Therapeutic Advances in Chronic Disease最新文献

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.

Background: Pericardial effusion (PE) is an abnormal fluid volume in the pericardial space and is a common clinical entity. The incidence of PE is estimated diversely and depends on risk factors, etiologies, and geographic locations.

Objectives: This study aimed to assess the clinical characteristics, etiologic spectrum, echocardiographic features, and outcomes among patients with different types of PE.

Method: This retrospective observational study included 93 patients with confirmed PE. Their medical records were reviewed in the hospital information system of Mogadishu Somali Turkish Training and Research Hospital between April 2022 and September 2022. Patient demographics, clinical characteristics, chest X-rays, echocardiography, laboratory findings, management approaches, and outcome reports were reviewed and recorded.

Results: Out of the 3000 participants, 3.1% (n = 93/3000) met the definition of definitive PE. In this study, we included 51 females and 42 males. Among the patients, 86% (n = 80) had at least one comorbidity, with diabetes (38.7%) and hypertension (37.6%) being the most common. The most frequently reported clinical presentation findings were shortness of breath (67.7%), chest pain (49.4%), cough (47.3%), and palpitations (47.3%). Cardiac tamponade developed in 9.7% (n = 9) of the patients. Pericardial taps were performed in 64.5% of the cases. Our analysis showed that the most common cause of PE was cardiac disease (n = 33, 35.4%), followed by tuberculosis (TB) (n = 25, 26.8%), uremic pericarditis (n = 24, 25.8%), and hypothyroidism (n = 10, 10.7%). Regarding the severity of PE based on echocardiographic findings, nearly half of the patients (n = 46, 49.4%) had mild PE, whereas 26.8% (n = 25) had moderate PE, and 23.6% (n = 22) had severe PE. Two-thirds of the cases (66.6%) were managed with furosemide, 48 (51.6%) patients were treated with an anti-inflammatory, hemodialysis was performed in 24 (25.8%) patients and antituberculous medications were administered to 7 (7.5%) patients. Out of the 93 patients, 24 (25.8%) died during the hospital stay. It was determined that the mortality risk of patients with renal failure was 7.518 times higher than those without (p = 0.004), and the risk for those with TB was 5.554 times higher than those without (p = 0.011). Other variables were not influential on mortality (p > 0.050).

Conclusion: Our study results demonstrate the epidemiological profile of PE in Somalia. The leading causes of PE were cardiac diseases, uremic pericarditis, TB, and hypothyroidism. PE is a significant cause of morbidity and mortality in Somalia, especially in individuals with renal failure and TB infection.

The development of a biosimilar is based on comparative structural, physicochemical, functional and clinical assessments. The sum of these analyses encompasses the 'totality of evidence', which demonstrates no clinically meaningful differences between the biosimilar and the reference product (RP). Once biosimilarity has been established, provided there is suitable scientific justification, clinical data may be extrapolated to other indications of the RP. AVT02 has been developed as a biosimilar to high-concentration, low-volume Humira (adalimumab), an anti-tumour necrosis factor-alpha monoclonal antibody approved for various chronic inflammatory indications. The totality of evidence for AVT02 is described, supporting its approval as an adalimumab biosimilar for all approved indications globally. Analytical similarity assessments using mass spectrometry methods demonstrated identical amino acid sequences for AVT02 and the RP, with high similarity in terms of primary structure, post-translational modifications and higher-order structural attributes. The mechanism of action was assessed by various cell-based potency assays and binding assays, and the results demonstrated that AVT02 is highly similar to the RP. No clinically meaningful differences in terms of purity, potency and safety were observed, and minor differences in a few physiochemical attributes did not impact the in vitro biologic activity and were not considered clinically relevant. Clinical similarity was demonstrated by comparing the pharmacokinetic, efficacy, safety and immunogenicity profiles of AVT02 with those of the RP. Clinical studies supported similar pharmacokinetic and comparable immunogenicity profiles between AVT02 and the RP in healthy participants and participants with moderate-to-severe chronic plaque psoriasis, with no new safety signals detected. The totality of evidence described demonstrates the biosimilarity of AVT02 to the RP, thereby fulfilling the scientific and regulatory requirements for AVT02 as a high-concentration biosimilar for the treatment of chronic plaque psoriasis and all approved indications of the RP.

Background: The relationship between short-term cardiac function changes and long-term outcomes in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) remains uncertain, especially when stratified by diabetes status.

Objectives: This study aims to assess the association between short-term cardiac function changes and outcomes such as all-cause mortality and HF hospitalization in patients undergoing CRT, stratified by diabetes status.

Design: This is a cohort longitudinal retrospective study.

