Category: Statistics

Diabetol Metab Syndr. 2025 Apr 15;17(1):127. doi: 10.1186/s13098-025-01696-7.

ABSTRACT

BACKGROUND: Circulating immune cells reportedly affect diabetic neuropathy (DN). Although associations have been previously established between numerous biomarkers and diseases, elucidating their causal relationships remains challenging. Mendelian Randomization (MR) could overcome this difficulty by applying genetic instruments to discern causal links. In this study, we conducted bidirectional two-sample MR to address this problem.

METHODS: We used freely available genome-wide association study summary statistics. We obtained immune cell phenotype-related summary data from a study cohort comprising 3,757 Sardinian individuals that reported data concerning 731 immune cell phenotypes. We obtained DN-related summary data from the FinnGen database and conducted sensitivity analyses. Furthermore, we assessed horizontal pleiotropy using combined MR-Egger and MR-Presso methods. We evaluated heterogeneity using Cochran’s Q test and applied False Discovery Rate correction to the findings.

RESULTS: Our MR analysis significantly associated 24 immune cell phenotypes with DN. Specifically, the presence of CD45 on CD66b + + myeloid cells, HLA DR on CD14 + CD16- monocytes, IgD- CD24- %B cells, and CD27 on IgD- CD38br lymphocytes significantly positively correlated with the risk of DN. In contrast, the presence of CD28- DN (CD4-CD8-) %T cells, FSC-A on HLA DR + T cells, and other four T cell types negatively correlated with DN. Finally, we further confirmed the relationship between different immune cell types and DN.

CONCLUSIONS: We demonstrated the immunological susceptibility of DN and clarified how immune responses influence the course of DN. These findings might help inform immunological therapy techniques as well as novel targets for DN diagnosis and treatment.

PMID:40229883 | DOI:10.1186/s13098-025-01696-7

J Orthop Surg Res. 2025 Apr 15;20(1):376. doi: 10.1186/s13018-025-05795-z.

ABSTRACT

BACKGROUND: Metacarpal neck fractures are common and there are numerous surgical methods available, but each has certain disadvantages and limitations. We modified the conventional Ilizarov external mini-fixator and this study is designed to compare the biomechanical stability of a modified Ilizarov external mini-fixator with conventional fixation methods for metacarpal neck fractures and to provide a basis for its clinical application.

METHODS: Forty fresh porcine metacarpal specimens were used to create metacarpal neck fracture models. The specimens were randomly assigned to four fixation groups (n = 10) as follows: (1) modified Ilizarov external mini-fixator (IEF), (2) retrograde crossed Kirschner wires (KW), (3) antegrade intramedullary Kirschner wires (IK), and (4) locking plate fixation (LP). In the IEF group, the modified design involved crossing two Kirschner wires (K-wires) through the fracture line, with their tails bent twice and connected to the external fixator frame. Biomechanical testing was performed using a modified three-point bending test. Maximum fracture force and bending stiffness were calculated from the force-displacement curves. Kruskal-Wallis test was used to compare statistical differences in maximum fracture force and stiffness among the groups, followed by post hoc pairwise comparisons adjusted with Bonferroni corrections.

RESULTS: The median maximum fracture force values (± interquartile range, IQR) for each group were as follows: IEF 160.3 ± 55.6 N, LP 173.5 ± 42.6 N, KW 91.1 ± 23.1 N, and IK 79.8 ± 37.8 N. The corresponding stiffness values were as follows: IEF 29.5 ± 10.4 N/mm, LP 32.9 ± 10.4 N/mm, KW 17.2 ± 11.3 N/mm, and IK 18.2 ± 13.7 N/mm. The IEF group demonstrated significantly higher maximum fracture force and stiffness than the KW and IK groups; however, no statistically significant differences were observed in the IEF group compared with the LP group.

CONCLUSION: The modified Ilizarov external mini-fixator provided significantly greater biomechanical stability for metacarpal neck fractures than retrograde crossed K-wires and antegrade intramedullary K-wires, achieving comparable performance to the locking plate system. This modified design combines the simplicity and minimally invasive advantages of K-wire fixation with enhanced stability, potentially facilitating early joint mobilization and minimizing the risk of complication.

