BMC Medicine最新文献

Background: The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS.

Methods: We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini-Hochberg correction was used to account for multiple comparisons.

Results: Over the median follow-up period of 11.86 years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91-0.99), 0.68 (0.50-0.92), and 0.76 (0.64-0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02-1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45-0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74-0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77 years for cancer mortality outcome, 5034 cancer deaths were detected. An "L-shaped" nonlinear dose-response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77-0.91).

Conclusions: Serum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies.

Background: No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure.

Methods: This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.3 mmol/L) admitted within 72 h from the onset of symptoms. Patients were dichotomised on study day 3 into either target reaching (plasma triglyceride ≤ 5.65 mmol/L) or not. The primary outcome was organ failure-free days (OFFD) to 14 days of enrolment. The association between target-reaching and OFFD was modelled. Additionally, the slope in plasma triglyceride over the first three days in response to treatment was calculated, and its association with OFFD was assessed as a sensitivity analysis.

Results: Among the 300 enrolled patients, 211 underwent exclusive medical treatment, and 89 underwent various blood purification therapies. Triglyceride levels were available in 230 patients on study day 3, among whom 122 (53.0%) had triglyceride levels of ≤ 5.65 mmol/l. The OFFD was not different between these patients and those in whom plasma triglyceride remained > 5.65 mmol/L [median (IQR): 13 (10-14) vs. 14 (10-14), p = 0.46], even after adjustment for potential confounders. For the decline slopes, there was no significant change in OFFD with a steeper decline slope [risk difference, - 0.088, 95% CI, - 0.334 to 0.158, p = 0.48].

Conclusions: Triglyceride-lowering therapies vary greatly across centres. More rapid triglyceride decline was not associated with improving incidence and duration of organ failure.

Background: Long-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity.

Methods: Multicentre cohort study with a collection of both retrospective and prospective data. Demographics, comorbidities, severity and timing of acute COVID, subjective functional status, working activity and presence of 30 different symptoms were collected using a shortened version of the WHO Post COVID-19 Case Report Form. The impact on working activity was assessed in multivariable logistic regression models. Clustering of symptoms was analysed by hierarchical clustering and the clustering of cases by two-step automatic clustering.

Results: The study evaluated 1297 individuals (51.5% women) from 30 clinical centres. Men and women had different profiles in terms of comorbidities, vaccination status, severity and timing of acute SARS-CoV-2 infection. Fatigue (55.9%) and dyspnea (47.2%) were the most frequent symptoms. Women reported more symptoms (3.6 vs. 3.1, p < 0.001), with a significantly higher prevalence of memory loss, difficult concentration, cough, palpitation or tachycardia, dermatological abnormalities, brain fog, headache and visual disturbances. Dyspnea was more common in men. In the cluster analysis of the 19 more common symptoms, five aggregations were found: four two-symptom clusters (smell and taste reduction; anxiety and depressed mood; joint pain or swelling and muscle pain; difficult concentration and memory loss) and one six-symptom cluster (brain fog, equilibrium/gait disturbances, headache, paresthesia, thoracic pain, and palpitations/tachycardia). In a multivariable analysis, headache, dyspnea, difficult concentration, disturbances of equilibrium or gait, visual disturbances and muscular pain were associated with reduced or interrupted working activity. Clustering of cases defined two clusters, with distinct characteristics in terms of phase and severity of acute infection, age, sex, number of comorbidities and symptom profile.

Conclusions: The findings provide further evidence that Long-COVID is a heterogeneous disease with manifestations that differ by sex, phase of the pandemic and severity of acute disease, and support the possibility that multiple pathways lead to different clinical manifestations.

Background: In the United States (US), premature cardiovascular disease (CVD) mortality rates (35-74 years) have exhibited increases in recent years, particularly in younger adults, and large differentials by educational attainment. This trend has occurred concurrently with high and increasing obesity prevalence, which also show significant differences by education. This study aims to jointly model premature CVD mortality trends in the US according to obesity status and educational attainment.

