Therapeutic Advances in Chronic Disease最新文献

Background: Acute esophagogastric variceal bleeding (AEGVB) is a common complication of liver cirrhosis and hepatocellular carcinoma (HCC). It is unclear if older patients with cirrhotic HCC benefit from endoscopic treatment as secondary prophylaxis for AEGVB in short term.

Objectives: We aim to investigate if endoscopic treatment as secondary prophylaxis for AEGVB reduces short-term mortality in older patients with cirrhotic HCC.

Design: We retrospectively enrolled 138 consecutive patients over 60 years old with cirrhotic HCC and AEGVB from April 1, 2021 through December 31, 2022 in Emergency Room, Beijing You'an Hospital, Capital Medical University.

Methods: A 1:1 propensity score matching (PSM) analysis was performed to adjust for confounding factors such as age, gender, Child-Pugh score in our statistical findings. Logistic regression and Cox regression analyses were used to investigate whether there was a significant negative association between endoscopic treatment and short-term mortality for AEGVB in older patients with cirrhotic HCC. Kaplan-Meier methodology was employed to compare overall survival over 6 weeks between the endoscopic treatment group and non-endoscopic treatment group.

Results: In older patients with cirrhotic HCC and AEGVB, in-hospital mortality and 6-week mortality were significantly lower in the endoscopic treatment group compared to the non-endoscopic treatment group before PSM (5.33% vs 26.98%, p = 0.001 for in-hospital mortality; 12.00% vs 44.44%; p < 0.001 for 6-week mortality). These results remained consistent after PSM (4.76% vs 26.98%, p = 0.002 for in-hospital mortality; 9.52% vs 44.44%; p < 0.001 for 6-week mortality). Both logistic regression and Cox regression analyses found that endoscopic treatment contributed to reduced short-term mortality for AEGVB in older patients with cirrhotic HCC. Kaplan-Meier survival curves indicated that older patients undergoing endoscopic treatment had a higher short-term survival rate than those who didn't receive endoscopic treatment in our cohort. However, there was no significant difference in short-term survival between patients receiving endoscopic variceal ligation and those treated with endoscopic injection sclerotherapy.

Conclusion: Secondary prophylaxis of endoscopic treatment helps to reduce 6-week mortality for AEGVB in older patients with cirrhotic HCC. Therefore, endoscopic treatment is suggested to be employed as secondary prophylaxis in this special population in clinical practice.

Background: The impact of Mitochondrial Myopathy (MM) symptoms on functional ability across activities of daily living (ADLs) has not been fully characterized, nor is it understood how MM patients define their key symptoms. Furthermore, it is unclear what MM individuals perceive as a clinically meaningful improvement.

Objective: We sought to characterize how MM patients feel about their symptoms in the key MM domains of muscle weakness, muscle fatigue, exercise intolerance, imbalance, and peripheral neuropathy; as well as their functional ability.

Design: We conducted a single-center, observational, qualitative study that involved standardized structured and semi-structured patient interviews.

Methods: Most interview questions were open-ended, allowing individuals to provide personalized narratives that were transcribed in real time. A total of 33 individuals with MM were interviewed either in-person or remotely. Interview transcripts underwent thematic analysis in accordance with grounded theory. Data was presented using a mixed-methods approach.

Results: Subjects provided extensive narratives that demonstrated the substantial and widespread impact of MM across many aspects of MM patient lives, including the impact of each MM domain of muscle weakness, muscle fatigue, exercise intolerance, imbalance, and peripheral neuropathy on ADLs; the need to adapt to preserve independence and quality of life (QOL); impaired self-perception, participation in social activities, hobbies, and relationships; and change in circumstances over time.

Conclusion: These meaningful insights highlight the critical and emergent need for approved drug treatment(s) in this profoundly burdened patient population. Our results will serve as a comprehensive resource to inform the physician, patient, industry and advocacy communities on outcome measure selection and clinical trial design; and to help inform regulatory agencies in the United States Food and Drug Administration (FDA) drug approval process for MM.

Background: Lymphomas represent various groups of cancers. Its treatment has a cytotoxic effect on all body tissues, especially female ovaries, yielding premature ovarian insufficiency.

Objectives: This study aimed to compare the fertility and ovarian preserving role of gonadotropin-releasing hormone agonists (GnRH-a) when administered in conjunction with chemotherapy in women treated for lymphomas.

Design: Only prospective clinical trials were included in this systematic review.

