Authors: Yongli Tao, Yuan Gao, Lu Zhao, Yafang Xu, Chenyang Jiang, Kai Liu, Hui Fang, Lulu Pei, Xin Wang, Rui Zhang, Jun Wu, Jing Yang, Xinsheng Han
Abstract:
Background: The benefits of intravenous thrombolysis in patients with acute minor stroke remain controversial.
For the aim of providing a better therapeutic strategy, high-quality trials are.....
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Authors: Yongli Tao, Yuan Gao, Lu Zhao, Yafang Xu, Chenyang Jiang, Kai Liu, Hui Fang, Lulu Pei, Xin Wang, Rui Zhang, Jun Wu, Jing Yang, Xinsheng Han
Background: The benefits of intravenous thrombolysis in patients with acute minor stroke remain controversial.
For the aim of providing a better therapeutic strategy, high-quality trials are required to validate the efficacy of thrombolytic medicine other than intravenous recombinant tissue plasminogen and tenecteplase. In the trial, we evaluate
the efficacy and safety of urokinase (UK) in acute minor stroke.
Methods: This multicenter, open-label, blinded-endpoint, randomized controlled clinical trial enrolled patients
with minor stroke within 6 h of symptom onset, with a NIHSS score ≤ 5. The trial was conducted at 25 hospitals in China
between October 2020 and February 2023. Eligible patients were randomized to the UK group (1,000,000 U) or the best
medicine treatment group. The responsible investigator recommended and implemented the best medicine treatment
based on guidelines. The primary endpoint was an excellent functional outcome, defined as a modified Rankin scale
(mRS) score of 0–1 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 36 h.
Results: A total of 999 patients were enrolled in the trial, the median age was 64 years, 371 (36.9%) were women;
the median (IQR) NIHSS score was 3 (2–4). At 90 days, the primary endpoint was observed in 427 patients (84.9%)
in the UK group and 425 patients (85.7%) in the control group (adjusted risk ratio [RR] 1.00, 95% CI 0.96–1.05, p = 0.87).
A total of 3 patients in the UK-treated (0.6%) group experienced sICH compared to 1 patient (0.2%) in the control
group (RR 1.83, 95% CI 0.16–20.27, p = 0.62).
Conclusions: For patients with acute minor stroke treated within 6 h of symptom onset, UK intravenous thrombolysis
treatment was not found to be beneficial in terms of excellent functional outcome at 90 days, whereas it was safe.
Tao, Y., Gao, Y., Zhao, L. et al. Effect of intravenous urokinase vs best medicine treatment on functional outcome for patients with acute minor stroke (TRUST): a randomized controlled trial. BMC Med23, 6 (2025). https://doi.org/10.1186/s12916-024-03820-2
Authors: Sweta Pathak, Tom G. Richardson, Eleanor Sanderson, Bjørn Olav Åsvold, Laxmi Bhatta and Ben M. Brumpton
Abstract:
Background: Obesity particularly during childhood is considered a global public health crisis and has been linked
with later life health consequences including mental health. However, there.....
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Authors: Sweta Pathak, Tom G. Richardson, Eleanor Sanderson, Bjørn Olav Åsvold, Laxmi Bhatta and Ben M. Brumpton
Background: Obesity particularly during childhood is considered a global public health crisis and has been linked
with later life health consequences including mental health. However, there is lack of causal understanding if childhood body size has a direct effect on mental health or has an indirect effect after accounting for adulthood body size.
Methods: Two-sample Mendelian randomization (MR) was performed to estimate the total effect and direct effect
(accounting for adulthood body size) of childhood body size on anxiety and depression. We used summary statistics
from a genome-wide association study (GWAS) of UK Biobank (n = 453,169) and large-scale consortia of anxiety (Mil
lion Veteran Program) and depression (Psychiatric Genomics Consortium) (n = 175,163 and n = 173,005, respectively).
Results: Univariable MR did not indicate genetically predicted effects of childhood body size with later life anxiety
(beta = − 0.05, 95% CI = − 0.13, 0.02) and depression (OR = 1.06, 95% CI = 0.94, 1.20). However, using multivariable
MR, we observed that the higher body size in childhood reduced the risk of later life anxiety (beta = − 0.19, 95% CI =
− 0.29, − 0.08) and depression (OR = 0.83, 95% CI = 0.71, 0.97) upon accounting for the effect of adulthood body size.
Both univariable and multivariable MR indicated that higher body size in adulthood increased the risk of later life anxiety and depression.
Conclusions: Higher body size in adulthood may increase the risk of anxiety and depression, independent of childhood higher body size. In contrast, higher childhood body size does not appear to be a risk factor for later life anxiety
and depression.
How To Cite this Article
Pathak, S., Richardson, T.G., Sanderson, E. et al. Investigating the causal effects of childhood and adulthood adiposity on later life mental health outcome: a Mendelian randomization study. BMC Med23, 4 (2025). https://doi.org/10.1186/s12916-024-03765-6
Authors: Manman Chen, Qiongjie Zhou, Yuanyuan Li, Qu Lu, Anying Bai, Fangyi Ruan, Yandan Liu, Yu Jiang and Xiaotian Li
Abstract:
Background: Maternal stress is a potential factor affecting fetal growth, but it is unknown whether it directly affects
fetal growth restriction. This study aims to investigate.....
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Authors: Manman Chen, Qiongjie Zhou, Yuanyuan Li, Qu Lu, Anying Bai, Fangyi Ruan, Yandan Liu, Yu Jiang and Xiaotian Li
Background: Maternal stress is a potential factor affecting fetal growth, but it is unknown whether it directly affects
fetal growth restriction. This study aims to investigate the association between pre-pregnancy maternal stress
with small for gestational age (SGA).
Methods: This study used a population-based retrospective cohort analysis to examine the association between pre-pregnancy maternal stress and SGA in offspring. Data were extracted from the National Preconception Health Care
Project (NPHCP), conducted between 2010 and 2012, which encompassed preconception health-related information
from 572,989 individuals across various regions in China. Logistic regression models were used to assess the associations between pre-pregnancy maternal stress variables and the risk of SGA. In addition, Synthetic Minority Over-sampling Technique (SMOTE) and Propensity Scores (PS) methods were used to enhance the model’s ability to the associations between pre-pregnancy maternal stress and SGA.
Results: Pre-pregnancy maternal stress was significantly associated with an increased the risk of SGA in offspring
(OR 1.35, 95% CI 1.20 to 1.51, P < 0.001). Stress related to life and economic factors notably increased the risk of SGA
across different socio-economic conditions, whereas stress related to friends did not show a statistically significant
association (P > 0.05). Specially, individuals with lower socio-economic status that characterized by below high school
education levels (OR = 1.45, 95% CI: 1.23 to 1.70), farmer occupation (OR = 1.33, 95% CI: 1.15 to 1.55, P = 0.002), rural
residence (OR = 1.38, 95% CI: 1.22 to 1.56, P < 0.001), and younger age (under 35 years: OR = 1.35, 95% CI: 1.20 to 1.52,
P < 0.001) were more susceptible to pre-pregnancy maternal stress, increasing their risk of SGA.
Conclusions: Pre-pregnancy maternal stress was positively associated with an increased risk of SGA in offspring. Individuals with lower socio-economic status were more likely to experience pre-pregnancy maternal stress related to life
and economic factors, which in turn contributed to a higher risk of SGA.
How To Cite this Article
Chen, M., Zhou, Q., Li, Y. et al. Association between pre-pregnancy maternal stress and small for gestational age: a population-based retrospective cohort study. BMC Med23, 7 (2025). https://doi.org/10.1186/s12916-024-03837-7
Authors: Can Huang, Yufang Ding, Zhen Chen, Lijun Wu, Wei Wei, Cheng Zhao, Min Yang, Shudian Lin, Qian Wang, Xinping Tian, Jiuliang Zhao, Mengtao Li and Xiaofeng Zeng
Abstract:
Background: Patients with systemic lupus erythematosus (SLE) suffered from an increasing risk of cardiovascular
diseases. In this multi-center prospective study, we aimed to determine the.....
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Authors: Can Huang, Yufang Ding, Zhen Chen, Lijun Wu, Wei Wei, Cheng Zhao, Min Yang, Shudian Lin, Qian Wang, Xinping Tian, Jiuliang Zhao, Mengtao Li and Xiaofeng Zeng
Background: Patients with systemic lupus erythematosus (SLE) suffered from an increasing risk of cardiovascular
diseases. In this multi-center prospective study, we aimed to determine the association between antiphospholipid
antibodies (aPLs) and future atherosclerotic cardiovascular disease (ASCVD) in SLE.