PMID:40229877 | DOI:10.1186/s13018-025-05795-z

BMC Med Educ. 2025 Apr 14;25(1):528. doi: 10.1186/s12909-025-07112-y.

ABSTRACT

BACKGROUND: Pharmaceutical graduate education often faces a gap between basic theoretical knowledge and the practical realities of drug research, resulting in a limited understanding of new drug development among graduate students. Therefore, it is necessary to implement pharmaceutical education based on the principles and practices of translational medicine to help students gain a deeper understanding of the drug development process and to cultivate professionals capable of translating basic research findings into clinical applications.

METHODS: Pharmaceutical graduate students at Campus A (172 students) were taught using traditional methods, while students at Campus B (203 students) were taught using a reformed approach. The reformed class focused on building an interdisciplinary teaching team, selecting faculty with experience in new drug development and a background in translational medicine, to strengthen the connection between clinical and basic research. Additionally, the course content was designed to reflect the latest advancements in the field, breaking away from traditional textbooks. Various disease models were used to explain the application of translational medicine in pharmacy. The course employed a variety of teaching methods, including theoretical lectures, interactive seminars, case discussions, and expert-led workshops, to enhance students’ understanding of cutting-edge topics and stimulate innovative thinking while addressing real-world clinical issues. Finally, the assessment focused on process-oriented evaluation, using group presentations, literature reviews, and other diverse methods to comprehensively assess both academic and practical abilities.

RESULTS: The comparison of theoretical knowledge exam scores (converted to a percentage scale) between the traditional and reformed class revealed a statistically significant difference (P < 0.05), indicating that students in the reformed class had a better grasp of the theoretical knowledge. In the innovative drug development proposal project, the traditional class consisted of 17 teams, while the reformed class had 20 teams. The independent t-test showed a significant difference in the average scores between the two groups (P < 0.01), suggesting that the reformed class developed stronger drug development strategies based on clinical problems. Furthermore, the results of the student satisfaction survey indicated that students in the reformed class responded positively to the new teaching methods, with only a single-digit number of students reporting dissatisfaction, indicating broad acceptance.

CONCLUSIONS: The reform of the pharmaceutical graduate course “Biopharmaceuticals and Translational Medicine,” based on the principles of translational medicine, not only enhances students’ understanding of the drug development process but also better prepares them for careers in pharmaceutical research and clinical applications.

PMID:40229858 | DOI:10.1186/s12909-025-07112-y

Trials. 2025 Apr 14;26(1):131. doi: 10.1186/s13063-025-08727-8.

ABSTRACT

BACKGROUND: The vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER) trial is a pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical clinical trial of an investigational medicinal product.

METHODS: The original protocol for this trial was published on 31 January 2022 ( https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05966-3 ). This update reports on key changes in the study protocol in version 2.0 which was approved for trial sites from 18 January 2022, and the current version 3.0 which was approved for trial sites from 25 April 2023, and includes current versions of the statistical analysis plan and health economics analysis plan. In summary, there have been changes to three eligibility criteria: removing the word “Actilyse” from exclusion criterion 2, updating exclusion criterion 5 to state abstinence from heterosexual intercourse or the use of highly effective methods of birth control is mandatory for up to 12 weeks after last aflibercept exposure on trial, and clarifying exclusion criterion 6 relating to international normalised ratio (INR) is only applicable to participants receiving warfarin. Changes to secondary outcomes include Radner Reading speed being limited to the study eye only, and moving EQ-5D-5L from a secondary reported efficacy outcome to a component of health economic analysis reporting only. Actilyse Cathflo was added as an additional permitted investigational medicinal product as this is already used in practice in the UK and is molecularly identical to Actilyse 10 mg. Instructions were added to account for participants who had already been exposed to aflibercept or a similar anti-vascular endothelial growth factor (anti-VEGF) within 21 days (the minimum window between anti-VEGF treatments permitted on trial) prior to study enrolment, storage of tissue plasminogen activator in theatre and operating room environments, and the recording of additional, as-needed aflibercept treatments in-between study visits at the discretion of the study investigator. Finally, sections and subsections have been added to detail the imaging analysis plan, patient public involvement plan, INR testing, and recruitment and informed consent components of the trial. The primary analysis of the trial as stated in the statistical analysis plan is the difference between groups in the proportion of participants gaining ≥ 10 ETDRS letters in their study eye at the month 12 visit, whilst the primary health economic analysis of the trial is the difference in quality-adjusted life years between groups at 12 months.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04663750 ; EudraCT: 2020-004917-10.

