Therapeutic Advances in Chronic Disease最新文献

Introduction: The pathogenesis of post-COVID interstitial lung disease, marked by lung tissue scarring and functional decline, remains largely unknown.

Objectives: We aimed to elucidate the temporal cytokine/chemokine changes in bronchoalveolar lavage (BAL) from patients with post-COVID interstitial lung disease to uncover potential immune drivers of pulmonary complications.

Design: We evaluated 16 females diagnosed with post-COVID interstitial lung disease, originating from moderate to severe cases during the second epidemic wave in the Autumn of 2020, treated at the Pneumology Department of the Arad County Clinical Hospital, Romania. Their inflammatory response over time was compared to a control group.

Methods: A total of 48 BAL samples were collected over three intervals (1, 3, and 6 months) and underwent cytology, gene, and protein expression analyses for pro/anti-inflammatory lung cytokines and chemokines using reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay.

Results: One month after infection, there were significant increases in the levels of IL-6 and IL-8. These levels decreased gradually over the course of 6 months but were still higher than those seen in control. Interferon-gamma and tumor necrosis factor alpha exhibited similar patterns. Persistent elevations were found in IL-10, IL-13, and pro-fibrotic M2 macrophages' chemokines (CCL13 and CCL18) for 6 months. Furthermore, pronounced neutrophilia was observed at 1 month post-COVID, highlighting persistent inflammation and lung damage. Neutrophil efferocytosis, aiding inflammation resolution and tissue repair, was evident at the 1-month time interval. A notable time-dependent reduction in CD28 was also noticed.

Conclusion: Our research provides insight into the immunological processes that may lead to the fibrotic changes noted in the lungs following COVID-19.

The neuropsychological functioning of people with type 1 diabetes (T1D) is of key importance to the effectiveness of the therapy, which, in its complexity, requires a great deal of knowledge, attention, and commitment. Intellectual limitations make it difficult to achieve the optimal metabolic balance, and a lack of this alignment can contribute to the further deterioration of cognitive functions. The aim of this study was to provide a narrative review of the current state of knowledge regarding the influence of diabetes on brain structure and functions during childhood and also to present possible actions to optimize intellectual development in children with T1D. Scopus, PubMed, and Web of Science databases were searched for relevant literature using selected keywords. The results were summarized using a narrative synthesis. Disturbances in glucose metabolism during childhood may have a lasting negative effect on the development of the brain and related cognitive functions. To optimize intellectual development in children with diabetes, it is essential to prevent disorders of the central nervous system by maintaining peri-normal glycemic levels. Based on the performed literature review, it seems necessary to take additional actions, including repeated neuropsychological evaluation with early detection of any cognitive dysfunctions, followed by the development of individual management strategies and the training of appropriate skills, together with complex, multidirectional environmental support.

Background: Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear.

Objectives: We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC.

Design: This is a retrospective, multicentre study of patients admitted with ASUC.

Methods: CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy.

Results: CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days).

Conclusion: CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.

Background: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT.

Objectives: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns.

Design: This is a cross-sectional survey study.

Methods: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns.

Results: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT.

Conclusion: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.

Background: The effectiveness and side effects between different medical treatments in patients with primary hyperaldosteronism have not been systematically studied.

Objective: To analyze the efficacy between different mineralocorticoid receptor antagonists (MRAs) and epithelial sodium channel (ENaC) inhibitors in a network meta-analysis (NMA) framework, while also evaluating adverse events.

Design: Systematic review and NMA.

Data sources and methods: The systematic review and NMA was reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, MEDLINE, the Cochrane library, and Excerpta Medica database (EMBASE) were searched for randomized controlled trials (RCTs) involving adult patients with primary hyperaldosteronism until 23 June 2023. Studies that compared the efficacy and side effects of different medical treatments of primary hyperaldosteronism were included. The primary outcomes included the effect on blood pressure, serum potassium, and major adverse cardiovascular events. The secondary outcomes were adverse events related to MRAs (hyperkalemia and gynecomastia). Frequentist NMA and pairwise meta-analysis were conducted.

Results: A total of 5 RCTs comprising 392 participants were included. Eplerenone, esaxerenone, and amiloride were compared to spironolactone and demonstrated comparable effect on the reduction of systolic blood pressure. In comparison to spironolactone, eplerenone exhibited a less pronounced effect on reducing diastolic blood pressure [-4.63 mmHg; 95% confidence interval (CI): -8.87 to -0.40 mmHg] and correcting serum potassium (-0.2 mg/dL; 95% CI: -0.37 to -0.03 mg/dL). Spironolactone presented a higher risk of gynecomastia compared with eplerenone (relative risk: 4.69; 95% CI: 3.58-6.14).

Conclusion: The present NMA indicated that the blood pressure reduction and potassium-correcting effects of the three MRAs may demonstrate marginal differences, with confidence levels in the evidence being very low. Therefore, further research is needed to explore the efficacy of these MRAs, especially regarding their impact on mortality and cardiovascular outcomes.

Trial registration: PROSPERO (CRD: 42023446811).

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery.

Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy.

Design: This was a single-center retrospective cohort study.

Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis.

Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387).

Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

Background: Cervical cancer poses a considerable worldwide health issue, where infection with the human papillomavirus (HPV) plays a vital role as a risk factor. Photodynamic therapy (PDT) is a minimally invasive treatment for HPV-related cervical lesions, which uses photosensitizers and light to selectively destroy abnormal cells.