Methods: In total, 1573 SLE patients were recruited based on the Chinese SLE Treatment and Research group (CSTAR)
registry. aPLs profile, including anticardiolipin antibodies (aCL) IgG/IgM, anti-β2 glycoprotein I antibodies (aβ2GPI)
IgG/IgM, and lupus anticoagulant (LA), were measured in each center. Future ASCVD events were defined as new-onset myocardial infarction, stroke, artery revascularization, or cardiovascular death.
Results: Among the 1573 SLE patients, 525 (33.4%) had positive aPLs. LA had the highest prevalence (324 [20.6%]),
followed by aCL IgG (249 [15.8%]), aβ2GPI IgG (199 [12.7%]). 116 (7.37%) patients developed ASCVD during the mean
follow-up of 4.51 ± 2.32 years and 92 patients were aPLs positive. In univariate Cox regression analysis, both aPLs
(HR = 7.81, 95% CI 5.00–12.24, p < 0.001) and traditional risk factors of cardiovascular disease were associated
with future ASCVD events. In multiple Cox regression analysis, aCL IgG (HR = 1.95, 95% CI 1.25–3.00, p = 0.003), aCL IgM
(HR = 1.83, 95% CI 1.03–3.20, p = 0.039), and LA (HR = 5.13, 95% CI 3.23–8.20, p < 0.001) positivity remained associated
with ASCVD; traditional risk factors for ASCVD, including smoking, gender, age and hypertension, also play an independent role in SLE patients. More importantly, Aspirin can reduce ASCVD risk in SLE patients with positive aPLs
(HR = 0.57 95% CI, 0.25–0.93, P = 0.026).
Conclusions: SLE patients with positive aPLs, especially positive aCL IgG/IgM and LA, warrant more care and surveillance of future ASCVD events during follow-up. Aspirin may have a protective effect on future ASCVD.
How To Cite this Article
Huang, C., Ding, Y., Chen, Z. et al. Future atherosclerotic cardiovascular disease in systemic lupus erythematosus based on CSTAR (XXVIII): the effect of different antiphospholipid antibodies isotypes. BMC Med23, 8 (2025). https://doi.org/10.1186/s12916-024-03843-9
Authors: Jeremy R. Burt, Naim Qaqish, Greg Stoddard, Amani Jridi, Parker Sage Anderson, Lacey Woods, Anna Newman, Malorie R. Carter, Reham Ellessy, Jordan Chamberlin and Ismail Kabakus
Abstract:
Background: Lung cancer is a leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises 85% of cases with rising incidence among never-smokers (NS). This.....
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Authors: Jeremy R. Burt, Naim Qaqish, Greg Stoddard, Amani Jridi, Parker Sage Anderson, Lacey Woods, Anna Newman, Malorie R. Carter, Reham Ellessy, Jordan Chamberlin and Ismail Kabakus
Background: Lung cancer is a leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises 85% of cases with rising incidence among never-smokers (NS). This study seeks to compare clinical, imaging,
pathology, and outcomes between NS and ever-smokers (S) NSCLC patients to identify significant differences if any.
Methods: Retrospective cohort study of 155 NSCLC patients (88 S and 67 NS). The main predictor was smoking. Clinical, imaging, and pathology findings were evaluated at initial biopsy for staging. The primary outcome was all-cause
mortality, and the secondary outcome was 12-month progression-free survival.
Results: Imaging: NS and S had similar nodule size (0.81), calcification (> 0.99), and invasion of adjacent structures
(> 0.99) (p values). NS slightly trended to more commonly involve the RLL vs S the RUL (p = 0.11). NS had higher numbers of extrathoracic metastases at initial biopsy for staging (p = 0.055).
Pathology: NS more commonly had adenocarcinoma compared to S, who had equal numbers of adenocarcinoma
and squamous cell carcinoma (p = 0.001). Rates of lymphovascular and pleural invasion were similar (p = 0.84 and 0.28).
Initial staging: NS were more often initially diagnosed with stage IV disease (p = 0.046), positive nodal disease
(p = 0.002), and metastatic disease (p = 0.004).
Outcomes: S had a non-significant trend toward worse 12-month progression-free survival (rate ratio = 1.31, p = 0.31;
HR = 1.33, p = 0.28). NS and S had similar 1-year all-cause mortality (HR = 1.06, p = 0.90). S had nearly double the risk
of all-cause mortality in 5 years (HR = 1.73, p = 0.056) and 10 years (HR = 1.77, p = 0.02). Median survival was 6.6 years
for NS and 3.9 years for S, with NS surviving 2.7 years longer on average (p = 0.045).
Conclusions: CT nodule features were similar in NS and S. NS more often had metastatic adenopathy, distant metastases, and stage IV disease at initial biopsy. Despite similar 12-month progression-free survival and 1-year all-cause
mortality, S had nearly double the risk of mortality in the first 5 and 10 years post-diagnosis.
Trial registration: Retrospectively registered.
How To Cite this Article
Burt, J.R., Qaqish, N., Stoddard, G. et al. Non-small cell lung cancer in ever-smokers vs never-smokers. BMC Med23, 3 (2025). https://doi.org/10.1186/s12916-024-03844-8
Authors: Jeremy R. Burt, Naim Qaqish, Greg Stoddard, Amani Jridi, Parker Sage Anderson, Lacey Woods, Anna Newman, Malorie R. Carter, Reham Ellessy, Jordan Chamberlin and Ismail Kabakus
Account Details mentioned below: For Electronic Fund Transfer: (NEFT/RTGS)
Authors: Zizhao Qi, Miaohan Qiu, Ying Xu, Kai Xu, Haiwei Liu, Xiaozeng Wang, Jing Li, Bin Liu, Shaoliang Chen, Jiyan Chen, Yaling Han and Yi Li
Abstract:
Background: Whether percutaneous coronary intervention (PCI) can improve the long-term prognosis of patients
with stable coronary artery disease (SCAD) in comparison to conservative treatment remains controversial......
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Authors: Zizhao Qi, Miaohan Qiu, Ying Xu, Kai Xu, Haiwei Liu, Xiaozeng Wang, Jing Li, Bin Liu, Shaoliang Chen, Jiyan Chen, Yaling Han and Yi Li
Background: Whether percutaneous coronary intervention (PCI) can improve the long-term prognosis of patients
with stable coronary artery disease (SCAD) in comparison to conservative treatment remains controversial. The
present study sought to evaluate the impacts of initial invasive versus conservative strategy on long-term clinical
outcomes for patients with SCAD stratified by risk scores.
Methods: This was a sub-analysis of the multicenter, observational Optimal antiPlatelet Therapy for Chinese patients
with Coronary Artery Disease (OPT-CAD) study. Clinical outcomes were compared in SCAD patients who initially
received PCI (invasive strategy) or conservative treatment according to risk stratification by OPT-CAD score. The primary outcome was ischemic events at 5 years, composed of cardiac death, myocardial infarction, and ischemic stroke.
Secondary outcomes included all-cause death, Bleeding Academic Research Consortium (BARC) types 2, 3, or 5, and 3
or 5 bleeding.
Results: The conservative group comprised 1767 (58.0%) patients and the invasive group comprised 1278 (42.0%)
patients. Overall, invasive strategy did not reduce the risk of ischemic events compared with conservative strategy
but was associated with an increased risk of BARC 2, 3, or 5 bleeding (adjusted hazard ratio (HR), 1.59; 95% confidence
interval (CI), 1.13–2.26; P = 0.009). Similar results were observed in the low-risk patient subset (N = 2030). While in the moderate-to-high-risk subset (N = 1015), invasive strategy was associated with a reduced risk of ischemic events (HR, 0.67; 95%
CI, 0.48–0.95; P = 0.02) and all-cause death (HR, 0.73; 95% CI, 0.51–1.03; P = 0.07), and with no excessive risk of bleeding.
Conclusions: Invasive strategy could not confer additional clinical benefits in patients with SCAD compared to conservative strategy, except in patients at moderate-to-high risk. The OPT-CAD risk score may be valuable to the guidance of optimal treatment strategy in SCAD patients.