Data sources and methods: We searched for pertinent studies in PubMed, Web of Science, Cochrane Library, Google Scholar, and Scopus till April 2025. Available prospective clinical trials comparing patients with Hodgkin lymphoma and non-Hodgkin lymphoma receiving concurrent chemotherapy and GnRH-a with patients receiving chemotherapy alone were included. The main outcomes were cyclic ovarian function (COF), pregnancy rate, follicle-stimulating hormone (FSH) level, luteinizing hormone level, estradiol level, and anti-Mullerian hormone (AMH) level. Cochrane's risk of bias tool for clinical trials was used for the risk of bias assessment, and all the included studies were deemed of acceptable quality.

Results: Twelve prospective clinical trials involving 733 women were analyzed, with 374 patients receiving GnRH-a and 359 as controls. The mean age of the GnRH-a group was 25.86 years, compared to 27.62 years in the control group. GnRH-a administration was associated with a notably higher COF, higher pregnancy rates, lower FSH levels, and higher AMH levels compared to controls. No significant difference between the groups was observed in estradiol levels.

Conclusion: Co-administration of GnRH-a during chemotherapy in women with lymphoma appears to offer a protective effect against ovarian damage and supports fertility preservation in women with lymphoma. These findings advocate for the integration of GnRH-a into fertility preservation strategies, emphasizing its potential to improve long-term reproductive health in this vulnerable patient population. However, further high-quality, large-scale studies are warranted to standardize protocols and confirm these findings for broader clinical applications.

Background: In the context of the COVID-19 pandemic, there is growing concern about the virus's effects on individuals with existing endocrine disorders such as primary aldosteronism (PA).

Objectives: This study explores the potential relationship between PA and the risk of developing obstructive sleep apnea (OSA) after a COVID-19 infection.

Design: In this retrospective cohort study, we utilized data from the TriNetX database, covering the period from January 2019 to January 2023. We identified essential hypertension (EH) patients as the control group, employing 1:1 propensity score matching.

Methods: The endpoints included incident OSA and all-cause mortality.

Results: Among 11,422,001 patients with PCR-positive COVID-19, we identified 3628 PA patients (mean 63.1 years, male 38.1%). After a median follow-up of 1.9 years, the rate of OSA was 28.9 per 1000 person-years in PA patients compared to EH with 16.7. We showed a significant increase in incident OSA (adjusted hazard ratio (aHR) 1.58, p < 0.001) and mortality (aHR 1.12, p = 0.04) in PA patients than EH post-COVID-19. The horizon plot revealed that patients with pre-existing PA had the highest risk of OSA at 2 months (aHR = 2.34) post-COVID-19. In subgroup analysis, PA patients with a high body mass index (⩾30 kg/m²; aHR 1.81, p = 0.001) or preserved kidney function (aHR 2.00, p < 0.001) had increased OSA incidences post-COVID-19.

Conclusion: Our study underscores a notable rise in incident OSA among PA patients post-COVID-19, highlighting the imperative for diligent OSA screening, particularly among individuals with obesity or preserved kidney function.

Background: Musculoskeletal disorders (MSKDs) are the leading cause of disability worldwide. The associations between socioeconomic and lifestyle factors and MSKDs have been widely studied in Europe and North America. However, little data are available about their relationship in Latin America.

Objectives: To estimate the prevalence of chronic MSKDs in Brazil and assess their relationship with socioeconomic and lifestyle factors.

Design: This is a cross-sectional study, based on a subanalysis of the open-access database from the Brazilian National Health Survey 2019. This survey was a nationwide, cross-sectional, door-to-door study that included 87,648 adults and was conducted between 2019 and 2020.

Methods: Prevalence estimates were based on weighted sample strata, and the relationship between MSKD and socioeconomic and lifestyle factors was examined through network analysis and weighted Poisson regression models with robust variance.

Results: The weighted prevalence of chronic MSKDs was estimated at 26.1% (95% confidence interval, 25.5%-26.8%). In the network analysis, including all socioeconomic and lifestyle variables, MSKDs prevalence was notably linked to higher body mass index, drinking, smoking, and low income. In the regression models, MSKD prevalence was associated with obesity, sleep disorders, smoking, alcohol consumption, and depression, and inversely associated with physical activity, even after controlling for the sociodemographic disparities.

Conclusion: This study identifies specific socioeconomic and lifestyle factors associated with MSKDs and highlights the need for immediate national health promotion programs focused on MSKDs prevention through targeted lifestyle modifications, especially in populations belonging to the lower-income strata in Brazil.

Background: The "credibility" and "expectation" regarding the treatment are important factors in the rehabilitation management of patients with spinal pain (SP).