Methods: We used multiple cause of death data from the National Center for Health Statistics, obesity prevalence data from the National Health and Nutrition Examination Survey (NHANES), and educational attainment data from the American Community Survey and NHANES. We applied Bayes' theorem to these data to calculate the conditional probability of premature CVD mortality given obesity status and educational attainment for 2003-2019. We then projected this conditional probability for 2020-2029 using the Lee-Carter model.

Results: The probability of premature CVD mortality was greatest for obesity and low education (not graduated high school) and was substantially higher (females 6.7 times higher, males 5.9) compared with non-obesity and high education (Bachelor's degree or higher) in 2019. There was a widening of the gap in premature CVD mortality from 2003 to 2019 between the obese and non-obese populations, which occurred at each education level and was projected to continue in 2020-2029, especially for males. The conditional probability of premature CVD death for obesity and middle education (finished high school but no Bachelor's degree) increased substantially and was projected to surpass the level for non-obesity and low education in coming years for males and in younger age groups. At high education, the conditional probability of premature CVD death for the obese population was projected to increase to 2029, while for non-obesity it was projected to remain steady for females and fall for males; this projected widening is greatest at older age groups.

Conclusions: The findings demonstrate the public health challenge to reduce premature US CVD mortality posed by continued high obesity prevalence, especially for younger ages, lower education groups and males. The relative importance of obesity in influencing premature CVD mortality trends has risen partly due to the decline in CVD mortality attributable to other risk factors.

Background: Intermittent fasting (IF) holds promise for enhancing metabolic health. However, the optimum IF forms and their superiority over continuous energy restriction (CER) remain unclear due to disconnected findings.

Methods: We systematically searched PubMed, Embase, and the Cochrane databases for meta-analyses of randomized controlled trials (RCTs) investigating the association between IF and metabolic health outcomes. Subsequently, we performed an umbrella review and network meta-analysis (NMA) to evaluate the efficacy of different forms of IF (time-restricted eating (TRE), alternate-day fasting (ADF), and 5:2 diet (regular eating for 5 days and energy restriction for 2 days per week)) compared to CER and usual diets on metabolic health outcomes. To assess the certainty of both direct and indirect estimates, we employed the Confidence in Network Meta-Analysis (CINeMA) approach. Additionally, we calculated the surface under the cumulative ranking curve (SUCRA) for each dietary strategy to determine their ranking in terms of metabolic health benefits.

Results: Ten of the best and non-redundant meta-analysis studies, involving 153 original studies and 9846 participants, were included. When considering direct evidence only, all IF forms significantly reduced body weight compared to usual diets. In NMA incorporating indirect evidence, all IF regimens also significantly reduced body weight compared to usual diets. In the SUCRA of NMA, IF ranked higher than usual diets or CER in 85.4% and 56.1% of the outcomes, respectively. ADF had the highest overall ranking for improving metabolic health (ranked first: 64.3%, ranked second: 14.3%).

Conclusions: Overall, all IF forms demonstrate potentials to improve metabolic health, with ADF appearing to produce better outcomes across investigated outcomes. Further high-quality trials are warranted to confirm the (relative) efficacy of IF on metabolic health.

Trial registration: PROSPERO (record no: CRD42022302690).

Background: Human artificial corneas (HAC) generated by tissue engineering recently demonstrated clinical usefulness in the management of complex corneal diseases. However, the biological mechanisms associated to their regenerative potential need to be elucidated.

Methods: In the present work, we generated HAC using nanostructured fibrin-agarose biomaterials with cultured corneal epithelial and stromal cells, and we compared the structure and histochemical and immunohistochemical profiles of HAC with control native corneas (CTR-C) and limbus (CTR-L) to determine the level of biomimicry of the HAC with these two native organs.