How To Cite this Article
Qi, Z., Qiu, M., Xu, Y. et al. Comparative outcomes of invasive versus conservative strategy in stable coronary artery disease patients: a risk-stratification-based hypothesis-generative study. BMC Med 23, 199 (2025). https://doi.org/10.1186/s12916-025-04020-2
Authors: Pu Miao, Meiping Ying, Ruotong Chen, Yuyu Yang, Yao Ding, Junming Zhu, Jianhua Feng, Jin Wang, Thandar Aung, Shuang Wang and Bo Jin
Abstract:
Background: Malformations of cortical development (MCD) are a group of congenital brain malformation disor
ders commonly associated with pharmacoresistant epilepsy (PRE). While studies often focus on surgery.....
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Authors: Pu Miao, Meiping Ying, Ruotong Chen, Yuyu Yang, Yao Ding, Junming Zhu, Jianhua Feng, Jin Wang, Thandar Aung, Shuang Wang and Bo Jin
Background: Malformations of cortical development (MCD) are a group of congenital brain malformation disor
ders commonly associated with pharmacoresistant epilepsy (PRE). While studies often focus on surgery outcomes,
the pharmacological treatment is still imperative and the odyssey to PRE remains underexplored. We aim to investi
gate the influence of anti-seizure medications (ASMs) on the development of PRE in this specific patient population.
Methods: We retrospectively included a cohort of epilepsy patients with MRI-confirmed MCD due to abnormal
cell proliferation and apoptosis (group I, mainly FCD II), and abnormal neuronal migration (group II, mainly hetero
topia, lissencephaly, and polymicrogyria) from March 2013 to June 2023. The clinical features of group I and group
II were compared. Factors associated with PRE were analyzed. The time to development of PRE with different ASMs
was assessed using Kaplan–Meier survival analysis.
Results: Of 259 enrolled patients with epilepsy and MRI-confirmed MCD (group I, n = 121; group II, n = 138),
73.4% met the criteria for PRE. The median duration of follow-up from seizure onset to the last visit or surgery
was 103 months (IQR 45–174), with group I showing a significantly higher PRE rate than group II (90.1% vs. 58.7%,
p = 0.000). Binomial regression analysis identified the significant predictors of PRE in MCD patients: high pretreatment
seizure frequency (OR = 2.506), group II patients (OR = 0.248), and failure of the first ASM (OR = 5.885). Sodium chan
nel blockers (SCBs) were the most prescribed initial ASMs and demonstrated a higher response rate than other ASMs.
Kaplan–Meier analysis revealed that using SCBs as the first ASM significantly prolongs the time to PRE, with a median
of 72 months for SCB users versus 48 months for non-SCB users.
Conclusions: Our findings indicate a high prevalence of PRE that varies among different subtypes of MCD. Early
appropriate selection of ASMs, particularly SCBs, can significantly delay the time to PRE onset, offering a promising
strategy for managing this complex patient population. Tailoring pharmacological approaches is crucial for optimizing
outcomes, and further research is warranted to optimize treatment strategies
Highlights: (1) High prevalence of PRE in MCD patients, varying by subtype. (2) Early use of SCBs significantly delays PRE onset. (3) Tailored ASMs are essential for improving outcomes in MCD.
How To Cite this Article
Miao, P., Ying, M., Chen, R. et al. The response to anti-seizure medications and the development of pharmacoresistant epilepsy in malformations of cortical development. BMC Med23, 198 (2025). https://doi.org/10.1186/s12916-025-04019-9
Authors: Samuel Hawley, Albert Prats‑Uribe, Gulraj S. Matharu, Antonella Delmestri, Daniel Prieto‑Alhambra, Andrew Judge and Michael R. Whitehouse
Abstract:
Background: Intra‑articular corticosteroid injection (IACI) is an established treatment option for uncontrolled pain
in osteoarthritis. There is a lack of longer‑term follow‑up in most studies of.....
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Authors: Samuel Hawley, Albert Prats‑Uribe, Gulraj S. Matharu, Antonella Delmestri, Daniel Prieto‑Alhambra, Andrew Judge and Michael R. Whitehouse
Background: Intra‑articular corticosteroid injection (IACI) is an established treatment option for uncontrolled pain
in osteoarthritis. There is a lack of longer‑term follow‑up in most studies of the effects of IACI, meaning there is scarcity
of data on the impact of IACI on the subsequent need for joint replacement. Our aim was to assess the effect of IACI
for knee osteoarthritis on the subsequent incidence of knee replacement surgery and on associated post‑operative
outcomes.
Methods We conducted a cohort study of knee osteoarthritis patients registered in the Clinical Practice Research
Datalink (CPRD) GOLD database with an incident diagnosis between 2005 and 2019. Exposure was single or repeated
IACI use, analysed separately. The primary outcome was knee replacement during 1‑year and 5‑year follow‑ups. Sec
ondary outcomes included post‑operative patient‑reported outcome measures and adverse events. Primary analyses
used general practitioner practice preference for IACI as an instrumental variable given this methodology can account
for strong and unmeasured confounding. Secondary analyses used propensity score matching, accounting for meas
ured covariates only.
Results: During 1‑year follow‑up, 1628/33,357 (4.9%) knee osteoarthritis patients underwent knee replacement,
for which single IACI was associated with lower risk, which persisted to 5‑year follow‑up (incidence rate ratio: 0.52
[0.36, 0.77]). Conversely, in secondary propensity score analyses no association was found between IACI use and knee
replacement rate at 1‑year follow‑up, and an estimated increased rate of knee replacement at 5‑year follow‑up. Use
of IACI pre‑joint replacement was not associated with any adverse post‑operative outcomes, for example, 1‑year
complication rates (per 100 person‑years) following knee replacement were 4.6 (3.8, 5.8), 4.0 (2.7, 6.0) and 5.0 (3.1, 8.1)
among patients with no, single and repeat pre‑joint replacement IACI use, respectively.
Conclusions: Findings from our main analysis suggest that short‑term pain reduction following IACI for knee osteo
arthritis may translate to lower rates of knee replacement over 5 years follow‑up, although contradictory associations
How To Cite this Article
Hawley, S., Prats-Uribe, A., Matharu, G.S. et al. Effect of intra-articular corticosteroid injections for knee osteoarthritis on the rates of subsequent knee replacement and post-operative outcomes: a national cohort study of England. BMC Med23, 195 (2025). https://doi.org/10.1186/s12916-025-04000-6
Authors: Chenghui Lu, Xuan Zhou, Chenglong Yang, Xinxiang Jiang, Xin Li, Zefan Huang, Qing Du and Guoyao Tang
Abstract:
Background: The prevalence of burning mouth syndrome (BMS) is approximately 8% in clinical patients; thus,
BMS remains a therapeutic challenge. Photobiomodulation (PBM) and oral cryotherapy (OCT).....
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Authors: Chenghui Lu, Xuan Zhou, Chenglong Yang, Xinxiang Jiang, Xin Li, Zefan Huang, Qing Du and Guoyao Tang
Background: The prevalence of burning mouth syndrome (BMS) is approximately 8% in clinical patients; thus,
BMS remains a therapeutic challenge. Photobiomodulation (PBM) and oral cryotherapy (OCT) have been evaluated
for the treatment of burning pain, but no confirmatory trials have been performed. To evaluate the comparative
effectiveness of PBM combined with OCT at reducing pain and psychological distress compared with PBM alone, OCT
alone, or drug therapy (DT) alone in a cohort of patients with BMS.
Methods: This multi-institutional, single-blinded (assessor-blinded), randomized controlled trial with 4 treatment
groups was conducted at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine and Affiliated Stomatology Hospital of Guilin Medical University from December 12, 2022, to January 24, 2024. Among the 156 patients
assessed for eligibility, 28 were excluded, and 128 patients with a BMS qualified for randomization to 1 of the 4 treatment groups. The participants received 7 treatment sessions of (1) PBM combined with OCT, (2) PBM, (3) OCT, or (4)
DT during a 7-week period. The coprimary outcome measures were changes in visual analogue scale (VAS) scores
and the overall response rate between baseline and 7 weeks of treatment.
Results: After 7 weeks of treatment, the PBM + OCT group achieved a high overall response rate for pain reduction
(81.25%). This difference in pain reduction trends between the groups resulted in a nearly fivefold greater mean
change in the VAS score at the 12-week assessment for the PBM + OCT group than for the DT group (p < 0.0083).
Furthermore, anxiety symptoms were also significantly alleviated by PBM combined with OCT, resulting in a nearly
tenfold greater mean change in the GAD-7 score at the 7-week assessment in the PBM + OCT group than in the DT
group (p < 0.0083). No severe adverse events were reported during the study period.