Objectives: The aim of this study was to translate, culturally adapt, and validate an Italian version of the credibility/expectancy questionnaire (CEQ-I) by Devilly and Borkovec (CEQ) for its application in SP in rehabilitative care.

Design: Cross-sectional observational study.

Methods: Ninety-nine patients (N = 99; mean age of 56.9 years ± 16.3 SD) with acute or chronic SP were recruited from September 2023 to September 2024. To evaluate construct validity, exploratory factor analysis (EFA) was conducted using a matrix of polychoric correlations along with promax rotation. The internal consistency and stability of the scale were evaluated using Cronbach's alpha coefficient and test-retest analysis through the intraclass correlation coefficient (ICC). Pearson's analysis between CEQ and other scales (Numeric Rating Scale, NRS; Roland and Morris-Disability Questionnaire, RMDQ; Oswestry Disability Index, ODI; Neuropathic Pain Symptom Inventory, NPSI) was employed to assess external validity.

Results: Ninety-nine subjects were recruited. Test-retest reliability between two consecutive administrations of the CEQ showed an ICC of 0.90 (p < 0.001). The Kaiser-Meyer-Olkin (KMO) statistic was 0.81, indicating suitability for factor analysis. EFA revealed two factors-credibility and expectancy-accounting for 56.6% of the variance. Cronbach's alpha indicated high internal consistency (0.85). External validation using Pearson's correlation found no significant relationships between the CEQ subscale scores and NRS, RMDQ, ODI, and NPSI scales.

Conclusion: The CEQ-I is a valid Italian translation of CEQ that demonstrates acceptable psychometric properties in SP in a rehabilitative setting. However, we recommend further analysis of the construct definition of the CEQ-I.

Background: Antiretroviral therapy (ART) has significantly reduced morbidity and mortality among people living with HIV (PLWH). However, data on the burden of metabolic syndrome (MetS) in sub-Saharan Africa remains limited, particularly following the implementation of universal test-and-treat strategies and the widespread use of integrase inhibitor-based combinations.

Objective: This study aimed to determine the prevalence and associated factors of MetS among adults receiving first-line ART in the Hawassa City Administration, southern Ethiopia.

Design: A cross-sectional study.

Methods: The study was conducted from January 2023 to May 2024, adapting the World Health Organization (WHO) stepwise approach to collect data. All study-relevant data were collected from participants using a pretested structured questionnaire. MetS was defined according to the 2009 harmonized criteria. A binary logistic regression analysis was conducted to identify predictors of MetS, with adjusted odds ratio (aOR) and 95% confidence intervals (CIs).

Results: A total of 450 adults participated in the study, of whom 262 (58.2%) were females. The mean (standard deviation) age of the participants was 41.1(±9.7) years. The prevalence of MetS was 36.4% (95% CI: 32.2-41.6), with low high-density lipoprotein (HDL) cholesterol as the most frequent component observed in 368 (81.8%) participants. Age >50 years (aOR: 2.9; 95% CI: 1.4-6.2), alcohol use (aOR: 2.7; 95% CI: 1.2-6.4), body mass index ⩾25 kg/m² (aOR: 3.7; 95% CI: 1.9-7.1), triglyceride/HDL-cholesterol ratio (aOR: 1.5; 95% CI: 1.3-1.7), family history of hypertension (aOR: 2.1; 95% CI: 1.1-3.8), and high waist-height ratio (aOR: 5.4; 95% CI: 1.8-15.9) were significantly associated with MetS. However, dolutegravir-based first-line regimens were not significantly associated with MetS (p=0.482 for DTG initiation, and p=0.34 for switching to DTG).

Conclusion: The noticeable prevalence of MetS among PLWH highlights its potential to increase cardiovascular risks. Therefore, routine screening of PLWH for components of MetS is essential to reduce the health risks associated with metabolic disorders. As most of the identified risk factors are modifiable, implementing lifestyle interventions is also imperative.

Background: Sodium harmony is closely correlated with the progression of chronic kidney disease (CKD).

Objectives: The current study aims to explore the significance of the circadian rhythm of urinary sodium excretion in CKD management and to help establish individualized salt restriction strategies.

Design: This is a prospective study among inpatients with CKD.

Methods: The study included 715 participants with CKD from the Third Affiliated Hospital of Sun Yat-Sen University. Multivariable Cox regression models and restricted cubic splines were employed to explore the independent and joint associations of 24-h urinary sodium and sodium rhythm with prognosis of CKD.