Results: HAC tissues consisted of a stratified epithelium and a cellular stromal substitute. The interface between stroma and epithelium was similar to that of CTR-C, without the finger-shaped palisades of Vogt found in CTR-L, and contained a poorly developed basement membrane as determined by PAS histochemistry. Analysis of the stromal layer revealed that HAC contained significantly lower amounts of extracellular matrix components (collagen, proteoglycans, decorin, keratocan, and lumican) than CTR-C and CTR-L, with all samples being devoid of elastic and reticular fibers. At the epithelial level, HAC were strongly positive for several cytokeratins, although KRT5 was lower in HAC as compared to CTR-C and CTR-L. The expression of crystallin lambda was lower in HAC than in control tissues, whereas crystallin alpha-a was similar in HAC and CTR-C. No differences were found among HAC and controls for the cell-cell junction proteins CX43 and TJP1. When specific markers were analyzed, we found that HAC expression profile of KRT3, KRT19, KRT15, and ΔNp63 was more similar to CTR-L than to CTR-C.

Conclusions: These results suggest that HAC generated in the laboratory could be structurally and functionally more biomimetic to the structure found at the corneal limbus than to the central cornea, and open the door to the use of these artificial tissues in patients with limbal deficiency.

Background: Cognitive fusion MRI-guided targeted biopsy (cTB) has been widely used in the diagnosis of prostate cancer (PCa). However, cTB relies heavily on the operator's experience and confidence in MRI readings. Our objective was to compare the cancer detection rates of MRI artificial intelligence-guided cTB (AI-cTB) and routine cTB and explore the added value of using AI for the guidance of cTB.

Methods: This was a prospective, single-institution randomized controlled trial (RCT) comparing clinically significant PCa (csPCa) and PCa detection rates between AI-cTB and cTB. A total of 380 eligible patients were randomized to the AI-cTB group (n = 191) or the cTB group (n = 189). The AI-cTB group underwent AI-cTB plus systematic biopsy (SB) and the cTB group underwent routine cTB plus SB. The primary outcome was the detection rate of csPCa. The reference standard was the pathological results of the combination of TB (AI-cTB/cTB) and SB. Comparisons of detection rates of csPCa and PCa between groups were performed using the chi-square test or Fisher's exact test.

Results: The overall csPCa and PCa detection rates of the whole inclusion cohort were 58.8% and 61.3%, respectively. The csPCa detection rates of TB combined with SB in the AI-cTB group were significantly greater than those in the cTB group at both the patient level (58.64% vs. 46.56%, p = 0.018) and per-lesion level (61.47% vs. 47.79%, p = 0.004). Compared with cTB, the AI-cTB could detect a greater proportion of patients with csPCa at both the per-patient level (69.39% vs. 49.71%, p < 0.001) and per-lesion level (68.97% vs. 48.57%, p < 0.001). Multivariate logistic analysis indicated that compared with the cTB, the AI-cTB significantly improved the possibility of detecting csPCa (p < 0.001).

Conclusions: AI-cTB effectively improved the csPCa detection rate. This study successfully integrated AI with TB in the routine clinical workflow and provided a research paradigm for prospective AI-integrated clinical studies.

Trial registration: ClinicalTrials.gov, NCT06362291.

Background: The adverse effects of early-life tobacco smoke exposure on chronic kidney disease (CKD) risk remain unclear. This study aimed to investigate the associations of early-life tobacco smoke exposure with CKD incidence in adulthood, and further explore the modification effects of physical activity (PA).

Methods: A total of 352,883 participants were included from the UK Biobank. The information on early-life tobacco smoke exposure was assessed by employing in utero tobacco smoke exposure and age of smoking initiation. Weekly moderate-to-vigorous physical activity (MVPA) was calculated for each individual. Cox proportional hazard regression was fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CKD risk, and to investigate the modification effects of MVPA.

Results: CKD incidence significantly increased in participants with in utero tobacco smoke exposure (HR: 1.08, 95% CI: 1.04, 1.12). Compared with never-smokers, we found a monotonic increase in the risk of CKD with smoking initiation across adulthood (HR: 1.21, 95% CI: 1.16, 1.27), adolescence (HR: 1.29, 95% CI: 1.24, 1.35), and childhood (HR: 1.34, 95% CI: 1.25, 1.43) (P trend < 0.001). Additionally, we identified joint cumulative effects of MVPA and early-life tobacco smoke exposure on incident CKD. Compared with never-smokers with recommended MVPA, prenatal or childhood tobacco smokers without recommended MVPA had the highest CKD risk, and the HRs (95% CIs) were 1.17 (1.10, 1.24) and 1.51 (1.36, 1.68), respectively.