Conclusions: PBM and OCT combination therapy reduces oral mucosa pain and alleviates anxiety symptoms
in patients with BMS; thus, this combination therapy is expected to become a promising pain management option
for patients with BMS.
Trial registration: Chinese Clinical Trial Registry Identifier: ChiCTR2300074518.
How To Cite this Article
Lu, C., Zhou, X., Yang, C. et al. Efficacy and safety of photobiomodulation combined with oral cryotherapy on oral mucosa pain in patients with burning mouth syndrome: a multi-institutional, randomized, controlled trial. BMC Med23, 196 (2025). https://doi.org/10.1186/s12916-025-04015-z
Authors: Amber L. Kennedy, Richard J. Hiscock, Beverley J. Vollenhoven, Catharyn J. Stern, Lyle C. Gurrin, Tiki Osianlis, Aleah Kink, Susan P. Walker, Jeanie L. Y. Cheong
Abstract:
Background: Use of intracytoplasmic sperm injection (ICSI) continues to increase as the most common mode
of oocyte insemination during in vitro fertilisation (IVF), sometimes in the.....
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Authors: Amber L. Kennedy, Richard J. Hiscock, Beverley J. Vollenhoven, Catharyn J. Stern, Lyle C. Gurrin, Tiki Osianlis, Aleah Kink, Susan P. Walker, Jeanie L. Y. Cheong
Background: Use of intracytoplasmic sperm injection (ICSI) continues to increase as the most common mode
of oocyte insemination during in vitro fertilisation (IVF), sometimes in the absence of clear indications (i.e. male
factor infertility). Several studies suggest an increased risk of congenital abnormalities after ICSI. The association
between the ICSI technique and long-term childhood development remains unclear.
Methods: Our population-based study included singleton infants conceived via IVF and born between 2005
and 2013. The cohort included state-wide linked maternal and childhood administrative data from Victoria, Australia.
The primary exposure was conception via ICSI (without severe male factor infertility), with those born following stand
ard IVF as controls. Childhood development was examined using the Australian Early Development Census (AEDC),
a broad assessment of childhood development across five domains of health and neurodevelopment performed
in Australian schools every triennium at school entry (age 4–6 years). Our primary outcome used a validated global
measure—developmental vulnerability—defined as scoring less than the 10th percentile in two or more of the five
developmental domains (DV2). Causal inference methods were used to analyse observational data in a way that emu
lates a target randomised clinical trial. The adjustment variable set was determined a priori via a modified Delphi
procedure. Given the use of observational data, there were missing data and inherent differences in the covariate pro
f
ile between exposure cohorts. Multiple imputation, bootstrapping and doubly robust inverse probability weighted
regression adjustment modelling was utilised to allow a causal interpretation of results.
Results: Our cohort (N = 3656) included 1489 IVF and 2167 ICSI-conceived children. We found no causal effect of ICSI
on the risk of AEDC-defined developmental vulnerability at school-entry age compared with children conceived
via standard IVF; adjusted risk difference − 1.11% (95% CI − 4.23 to 2.01%) and adjusted risk ratio 0.90 (95% CI 0.68 to 1.21).
Conclusions: Our findings suggest that the use of ICSI in IVF cycles without severe male factor infertility does
not increase the risk of early childhood developmental vulnerability among children in their first year of school. These
f
indings provide important reassurance for current and prospective parents and clinicians alike.
How To Cite this Article
Kennedy, A.L., Hiscock, R.J., Vollenhoven, B.J. et al. School-age outcomes among IVF and ICSI-conceived children: a causal inference analysis using linked population-wide data. BMC Med23, 194 (2025). https://doi.org/10.1186/s12916-025-03963-w
Authors: Amber L. Kennedy, Richard J. Hiscock, Beverley J. Vollenhoven, Catharyn J. Stern, Lyle C. Gurrin, Tiki Osianlis, Aleah Kink, Susan P. Walker, Jeanie L. Y. Cheong
Account Details mentioned below: For Electronic Fund Transfer: (NEFT/RTGS)
Authors: Jan Neelissen, Per Leanderson, Fredrik H. Nyström, Lena Jonasson and Rosanna W. S. Chung
Abstract:
Background: High intake of fruits and vegetables is generally associated with reduced levels of inflammation. In
line with this, plasma levels of carotenoids have shown inverse.....
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Authors: Jan Neelissen, Per Leanderson, Fredrik H. Nyström, Lena Jonasson and Rosanna W. S. Chung
Background: High intake of fruits and vegetables is generally associated with reduced levels of inflammation. In
line with this, plasma levels of carotenoids have shown inverse associations with inflammatory markers, in particular
C-reactive protein (CRP) and leukocyte counts. However, it remains unclear to what extent carotenoids are associated with specific leukocyte subsets or other inflammatory markers. This study systematically assessed the inter-relationships among total and individual carotenoids, circulating leukocyte subsets, and soluble inflammatory markers
in a middle-aged population.
Methods: A subcohort of 1078 subjects, aged 50–64, was recruited from the Swedish CArdioPulmonary bioImage
Study (SCAPIS) cohort. Leukocyte subsets were determined by whole blood flow cytometry. Five major carotenoids,
namely lutein, β-cryptoxanthin, lycopene, α-carotene and β-carotene, and inflammatory markers including CRP,
interleukin (IL)-6 and interleukin-18, matrix metalloproteinase (MMP)-9, and myeloperoxidase (MPO), were measured
in plasma. Nutrient intake was estimated by validated food frequency questionnaires.
Results: Among leukocyte subsets, only granulocytes showed independent and inverse associations with all carotenoids after adjustment. CRP, IL-18, and MMP-9 exhibited similar inverse relationships with most carotenoids. Mediation
analysis revealed that the associations of carotenoids with CRP and MMP-9 were mediated by granulocyte counts.
Lutein and β-cryptoxanthin remained independently associated with MMP-9 after accounting for the mediation
effects of granulocyte counts. No estimated nutrient intake showed comparable associations with leukocyte subsets
or inflammatory markers.
Conclusions: To our knowledge, this is the largest population-based study investigating relationships
between plasma carotenoids, leukocyte subsets, and soluble inflammatory markers. It provides evidence that low
levels of carotenoids in plasma are linked to low-grade chronic inflammation and, furthermore, that this relationship
is mediated by granulocyte numbers.
How To Cite this Article
Neelissen, J., Leanderson, P., Nyström, F.H. et al. Plasma carotenoids are inversely correlated with granulocyte counts and soluble inflammatory markers in a middle-aged population: a cross-sectional study with mediation analysis. BMC Med23, 427 (2025). https://doi.org/10.1186/s12916-025-04266-w
Authors: Laith Yakob, Kasim Allel, Aiman Elragig, Tim Planche, Tendai Mugwagwa, Jennifer C. Moïsi and Holly Yu
Abstract:
Background: Clostridioides difficile infection (CDI) is associated with high morbidity and mortality, emphasising
the need for prophylaxis. The lead vaccine candidate recently demonstrated promising.....
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Authors: Laith Yakob, Kasim Allel, Aiman Elragig, Tim Planche, Tendai Mugwagwa, Jennifer C. Moïsi and Holly Yu
Background: Clostridioides difficile infection (CDI) is associated with high morbidity and mortality, emphasising
the need for prophylaxis. The lead vaccine candidate recently demonstrated promising reductions in medically
attended cases.
Methods Key risk factors for CDI were incorporated into a hospital-level mathematical model used to simulate
the impact of the vaccine on reducing disease burden in England. Model outputs of interest included medically
attended cases, intensive care admissions and deaths associated with CDI, as well as costs and quality-adjusted life
years (QALYs). Hospital costs and costs of years of life lost due to premature mortality averted per vaccine course were
computed for a 10-year time horizon.
Results: The epidemiological model demonstrated considerable benefits to targeting older age groups whereby
vaccinating only those over the age of 74 years old (i.e. 9% of England’s population) more than halved CDI cases
and intensive care unit (ICU) admissions. Simulations also showed that this could be expected to reduce deaths
by almost two-thirds and that around 20% of lives saved would be achieved through indirect benefits, i.e. due
to reduced transmission to unvaccinated as well as vaccinated individuals. Issuing around 5 million vaccine courses
in both the first and second year to protect the eldest, and 0.4 million annual courses thereafter to maintain effective
coverage of all those over 64 years old, can be expected to avert £378 in costs (2023£) and gain 0.046 QALYs per vaccine course by the fourth year of rollout.