Results: During a median follow-up of 6.92 years, 286 major renal events, 112 MACE, 160 deaths, and 321 composite events were documented. 24-h urinary sodium was not associated with any outcomes. However, there were dose-response associations of diurnal sodium/24-h urinary sodium with major renal events (p _overall < 0.001, p _nonlinearity = 0.016) and composite events (p _overall < 0.001, p _nonlinearity = 0.129). Compared with the combination of low 24-h sodium and normal sodium rhythm, the combination of high 24-h sodium and abnormal sodium rhythm had the highest risk of incident major renal events (hazard ratio, 1.62; 95% confidence interval, 1.04-2.51). A significant interaction was observed between sodium intake and sodium rhythm in associations with composite events (p for interaction = 0.015).

Conclusion: The circadian rhythm of sodium excretion emerges as a novel and potentially more sensitive risk factor for the prognosis of CKD. Furthermore, the association between sodium intake and progression of CKD was notably pronounced among individuals with abnormal sodium rhythms. Efforts to implement individualized salt restriction strategies are warranted.

Background: Steroid-refractory ulcerative colitis (SR-UC) is a severe form of ulcerative colitis (UC) that persists despite high-dose corticosteroid therapy. Management is challenging and often requires biologics, immunosuppressants or colectomy. Tacrolimus, a calcineurin inhibitor with immunomodulatory effects, has emerged as a potential alternative, though its efficacy, safety and long-term outcomes remain uncertain.

Objectives: This systematic review evaluates the efficacy and safety of tacrolimus in SR-UC, compares it with anti-tumour necrosis factor (TNF) agents, and examines its role in patients with steroid-refractory ulcerative proctitis (SR-UP).

Design: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were assessed using the Oxford Centre for Evidence-Based Medicine framework.

Data sources and methods: A comprehensive search of PubMed and Medline (1998-2025) identified studies reporting clinical remission, response rates, adverse effects and colectomy rates. Subgroup analyses compared oral tacrolimus with anti-TNF therapy and evaluated topical tacrolimus in SR-UP.

Results: Seventeen studies (658 patients) met the inclusion criteria. Tacrolimus demonstrated variable efficacy, with clinical remission rates of 9.4%-75.6% and response rates of 28.6%-89.6%. Adverse events, mainly neurotoxicity and nephrotoxicity, occurred in 16.7%-53.0% of cases, sometimes leading to treatment discontinuation. Colectomy rates ranged from 6.1% to 62%. No significant difference was observed between tacrolimus and anti-TNF agents in remission induction, though anti-TNFs had superior long-term outcomes. Topical tacrolimus showed promising efficacy in SR-UP (73.0%-75.0% remission) but was associated with high adverse event rates (45.0%-67.0%).

Conclusion: Tacrolimus is a viable option for SR-UC, particularly in combination therapy, but its long-term efficacy remains uncertain. While it is comparable to anti-TNFs for short-term remission, high colectomy rates and adverse effects require careful monitoring. Topical tacrolimus shows promise for SR-UP but requires standardised dosing. Further large-scale trials are needed to optimise treatment strategies and evaluate long-term safety.

Trial registration: The review has been registered with PROSPERO (CRD42023432827), the international prospective register of systematic reviews.

Background: Rosacea is a common inflammatory disease. Four clinical rosacea subtypes have been described, with the papulo-pustular being the most common. At present, the only FDA-approved treatment for papulo-pustular rosacea is low-dose doxycycline. Retinoids, in particular isotretinoin, have shown for decades positive outcomes in the treatment of rosacea, but due to the lack of robust evidence, they are still considered an off-label treatment for this condition.

Objectives: Summarize the current evidence in the literature regarding the role of topical and systemic retinoids in the treatment of papulo-pustular rosacea.

Design: Systematic review and meta-analysis.

Data source and methods: A systematic MEDLINE, EMBASE, and Cochrane search of relevant publications on this topic was carried out. Randomized and non-randomized studies regarding topical and systemic retinoid treatment for rosacea were included. We excluded not relevant studies, case reports, reviews, and non-English language studies. We have used RoB2 and ROBINS-1 tool for assessing risk of bias in randomized and non-randomized trials, respectively.

Results: Due to the heterogeneity in study design and outcomes reporting, the standardization of our results is limited, but the findings from this systematic review with meta-analysis indicate that retinoids, particularly isotretinoin, are a promising treatment option for papulopustular rosacea, with a favorable tolerability and safety profile. On the other hand, available data for topical retinoid therapy are less definitive and more contradictory, with only two randomized studies reporting opposite outcomes.

Conclusion: Retinoids may be a valid treatment option for rosacea, but larger, randomized controlled trials are needed to establish standardized dosing regimens and long-term safety profiles.