective cohort study, which included 153 BU patients who received IFN-α2a treatment between December 2012 and September 2023 with a minimum duration of 6 months.

Methods: Best-corrected visual acuity (BCVA), the frequency of uveitis relapse, corticosteroid-sparing effect, and side effects were evaluated.

Results: Of the 153 patients enrolled, 87 patients were treated with IFN-α2a plus corticosteroids (IC), and 66 patients were treated with IFN-α2a plus corticosteroids and cyclosporin A (ICC). Both IFN-α2a treatment regimens significantly improved BCVA as early as 2 months following treatment, and the improvement was maintained over at least a 2-year follow-up. At the final visit, 86.8% and 73.1% of the affected eyes in the ICC and IC groups achieved improved or stable vision, respectively. The ICC regimen was more effective at improving vision (p = 0.01). Overall, the frequency of uveitis relapse and the dose of oral prednisolone were significantly reduced in both groups after treatment (all p < 0.0001). However, there were no statistically significant differences in these parameters between the two groups. None of the included patients experienced serious side effects that led to the discontinuation of IFN-α2a therapy.

Conclusion: IFN-α2a treatment is a promising option for patients with refractory BU. Our results showed that cyclosporin A as an adjunct could enhance the therapeutic effect of IFN-α2a.