Conclusions: Should a safe and efficacious C. difficile vaccine be licensed, it could be positioned very well for providing considerable economical and health benefits. This work guides how these gains could be maximised for England’s
population
How To Cite this Article
Yakob, L., Allel, K., Elragig, A. et al. Age-targeted vaccination for reducing Clostridioides difficile infection in England: a coupled mathematical-economic modelling analysis. BMC Med23, 426 (2025). https://doi.org/10.1186/s12916-025-04265-x
Authors: Huanyu Zhang, Benjamin R. Underwood, Sabina London, Huitong Zhao, Jiazhou Yu, Da Feng and Shanquan Chen
Abstract:
Background: Despite increased attention on dementia, much remains unknown about the integration of clinical
and non-clinical care, particularly regarding long-term social support, a primary source of.....
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Authors: Huanyu Zhang, Benjamin R. Underwood, Sabina London, Huitong Zhao, Jiazhou Yu, Da Feng and Shanquan Chen
Background: Despite increased attention on dementia, much remains unknown about the integration of clinical
and non-clinical care, particularly regarding long-term social support, a primary source of non-clinical care. This study
uniquely examines the effect of receiving a formal dementia diagnosis on the continuity of social support, an understudied transition point in dementia care pathways.
Methods: In this ambidirectional cohort study, we examined ten waves of data from the Health and Retirement
Survey(HRS) for US adults over 50 through 2000–2018. Eligibility was limited to participants with cognitive impairment. The exposure group were people with a confirmed dementia diagnosis (N = 1261), and the control group were
matched by age, sex, race/ethnicity, and survey wave, but without a confirmed diagnosis (N = 12,604). Unmet social
support was defined as reporting physical disability without receiving corresponding social support. Physical disability
was assessed using measures of basic activities of daily living (BADLs) and instrumental activities of daily living (IADLs).
The data were fitted using controlled interrupted time series analysis to explore the continuity of unmet social support before and after a diagnosis.
Results: After dementia diagnosis, adults experienced a significant increase in unmet IADL support needs (coef = 0.10,
95% CI [0.07, 0.13]), particularly for making phone calls (coef = 0.74, 95% CI [0.16, 1.33]). By race/ethnicity, Hispanics
showed a significant rise in unmet BADL support needs (coef = 0.74, 95% CI [0.03, 1.46]), especially for eating assistance (coef = 1.58, 95% CI [0.17, 2.99]). Blacks experienced increased unmet BADL needs in toileting (coef = 1.52, 95%
CI [0.57, 2.47]) and IADL support (coef = 0.09, 95% CI [0.00, 0.17]). Sex disparities were also identified, with females
showing decreased unmet BADL support(coef = − 0.55, 95% CI [− 1.03, − 0.06]) but increased unmet IADL support
(coef = 0.08, 95% CI [0.04, 0.11]), while males experienced increased unmet toileting (coef = 0.78, 95% CI [0.03, 1.53])
and IADLs support (coef = 0.14, 95% CI [0.10, 0.18]).
Conslusions: Our study identifies a disconnect in the care provided to individuals with dementia before and after
their diagnosis. Notably, post-diagnosis, we observed substantial disparities in unmet social support needs across various racial groups. This highlights the need for more cohesive and equitable care strategies in the dementia care
continuum.
How To Cite this Article
Zhang, H., Underwood, B.R., London, S. et al. Discontinuity of social support among US adults with cognitive impairment before and after the confirmed diagnosis of dementia: a matched ambidirectional cohort study. BMC Med 23, 428 (2025). https://doi.org/10.1186/s12916-025-04264-y
Background: This study aimed to investigate the association between depressive symptom severity and sleep disorders in postmenopausal women.
Methods: This observational study included data from 4808 postmenopausal women derived from a nationally representative sample in the USA. Depressive symptom severity was assessed using the Patient Health Questionnaire-9,
while sleep disorders were identified based on self-reported physician diagnoses. Weighted multivariable logistic
regression models were used to analyze the association between depressive symptom severity and sleep disorders,
adjusting for potential confounders. Restricted cubic splines were applied to evaluate possible nonlinear relationships, and subgroup analyses were conducted across key sociodemographic, health, and behavioral factors. Additionally, Lasso regression and logistic regression were used to identify the most influential predictors of sleep disorders.
Supplementary and sensitivity analyses were performed using alternative sleep outcomes and modified depressive
symptom scales to test robustness and item-level overlap.
Results: Depressive symptom severity was positively associated with sleep disorders, demonstrating a dose-response relationship (P for trend < 0.001). Each unit increase in depressive symptom score was associated
with a 10% higher risk of sleep disorders (OR = 1.10, 95% CI: 1.07–1.13). RCS analysis confirmed a linear association (P for nonlinear = 0.4696). Subgroup analyses identified CVD as a significant effect modifier (P for interaction = 0.019), with a stronger association in individuals with CVD (OR = 1.11, 95% CI: 1.09–1.13) compared to those
without (OR = 1.07, 95% CI: 1.03–1.11). Lasso and logistic regression analyses consistently ranked depressive symptoms
as the strongest predictor of sleep disorders. The association remained robust and specific across both supplementary
outcomes and sensitivity models using modified depressive symptom scales.
Conclusions: This study demonstrated a linear dose–response association between depressive symptom severity
and sleep disorders in postmenopausal women, which was further amplified among individuals with CVD. Depressive
symptoms were identified as the most critical predictor, underscoring the importance of mental health in managing sleep health. These findings highlight the need for integrated interventions combining mental health screening,
lifestyle modifications, and community-based care approaches to mitigate the dual burden of depressive symptoms
and sleep disorders in this vulnerable population.
How To Cite this Article
Cui, Y., Du, H. A population-based observational study using statistical modeling to assess the association between depressive symptom severity and sleep disorders in postmenopausal women. BMC Med 23, 424 (2025). https://doi.org/10.1186/s12916-025-04248-y
Background: Faecalibacterium prausnitzii plays a crucial role in ulcerative colitis (UC) remission, but its action mechanism is unknown. Here, we aimed to explore the.....
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Background: Faecalibacterium prausnitzii plays a crucial role in ulcerative colitis (UC) remission, but its action mechanism is unknown. Here, we aimed to explore the potential mechanisms focusing on the interaction of F. prausnitzii
with host immune response and its potential modulation on gut microbiome.
Methods: RNA-seq analysis together with 16S rRNA sequencing and metabolomics were performed in a dextran
sodium sulfate (DSS)-induced colitis mouse model followed by F. prausnitzii gavage. To present evidence of sIgA
involved in the anti-inflammatory effects of F. prausnitzii, we further applied immunoglobulin A (IgA) knockout mice
and secretory IgA (sIgA) depletion mouse models using polymeric immunoglobulin receptor (pIgR) neutralizing
antibody. Colonic immune cells were characterized by flow cytometry. The fecal relative abundance of F. prausnitzii,
inecalcitol, and colonic IgA expression were assessed in UC patients.
Results: F. prausnitzii markedly ameliorated colitis by alleviating intestinal inflammation and barrier dysfunction,
with significantly decreased abundance of pro-inflammatory taxa (Enterococcus, Desulfovibrio, Escherichia-Shigella,
and Enterorhabdus) and increased abundance of Lachnospiraceae NK4A136_group. Functions related to intestinal
immune network for IgA production pathway were up-regulated shown by transcriptomics and KEGG pathway analysis. Increased expression of IgA production associated genes including MHCII-related genes, Aicda, and Tnfrsfl3c were
verified, accompanied by up-regulated colonic IgA and pIgR. The IgA knockout mice and sIgA depletion model weakened the anti-inflammation and microbiota-modulation effects of F. prausnitzii, which was further proved by fecal
microbiota transplantation (FMT). The shift profile of fecal metabolites after F. prausnitzii supplement was characterized by increased production of inecalcitol, which may account for the enhanced IgA response. In a cohort of UC
patients, the relative abundance of F. prausnitzii was decreased and positively correlated with colonic IgA expression
and negatively correlated with disease severity.
Conclusions: F. prausnitzii effectively alleviated colonic inflammation and modulated dysbiosis via enhancing colonic
IgA response, thus showing promise as a UC treatment.
How To Cite this Article
Qin, W., Yin, N., Xu, B. et al. Faecalibacterium prausnitzii enhances intestinal IgA response by host-microbe derived inecalcitol in colitis. BMC Med 23, 425 (2025). https://doi.org/10.1186/s12916-025-04260-2
Authors: Natalia Blay, Xavier Farré, Judith Garcia-Aymerich, Gemma Castaño-Vinyals, Manolis Kogevinas and Rafael de Cid
Abstract:
Background: Long COVID refers to the persistence of symptoms after SARS-CoV-2 infection. While individual comorbidities have been studied, the role of coexisting chronic conditions remains underexplored......