Methods: A total of 666 HF patients, treated with CRT between March 2007 and March 2019, were included in this study. Among them, 166 patients (24.9%) were diagnosed with diabetes. Cardiac function was assessed at baseline and again at 6 months, incorporating evaluations of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and QRS duration. The QRS duration represents the time required for a stimulus to spread through the ventricles (ventricular depolarization). The primary endpoints of the study were all-cause mortality and HF-related hospitalization.

Results: During a median follow-up of 2.51 years, 172 (25.8%) patients died and 197 (29.6%) were hospitalized for HF. Changes in LVEF, LVEDD, and LAD within 6 months had similar effects on adverse outcomes in both diabetic and nondiabetic patients. However, the presence of diabetes significantly modified the association between changes in NT-proBNP and QRS duration and adverse outcomes. Short-term changes in NT-proBNP and QRS duration were positively associated with all-cause mortality and HF hospitalization in patients without diabetes. However, the relationship between short-term changes in NT-proBNP and QRS duration and adverse outcomes was non-linear in diabetic patients.

Conclusion: Improvement of cardiac function after CRT implantation can reduce long-term risk of all-cause mortality and HF hospitalization in HF patients. However, the presence of diabetes may affect the association between short-term changes in NT-proBNP and QRS duration and adverse outcomes.

Background: The factors affecting cardiovascular risk associated with vascular calcification in patients with chronic kidney disease are less well addressed. Distinct risk factors may contribute synergistically to this elevated cardiovascular risk in this population.

Objectives: We aimed to determine whether echocardiographic left ventricular hypertrophy (LVH) affects the risk of major adverse cardiac events (MACE) associated with vascular calcification in end-stage kidney disease (ESKD) patients.

Methods: In this retrospective cohort study, ESKD patients underwent chest radiography and echocardiography to assess aortic arch calcification (AoAC) and LVH, respectively, and were classified into three groups accordingly: non-to-mild AoAC without LVH, non-to-mild AoAC with LVH, and moderate-to-severe AoAC. The risks of MACE, cardiovascular mortality, and overall mortality were assessed using Cox proportional hazard analysis.

Results: Of the 283 enrolled ESKD patients, 44 (15.5%) had non-to-mild AoAC without LVH, 117 (41.3%) had non-to-mild AoAC with LVH, and 122 (43.1%) had moderate-to-severe AoAC. After 34.1 months, 107 (37.8%) participants developed MACE, including 6 (13.6%), 40 (34.2%), and 61 (50%) from each respective group. Those with moderate-to-severe AoAC (Hazard ratio, 3.72; 95% confidence interval, 1.58-8.73) had a significantly higher risk of MACE than did those with non-to-mild AoAC without LVH or with non-to-mild AoAC and LVH (Hazard ratio, 2.73; 95% confidence interval, 1.16-6.46). A similar trend was observed for cardiovascular and overall mortality.

Conclusion: Echocardiographic LVH could modify the risk of adverse cardiovascular events associated with vascular calcification in ESKD patients. Interventions aiming to ameliorate both morbidities might be translated into a lower MACE risk in this population.

Background: Recent studies suggest that lipid-lowering agents (LLA) may reduce chronic periodontitis, but it is unknown whether this benefit extends to people with type 2 diabetes (T2D).

Objective: We assessed the association between LLA use and periodontitis in Hispanic adults with T2D.

Design: This was a cross-sectional observational study.

Methods: We assessed the association of LLA use and periodontal parameters in 253 Puerto Ricans 40-65 years with T2D who participated in the Lipid-Lowering agents use in Periodontitis and Diabetes Study study. Participants were classified as (a) none- or <1 year, (b) 1-4 years, or (c) >4 years. The primary outcome consists of a tertile percent of sites with probing pocket depth (PPD) ⩾ 4 mm and the secondary outcome includes tertiles of percent sites with clinical attachment loss (CAL) ⩾ 4 mm. Multinomial logistic regression models adjusted for age, gender, smoking status, education, waist circumference, glycosylated hemoglobin A1C (HbA1c), bleeding on probing, examiner, and anti-inflammatory agents were used to estimate the association.

Results: LLA (92.5%, statins) was used by 52% of participants. LLA use 1-4 years was associated with lower odds of PPD ⩾ 4 mm (OR: 0.22, p = 0.005; high versus low tertile) or lower odds of CAL ⩾ 4 mm (OR: 0.33, p = 0.02, middle versus low tertile), compared to those with LLA minimal or no use. This association was lost for participants who used LLA for >4 years. LLA users for >4 years with periodontal disease had elevated HbA1c (OR: 1.36, p = 0.05).

Conclusion: The use of LLA for 1-4 years was associated with lower values of periodontal parameters versus minimal LLA use. This association was not present among people using LLA > 4 years users, but these participants had poorer glycemic control compared to other participants. In this cross-sectional study, the finding that LLA use 1- 4 years is associated with lower values of periodontal parameters of severity in T2D individuals may help clarify some of the controversies regarding the benefit of these medications in this population.