Conclusions: Early-life tobacco smoke exposure may contribute to CKD incidence in adulthood, and the observed associations could be modified by MVPA. These findings provide important information on CKD prevention in the participant's early life while urging a more rapid and powerful need for tobacco control among pregnant couples, children, and adolescents.

Background: The extent to which type 2 diabetes (T2D) reduces life expectancy depends on the risk of complications. We aimed to characterise the relationship between risk factors for diabetes complications and life expectancy, in individuals with T2D, free from major chronic disease, in a regional database linked with national New Zealand health databases.

Methods: A prospective cohort study design was employed, analysing data from individuals with T2D drawn from the comprehensive Diabetes Care Support Service database (1994-2018). Participants with known values for all five within-target risk factors (WTRF +) including blood pressure, glycaemia, and LDL cholesterol, alongside being non-smoking with normal renal function at baseline, were included. Life expectancy free from cardiovascular disease (CVD), cancer, and dementia at age 50 years was estimated using multistate life tables, adjusting for demographics and clinical metrics.

Results: Women and men with no WTRF + at enrolment had a life expectancy free from CVD, cancer, or dementia of 13.1 (95% confidence interval: 9.1-19.0) and 11.2 (6.7-18.6) years, respectively. For the most socioeconomically deprived groups or Māori with no WTRF + at baseline, life expectancies were markedly lower. Life expectancies were 23.7 (18.9-29.7) years for women and 23.2 years (17.2-31.4) years for men with four or five WTRF + at baseline, respectively. While an increasing number of WTRF + at baseline was significantly associated with improved outcomes in men and certain subgroups (e.g. Other ethnicity group), this trend was not statistically significant for women overall or in most subgroups.

Conclusions: Having multiple WTRF + at baseline is associated with a considerable increase in life expectancy free from major chronic disease among individuals with T2D. This highlights the importance of lifestyle and clinical interventions in the management of T2D and in the prevention and management of associated chronic conditions.

Background: Previous observational studies have suggested diabetic patients should synchronize their foods and nutrient intake with their biological rhythm; however, the optimal intake time of coffee and tea for reducing all-cause and disease-specific mortality in diabetes is still unknown. This study aims to examine by investigating the association of timing for coffee and tea consumption with long-term survival in people with diabetes.

Methods: A total of 5378 people with diabetes who enrolled in the National Health and Nutrition Examination Survey from 2003 to 2014 were recruited for this study. Coffee and tea intakes were measured by a 24-h dietary recall, which were divided by different time intervals across the day, including dawn to forenoon, forenoon to noon, noon to evening, and evening to dawn. Weighted cox proportional hazards regression models were developed to evaluate the survival-relationship of coffee and tea consumption with mortality of all-cause, cardiovascular disease (CVD), stroke, and diabetes.

Results: During 47,361 person-year follow up, total 1639 death cases were documented, including 731 CVD deaths, 467 heart disease deaths, 99 stroke deaths, and 462 diabetes deaths. After adjustment for potential confounders, compared with participants without drinking coffee during dawn to forenoon, drinking coffee at this period was associated with increased mortality risk of all-cause (HR 1.25, 95% CI 1.05-1.50), CVD (HR 1.41, 95% CI 1.07-1.86), heart-disease (HR 1.47, 95% CI 1.05-2.07), and diabetes (HR 1.50, 95% CI 1.10-2.04). In contrast, drinking coffee during forenoon to noon had lower mortality risk of all-cause (HR 0.80, 95% CI 0.69-0.92), CVD (HR 0.79, 95% CI 0.63-0.99), and heart disease (HR 0.70, 95% CI 0.52-0.94). Similarly, drinking tea during forenoon to noon had lower risk of CVD mortality (HR = 0.62, 95% CI 0.44-0.87).

Conclusions: This study suggests that drinking coffee in dawn to forenoon is linked to a higher risk of death, but having coffee and tea from forenoon to noon is linked to a lower risk of overall mortality, CVD, and heart disease in individuals with diabetes.