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Authors: Natalia Blay, Xavier Farré, Judith Garcia-Aymerich, Gemma Castaño-Vinyals, Manolis Kogevinas and Rafael de Cid
Background: Long COVID refers to the persistence of symptoms after SARS-CoV-2 infection. While individual comorbidities have been studied, the role of coexisting chronic conditions remains underexplored. This study investigates
whether pre-pandemic disease trajectories—sequential patterns of chronic conditions—modify long COVID risk
and symptom profiles and explores shared genetic susceptibility.
Methods: We analysed 8322 adult participants (58.6% women) from the COVICAT cohort (aged 40–65 at recruitment), followed between 2020 and 2023. Disease trajectories were reconstructed from electronic health records
(2010–2019), focusing on sequences of two chronic conditions found in ≥ 1% of the cohort. We evaluated shared
genetic architecture and polygenic risk scores (PRS) for predictive capacity.
Results: Thirty-eight disease trajectories were associated with increased long COVID risk. These trajectories primarily involved mental and neurological disorders (e.g. depression, anxiety, migraine), respiratory diseases (e.g. asthma,
allergic rhinitis) and cardiometabolic or digestive conditions (e.g. hypertension, lipidaemia, obesity, gastroesophageal
reflux). No significant genetic correlations with long COVID were detected, but polygenic risk scores for two nervous
system and musculoskeletal conditions showed modest associations with increased risk.
Conclusions: Disease trajectories were significantly associated with long COVID, with a sex effect, highlighting
the importance of pre-pandemic disease trajectories. While no strong overall genetic correlations were found, modest
polygenic associations suggest a role for shared susceptibility in nervous system and musculoskeletal disorders. From
a public health perspective, identifying high-risk multimorbid individuals may inform targeted prevention and care
strategies
How To Cite this Article
Blay, N., Farré, X., Garcia-Aymerich, J., Castaño-Vinyals, G., Kogevinas, M., & de Cid, R. (2025). Pre-pandemic disease trajectories and genetic insights into long COVID susceptibility. BMC medicine, 23(1), 590.
Background: Diabetes mellitus increases the risk of developing tuberculosis (TB) and negatively affects TB treatment
outcomes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in glycemic control but.....
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Background: Diabetes mellitus increases the risk of developing tuberculosis (TB) and negatively affects TB treatment
outcomes. Dipeptidyl peptidase-4 (DPP-4) inhibitors are used in glycemic control but can also modulate immune
pathways involved in immune-mediated diseases. Considering the immunoregulatory effects of DPP-4 inhibitors,
this emulated target trial compared the risk of pulmonary TB in users and non-users of DPP-4 inhibitors with type 2
diabetes mellitus (T2DM).
Methods: We identified 328,842 pairs of DPP-4 inhibitor users and non-users from Taiwan’s National Health Insurance Research Database from January 1, 2007, and December 31, 2019. Cox proportional hazard models were used
to determine the risk of new-onset pulmonary TB between the study and control groups.
Results: The follow-up duration was 5.06 years for DPP-4 inhibitor users and 4.05 years for non-users. The incidence
rates of new-onset pulmonary TB were 1.93 and 2.18 cases per 1,000 person-years in DPP-4 inhibitor users and non-users, respectively. Compared with non-users, DPP-4 inhibitor users had a significantly lower risk of developing
pulmonary TB, with an adjusted hazard ratio (aHR) of 0.85 (95% CI: 0.81–0.90). Kaplan–Meier analysis showed a significantly lower cumulative incidence of new-onset pulmonary TB among DPP-4 inhibitor users than non-users (log-rank
test, p < 0.001).
Furthermore, a longer cumulative duration of DPP-4 inhibitor use was associated with a lower risk of pulmonary TB.
Conclusions: In patients with T2DM, the use of DPP-4 inhibitors was associated with a significantly lower risk of developing pulmonary TB compared to non-use. Additionally, a longer cumulative duration of DPP-4 inhibitor may further
reduce the TB risk.
How To Cite this Article
Chen, Y. G., Wei, J. C. C., Yen, F. S., Sung, C. Y., Huang, Y. H., Yu, T. S., ... & Hsu, C. C. (2025). Target trial emulation of DPP-4 Inhibitors in patients with T2DM for pulmonary tuberculosis: a nationwide observational data. BMC medicine, 23(1), 1-13.
Authors: Seraina Netzer, Lea Büchel, Annina E. Büchi and Carole E. Aubert
Abstract:
Background: Hypophosphatemia, defined as low serum phosphate levels, is a frequent yet underrecognized condition associated with significant morbidity. Its etiology ranges from chronic conditions such as.....
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Authors: Seraina Netzer, Lea Büchel, Annina E. Büchi and Carole E. Aubert
Background: Hypophosphatemia, defined as low serum phosphate levels, is a frequent yet underrecognized condition associated with significant morbidity. Its etiology ranges from chronic conditions such as osteomalacia to acute
states such as refeeding syndrome. This review systematically summarizes evidence and guidelines for phosphate
testing and supplementation in adults, aiming to support clinical decision-making.
Methods: We conducted a systematic review following the PRISMA guidelines. Searches of MEDLINE, Embase,
the Cochrane Library, and Google Scholar from inception to September 2024 included reviews, guidelines, and consensus statements addressing phosphate measurement for hypophosphatemia and supplementation in adults outside intensive care settings. Eligibility criteria included English-language publications focused on diagnostic and therapeutic recommendations. Quality assessment was performed using the AGREE II tool, and data were synthesized
across chronic and acute clinical contexts.
Results: Thirty-three publications (11 guidelines, 19 reviews, and 3 consensus statements) were included, with high
heterogeneity in the recommendations. Phosphate measurement to evaluate chronic hypophosphatemia is recommended for persistent musculoskeletal symptoms, osteoporosis evaluation, and rare conditions known to cause
chronic hypophosphatemia, such as X-linked hypophosphatemia and tumor-induced osteomalacia. The post-kidney
transplantation stage requires intensive early monitoring for hypophosphatemia. Recommendations for testing
for drug-induced hypophosphatemia, such as with ferric carboxymaltose, vary. Phosphate measurement to evaluate acute hypophosphatemia is advised in high-risk settings: refeeding syndrome, hyperglycemic hyperosmolar
syndrome, alcoholic ketoacidosis, worsening COPD or asthma exacerbations. Further potential indications for phosphate measurement include certain iron infusions, tenofovir treatment, immediate post-kidney transplantation,
and intensive hemodialysis. Supplementation is indicated for severe or symptomatic cases, with oral therapy preferred
for chronic conditions and intravenous routes for acute, severe hypophosphatemia.
Conclusions: The heterogeneity in the recommendations emphasizes the need for individualized approaches based
on clinical context. While robust evidence supports testing and supplementation under select conditions, gaps
remain regarding optimal dosing and monitoring protocols. Clinicians should consider phosphate testing in high-risk scenarios and follow evidence-based supplementation guidelines tailored to chronic and acute hypophosphatemia.
Future research is needed to unify recommendations and address existing uncertainties.
How To Cite this Article
Netzer, S., Büchel, L., Büchi, A. E., & Aubert, C. E. (2025). Indications for the evaluation and supplementation of hypophosphatemia: an umbrella systematic review of reviews and guidelines. BMC medicine, 23(1), 591.
Authors: Valeria Elahy, Yu‑Han Chiu, Alpa V. Patel, Erika Rees‑Punia, Marjorie L. McCullough, Anita R. Peoples and Ying Wang
Abstract:
Background: Obesity‑related cancers account for 40% of US cancer cases, and their global burden continues to rise.
Cancer prevention guidelines recommend 150–300 min of moderate or.....
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Authors: Valeria Elahy, Yu‑Han Chiu, Alpa V. Patel, Erika Rees‑Punia, Marjorie L. McCullough, Anita R. Peoples and Ying Wang
Background: Obesity‑related cancers account for 40% of US cancer cases, and their global burden continues to rise.
Cancer prevention guidelines recommend 150–300 min of moderate or 75–150 min of vigorous‑intensity activity
per week (7.5–15 MET‑hrs/wk). However, the long‑term causal effect of sustained leisure‑time moderate‑to‑vigorous
intensity physical activity (MVPA) on obesity‑related cancer risk has not been quantified.