Objectives: Our objective is to present a comprehensive overview of the different types of molecules employed in PDT to reduce the occurrence and fatality rates associated with cervical cancer.

Design: Scoping review and bibliometric analysis.

Methods: The article explores clinical trials investigating the efficacy of PDT in treating low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion, as well as preclinical approaches utilizing various molecules for PDT in cervical cancer. Furthermore, the article sheds light on potential molecules for PDT enhancement, examining their properties through computer modeling simulations, molecular docking, and assessing their advantages and disadvantages.

Results: Our findings demonstrate that PDT holds promise as a therapeutic approach for treating cervical lesions associated with HPV and cervical cancer. Additionally, we observe that the utilization of diverse dye classes enhances the anticancer effects of PDT.

Conclusion: Among the various molecules employed in PDT, functionalized fullerene exhibits a notable inclination toward overexpressed receptors in cervical cancer cells, making it a potential candidate for intensified use in PDT. However, further research is needed to evaluate its long-term effectiveness and safety.

Background: Enteropathic spondyloarthritides (eSpAs) are chronic inflammatory joint diseases associated with inflammatory bowel disease (IBD). Limited data are available on the prevalence since arthritis in IBD patients may be underestimated because medications may hide disease activity with a possible diagnostic delay.

Objectives: We aimed to evaluate diagnostic delay in eSpA and explore associated demographic, clinical, and radiographic characteristics.

Design: Single-centre cross-sectional study conducted on consecutive out-patients referred to the combined Gi-Rhe clinic (November 2018-October 2019).

Methods: We analysed eSpA patients for diagnostic delay, disease activity, inflammatory markers, conventional radiography (CR) and magnetic resonance images (MRI) of sacroiliac joints/spine.

Results: A total of 190 eSpA patients [118 peripheral SpA, 72 axial (Ax) SpA including 44 non-radiographic (nr)-axSpA] were enrolled. axSpA patients had a higher prevalence of men sex, HLA-B27 positivity, uveitis and pancolitis compared with peripheral eSpA. Median diagnostic delay in eSpA was 48 months (IQR 6-77) with no difference between axial and peripheral patients. Radiographic-axial SpA (r-axSpA) patients displayed a higher diagnostic delay compared with nr-axSpA (median/IQR 36/17-129 versus 31/10-57 months, p = 0.03) and were older, with longer disease duration, low education status and high rate of employment than patients with nr-axSpA. r-axSpA patients with sclerosis, syndesmophytes and bridge at CR had higher diagnostic delay than those without lesions. Men showed higher prevalence of spine damage lesions than women as sclerosis, squaring, syndesmophytes and bridges. Longer disease duration was detected in patients with radiographic damage as bridge and sacroiliitis grade 3. On MRI, sacroiliac bone oedema was associated with reduced diagnostic delay, whereas bone erosions were associated with higher diagnostic delay compared with that in patients without these lesions. Patients with psoriasis displayed a higher diagnostic delay compared to those without skin involvement.

Conclusion: Diagnostic delay was higher in r-axSpA compared with nr-axSpA despite the same treatment. Demographic, clinical features and radiological lesions were associated with diagnostic delay.

Background: Non-communicable diseases (NCDs) are the leading cause of mortality worldwide, and increasingly so in low- and middle-income countries. Afghanistan is dealing with a double burden of diseases, yet there has been no evidence synthesis on the prevalence of major NCDs and their risk factors.

Objective: This study aims to provide a comprehensive synthesis of the existing data on the prevalence of major NCDs and the common related risk factors in Afghanistan.

Method: We systematically reviewed scientific articles from 2000 to 2022 that reported the prevalence of diabetes, chronic respiratory diseases (CRDs), cardiovascular diseases (CVDs) or cancer, and their risk factors in Afghanistan. Four online databases (PubMed, Web of Science, Cochrane and Google Scholar) and two local journals in Afghanistan (not indexed online) were systematically searched and screened. Two reviewers independently screened and appraised the quality of the articles. Data extraction and synthesis were performed using tabulated sheets.

Results: Among 51 eligible articles, 10 (19.6%) focused on cancer, 10 (19.6%) on diabetes, 4 (7.8%) on CVDs, 4 (7.8%) on CRDs and 23 (45.1%) on risk factors as the primary outcome. Few articles addressed major NCD prevalence; no evidence of CVDs, cancer was 0.15%, asthma ranged between 0.3% and 17.3%, and diabetes was 12%. Pooled prevalence of hypertension and overweight were 31% and 35%, respectively. Central obesity was twice as prevalent in females (76% versus 40%). Similarly, gender differences were observed in smoking and snuff use with prevalence rates of 14% and 25% among males and 2% and 3% among females, respectively. A total of 14% of the population engaged in vigorous activity. Pooled prevalence for physical inactivity, general obesity, fruit and vegetable consumption, dyslipidaemia and alcohol consumption couldn't be calculated due to the heterogeneity of articles.

Conclusion: Only little evidence is available on the prevalence of major NCDs in Afghanistan; however, the NCD risk factors are prevalent across the country. The quality of the available data, especially those of the local resources, is poor; therefore, further research should generate reliable evidence in order to inform policymakers on prioritizing interventions for controlling and managing NCDs.