Methods: We emulated a target trial using data from 60,958 cancer‑free adults in the Cancer Prevention Study‑II
Nutrition Cohort (2001–2013) to estimate 11‑year risks of obesity‑related cancers under four sustained MVPA strategies: (1) no intervention (observed MVPA); (2) below recommendations (> 0– < 7.5 MET‑hrs/wk); (3) meeting recommendations (7.5–15 MET‑hrs/wk); and (4) exceeding recommendations (> 15 MET‑hrs/wk). MVPA was self‑reported
every 2 years. The parametric g‑formula was used to estimate cancer risk under each strategy among all eligible
participants and stratified by pre‑intervention MVPA (meeting vs. not meeting recommendations 2 years prior
to intervention).
Results: Over a median follow‑up of 11.4 years (IQR 6.9–11.8), 4344 obesity‑related cancers were diagnosed. Under
no intervention, median baseline MVPA was 12.8 MET‑hrs/wk (IQR 4.5–24.5) overall, 20.5 (IQR 15.2–30.8) among those
meeting (n = 38,558), and 4.3 (IQR 1.5–6.2) among those not meeting recommendations pre‑intervention (n = 22,400).
The estimated 11‑year cancer risk under no intervention was 8.2% overall, 8.1% among those meeting, and 8.7%
among those not meeting recommendations pre‑intervention. Compared to no intervention, risk differences were
0.18% (95% CI: 0.05% to 0.37%) for below‑recommendation MVPA, 0.08% (95% CI: − 0.05% to 0.19%) for meeting,
and − 0.18% (95% CI: − 0.44% to 0.01%) for exceeding recommendations. Among those meeting recommendations
pre‑intervention, risk differences were 0.34% (95% CI: 0.11% to 0.65%), 0.09% (95% CI: − 0.06% to 0.26%), and − 0.21%
(95% CI: − 0.45% to − 0.05%), respectively. Among those not meeting recommendations, corresponding risk differences were − 0.02% (95% CI: − 0.31% to 0.27%), − 0.04% (95% CI: − 0.21% to 0.15%), and − 0.10% (95% CI: − 0.38%
to 0.14%).
Conclusions: We estimated that, compared to no intervention, sustaining MVPA volumes below recommendations
may modestly increase obesity‑related cancer risk over 11 years, whereas exceeding recommendations may modestly
reduce risk, particularly among participants already meeting the recommendations prior to intervention.
How To Cite this Article
Elahy, V., Chiu, Y. H., Patel, A. V., Rees-Punia, E., McCullough, M. L., Peoples, A. R., & Wang, Y. (2025). Effectiveness of sustained leisure-time physical activity strategies for obesity-related cancer prevention: an emulated target trial in a prospective US cohort. BMC medicine, 23(1), 580.
Authors: Shuang Wang, Le Xu, Xue Jiao, Xiaoyu Dong, Zhaoyang Zhong, Qianhui Ren, Xiaoxuan Liu, Ming Yuan and Guoyun Wang
Abstract:
Background: Endometriosis (EM) exhibits localised iron overload. However, the contribution of ferroptosis to EM
pathogenesis remains unclear. We investigated how iron overload affects CD8⁺ T cell.....
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Authors: Shuang Wang, Le Xu, Xue Jiao, Xiaoyu Dong, Zhaoyang Zhong, Qianhui Ren, Xiaoxuan Liu, Ming Yuan and Guoyun Wang
Background: Endometriosis (EM) exhibits localised iron overload. However, the contribution of ferroptosis to EM
pathogenesis remains unclear. We investigated how iron overload affects CD8⁺ T cell immune function and the underlying ferroptotic mechanisms.
Methods: We collected eutopic and ectopic endometrial tissues from 57 patients with stage III–IV EM and eutopic
tissues from 31 controls. Iron deposition was assessed by Prussian blue staining; CD8⁺ T cell infiltration by immunohistochemistry; and ferroptosis in CD8⁺ T cells by immunofluorescence and flow cytometry. In vitro and in vivo assays
measured CD8⁺ T cell ferroptosis and endometrial stromal cell apoptosis via flow cytometry. Transwell assays evaluated cell migration. Gene and protein expression were analysed via RT-qPCR and Western Blot. We verified the effect
of iron overload on the growth of lesions in vivo by constructing a mouse EM model. The role of CD8⁺ T cells in EM
progression was tested using a reinfusion model.
Results: In ectopic EM lesions, CD8⁺ T cells were enriched yet functionally impaired, showing increased ferrous iron
accumulation and lipid peroxidation alongside decreased GPX4 expression. In vitro, iron overload reduced CD8⁺ T cell
viability, elevated lipid peroxidation, and induced mitochondrial damage—effects reversed by ferroptosis inhibitors. Iron overload upregulated p53 and downregulated xCT and GPX4; p53 inhibition blocked ferroptosis, indicating a p53-dependent pathway. In vivo EM models confirmed that excess iron compromises CD8⁺ T cell function
and impairs their recruitment to lesion sites.
Conclusions: Iron overload induces p53-mediated inhibition of xCT/GPX4, triggering ferroptosis in CD8⁺ T cells
and leading to their dysfunction. These insights into ferroptosis–CD8⁺ T cell interactions in EM may guide the development of novel immunotherapeutic strategies.
How To Cite this Article
Wang, S., Xu, L., Jiao, X., Dong, X., Zhong, Z., Ren, Q., ... & Wang, G. (2025). Iron overload-induced ferroptosis in CD8+ T cells leads to functional abnormalities that promote endometriosis progression. BMC medicine, 23(1), 588.
Authors: Giulio Francesco Romiti, Bernadette Corica, Davide Antonio Mei, Arnaud Bisson, Giuseppe Boriani, Brian Olshansky, Tze‑Fan Chao, Menno V. Huisman, Marco Proietti
Abstract:
Background: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy,
is an increasing concern in patients with AF. There remains uncertainty regarding how combinations.....
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Authors: Giulio Francesco Romiti, Bernadette Corica, Davide Antonio Mei, Arnaud Bisson, Giuseppe Boriani, Brian Olshansky, Tze‑Fan Chao, Menno V. Huisman, Marco Proietti
Background: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy,
is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes
of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk
of major outcomes.
Methods: From the prospective GLORIA‑AF Registry, we performed a latent class analysis based on 18 diseases,
encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association
between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome
was the composite of all‑cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed.
Results: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes:
(i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv)
thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants
was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity
phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49–2.09] and 1.57 [1.35–1.81], respectively); similar
results were observed for beta‑blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity
groups (hazard ratio and 95%CI: 1.37 [1.13–1.67] and 1.47 [1.24–1.75], respectively).
Conclusions: Comorbidities influence management and long‑term prognosis of patients with AF. Patients with com
plex phenotypes may require comprehensive and holistic approaches to improve their prognosis.
How To Cite this Article
Romiti, G.F., Corica, B., Mei, D.A. et al. Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry. BMC Med22, 151 (2024). https://doi.org/10.1186/s12916-024-03373-4
Authors: Giulio Francesco Romiti, Bernadette Corica, Davide Antonio Mei, Arnaud Bisson, Giuseppe Boriani, Brian Olshansky, Tze‑Fan Chao, Menno V. Huisman, Marco Proietti
Account Details mentioned below: For Electronic Fund Transfer: (NEFT/RTGS)
Authors: Chunfeng Dai, Muyin Liu, Zheng Yang, Youran Li, You Zhou, Danbo Lu, Yan Xia, Ao Chen, Chenguang Li, Hao Lu, Yuxiang Dai, Jianying Ma, Zhangwei Chen
Abstract:
Background: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched
by our cardiac center examined the performance of indobufen.....
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Authors: Chunfeng Dai, Muyin Liu, Zheng Yang, Youran Li, You Zhou, Danbo Lu, Yan Xia, Ao Chen, Chenguang Li, Hao Lu, Yuxiang Dai, Jianying Ma, Zhangwei Chen
Background: Indobufen is widely used in patients with aspirin intolerance in East Asia. The OPTION trial launched
by our cardiac center examined the performance of indobufen based dual antiplatelet therapy (DAPT) after per
cutaneous coronary intervention (PCI). However, the vast majority of patients with acute coronary syndrome (ACS)
and aspirin intolerance were excluded. We aimed to explore this question in a real-world population.
Methods: Patients enrolled in the ASPIRATION registry were grouped according to the DAPT strategy that they
received after PCI. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE)
and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding. Propensity score matching (PSM)
was adopted for confounder adjustment.
Results: A total of 7135 patients were reviewed. After one-year follow-up, the indobufen group was associated
with the same risk of MACCE versus the aspirin group after PSM (6.5% vs. 6.5%, hazard ratio [HR] = 0.99, 95% confi
dence interval [CI] = 0.65 to 1.52, P = 0.978). However, BARC type 2, 3, or 5 bleeding was significantly reduced (3.0% vs.
11.9%, HR = 0.24, 95% CI = 0.15 to 0.40, P < 0.001). These results were generally consistent across different subgroups
including aspirin intolerance, except that indobufen appeared to increase the risk of MACCE in patients with ACS.
Conclusions: Indobufen shared the same risk of MACCE but a lower risk of bleeding after PCI versus aspirin
from a real-world perspective. Due to the observational nature of the current analysis, future studies are still warranted
to further evaluate the efficacy of indobufen based DAPT, especially in patients with ACS.
Dai, C., Liu, M., Yang, Z. et al. Real-world performance of indobufen versus aspirin after percutaneous coronary intervention: insights from the ASPIRATION registry. BMC Med 22, 148 (2024). https://doi.org/10.1186/s12916-024-03374-3
Authors: Xiao Zhang, Yuyanan Zhang, Hao Yan, Hao Yu, Dai Zhang, Venkata S. Mattay, Hao Yang Tan and Weihua Yue
Abstract:
Background: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric
disorders, possibly through memory processing and neural response to emotional stimuli. Genetic.....
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Authors: Xiao Zhang, Yuyanan Zhang, Hao Yan, Hao Yu, Dai Zhang, Venkata S. Mattay, Hao Yang Tan and Weihua Yue
Background: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric
disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may
not only influence individuals’ choices of residence but also modulate how the living environment affects responses
to episodic memory.
Methods: We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing
between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after
age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity
on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving
the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand
the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced
by early-life urban or rural environments.
Results: Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban
and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023).
For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding
and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli
in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type
2 (NTRK2) (right striatum: P = 1.58×10−6). These findings were confirmed in the replication sample.
Conclusions: We suggest that this differential striatal processing of aversive stimuli observed in individuals
with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits,
heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural
processes in the striatum may play a role in these processes.
How To Cite this Article
Zhang, X., Zhang, Y., Yan, H. et al. Childhood urbanicity is associated with emotional episodic memory-related striatal function and common variation in NTRK2. BMC Med22, 146 (2024). https://doi.org/10.1186/s12916-024-03365-4
Authors: Feihang Wang, Danyang Zhao, Wang‑yang Xu, Yiying Liu, Huiyi Sun Shanshan Lu, Yuan Ji, Jingjing Jiang, Yi Chen, Qiye He, Chengxiang Gong, Rui Liu, Zhixi Su, Yi Dong
Abstract:
Background: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic.....
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Authors: Feihang Wang, Danyang Zhao, Wang‑yang Xu, Yiying Liu, Huiyi Sun Shanshan Lu, Yuan Ji, Jingjing Jiang, Yi Chen, Qiye He, Chengxiang Gong, Rui Liu, Zhixi Su, Yi Dong
Background: Thyroid nodule (TN) patients in China are subject to overdiagnosis and overtreatment. The implementation of existing technologies such as thyroid ultrasonography has indeed contributed to the improved diagnostic accuracy of TNs. However, a significant issue persists, where many patients undergo unnecessary biopsies,
and patients with malignant thyroid nodules (MTNs) are advised to undergo surgery therapy.
Methods: This study included a total of 293 patients diagnosed with TNs. Differential methylation haplotype blocks
(MHBs) in blood leukocytes between MTNs and benign thyroid nodules (BTNs) were detected using reduced representation bisulfite sequencing (RRBS). Subsequently, an artificial intelligence blood leukocyte DNA methylation
(BLDM) model was designed to optimize the management and treatment of patients with TNs for more effective
outcomes.
Results: The DNA methylation profiles of peripheral blood leukocytes exhibited distinctions between MTNs and BTNs.
The BLDM model we developed for diagnosing TNs achieved an area under the curve (AUC) of 0.858 in the validation cohort and 0.863 in the independent test cohort. Its specificity reached 90.91% and 88.68% in the validation
and independent test cohorts, respectively, outperforming the specificity of ultrasonography (43.64% in the validation
cohort and 47.17% in the independent test cohort), albeit with a slightly lower sensitivity (83.33% in the validation
cohort and 82.86% in the independent test cohort) compared to ultrasonography (97.62% in the validation cohort
and 100.00% in the independent test cohort). The BLDM model could correctly identify 89.83% patients whose
nodules were suspected malignant by ultrasonography but finally histological benign. In micronodules, the model
displayed higher specificity (93.33% in the validation cohort and 92.00% in the independent test cohort) and accuracy (88.24% in the validation cohort and 87.50% in the independent test cohort) for diagnosing TNs. This performance
surpassed the specificity and accuracy observed with ultrasonography. A TN diagnostic and treatment framework
that prioritizes patients is provided, with fine‑needle aspiration (FNA) biopsy performed only on patients with indications of MTNs in both BLDM and ultrasonography results, thus avoiding unnecessary biopsies.
Conclusions: This is the first study to demonstrate the potential of non‑invasive blood leukocytes in diagnosing TNs,
thereby making TN diagnosis and treatment more efficient in China.
How To Cite this Article
Wang, F., Zhao, D., Xu, Wy. et al. Blood leukocytes as a non-invasive diagnostic tool for thyroid nodules: a prospective cohort study. BMC Med22, 147 (2024). https://doi.org/10.1186/s12916-024-03368-1
Authors: Chunhu Shi, Jo Dumville, Fernando Rubinstein, Gill Norman, Akbar Ullah, Saima Bashir, Peter Bower and Emma R. L. C. Vardy
Abstract:
Background: Technology-enabled inpatient-level care at home services, such as virtual wards and hospital at home,
are being rapidly implemented. This is the first systematic review to link the components.....
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Authors: Chunhu Shi, Jo Dumville, Fernando Rubinstein, Gill Norman, Akbar Ullah, Saima Bashir, Peter Bower and Emma R. L. C. Vardy
Background: Technology-enabled inpatient-level care at home services, such as virtual wards and hospital at home,
are being rapidly implemented. This is the first systematic review to link the components of these service delivery
innovations to evidence of effectiveness to explore implications for practice and research.
Methods: For this review (registered here https://osf.io/je39y), we searched Cochrane-recommended multiple
databases up to 30 November 2022 and additional resources for randomised and non-randomised studies that com
pared technology-enabled inpatient-level care at home with hospital-based inpatient care. We classified interventions into care model groups using three key components: clinical activities, workforce, and technology. We synthesised evidence by these groups quantitatively or narratively for mortality, hospital readmissions, cost-effectiveness
and length of stay.
Results: We include 69 studies: 38 randomised studies (6413 participants; largely judged as low or unclear risk of bias)
and 31 non-randomised studies (31,950 participants; largely judged at serious or critical risk of bias). The 69 studies
described 63 interventions which formed eight model groups. Most models, regardless of using low- or high-intensity
technology, may have similar or reduced hospital readmission risk compared with hospital-based inpatient care
(low-certainty evidence from randomised trials). For mortality, most models had uncertain or unavailable evidence.
Two exceptions were low technology-enabled models that involve hospital- and community-based profession
als, they may have similar mortality risk compared with hospital-based inpatient care (low- or moderate-certainty
evidence from randomised trials). Cost-effectiveness evidence is unavailable for high technology-enabled models,
but sparse evidence suggests the low technology-enabled multidisciplinary care delivered by hospital-based teams
appears more cost-effective than hospital-based care for those with chronic obstructive pulmonary disease (COPD)
exacerbations.
Conclusions: Low-certainty evidence suggests that none of technology-enabled care at home models we explored
put people at higher risk of readmission compared with hospital-based care. Where limited evidence on mortality
is available, there appears to be no additional risk of mortality due to use of technology-enabled at home models. It is unclear whether inpatient-level care at home using higher levels of technology confers additional benefits. Further
research should focus on clearly defined interventions in high-priority populations and include comparative cost-effectiveness evaluation.
Trial registration: https://osf.io/je39y.
How To Cite this Article
Shi, C., Dumville, J., Rubinstein, F. et al. Inpatient-level care at home delivered by virtual wards and hospital at home: a systematic review and meta-analysis of complex interventions and their components. BMC Med 22, 145 (2024). https://doi.org/10.1186/s12916-024-03312-3
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