PMID:40229856 | DOI:10.1186/s13063-025-08727-8

Eur J Med Res. 2025 Apr 15;30(1):285. doi: 10.1186/s40001-025-02558-8.

ABSTRACT

OBJECTIVES: In endoscopic retrograde cholangiopancreatography anesthesia, both intubation and non-intubation techniques have their own advantages and disadvantages. However, whether either approach is associated with postoperative and anesthesia-related adverse events remains controversial.

METHODS: We searched the literature in PubMed, Web of Science, Cochrane Library, Scopus, Ovid and Embase databases up to October 2024. All studies comparing intubated vs. non-intubation anesthesia for endoscopic retrograde cholangiopancreatography were included. The main outcome measures were sedation-related adverse events and death. Data were combined using risk ratio with 95% confidence intervals. The study protocol was prospectively registered with PROSPERO (CRD42024608807).

RESULTS: We finally included 8 studies with a total of 21,433 patients. Endotracheal intubation was associated with a lower risk of sedation-related adverse events (RR: 2.85, 95% CI 1.33-6.09, p = 0.007). However, the risks of death (RR: 0.59, 95% CI 0.36-0.96, p = 0.03) and intraoperative hypotension (RR: 0.43, 95% CI 0.26-0.69, p = 0.0006) were lower without intubation. In the trial-sequence analysis, the trial-sequence monitoring boundary is crossed, indicating conclusive evidence of a statistically significant effect.

CONCLUSIONS: Our findings suggest that endotracheal intubation during endoscopic retrograde cholangiopancreatography is associated with a lower risk of sedation-related adverse events but a higher risk of mortality and intraoperative hypotension compared to non-intubation. However, these associations do not establish direct causality and should be interpreted with caution. Further high-quality randomized controlled trials are needed to validate these findings. Clinicians should adopt a patient-centered approach, carefully balancing the potential benefits and risks of intubation to optimize airway management strategies in endoscopic retrograde cholangiopancreatography.

PMID:40229855 | DOI:10.1186/s40001-025-02558-8

Eur J Med Res. 2025 Apr 15;30(1):283. doi: 10.1186/s40001-025-02548-w.

ABSTRACT

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) has long been recognized as a significant contributor to mortality rates, holding a prominent position in the hierarchy of causes of death. Nevertheless, the presence of a causal relationship between serum uric acid (SUA) and the risk of ASCVD, as well as mortality rates, remains unclear.

METHODS: We initially conducted a comprehensive cohort study utilizing data sourced from National Health and Nutrition Examination Survey (NHANES) 1999-2018 to investigate the specific correlation between SUA levels and ASCVD. Then, we subsequently examined the link between SUA levels and all-cause and cardio-cerebrovascular mortality among ASCVD individuals.

RESULTS: We identified a U-shaped relationship between SUA levels and the risk of ASCVD in all participants (inflection point at 5.399, p value = 0.014). Similarly, SUA levels showed U-shaped trends with all-cause mortality (inflection point at 5.748, p value < 0.0001) and cardio-cerebrovascular mortality (inflection point at 5.936, p value < 0.0001), respectively.

CONCLUSIONS: Our findings demonstrate a U-shaped association between SUA levels and the risks of ASCVD, all-cause mortality, and cardio-cerebrovascular mortality. However, further research is needed to better understand how SUA affects ASCVD and its underlying mechanisms.

PMID:40229850 | DOI:10.1186/s40001-025-02548-w

Eur J Med Res. 2025 Apr 15;30(1):273. doi: 10.1186/s40001-025-02404-x.

ABSTRACT

BACKGROUND: Macular edema (ME) is a prevalent complication of diabetic retinopathy (DR) and retinal vein occlusion (RVO) that contributes significantly to vision impairment worldwide. This condition is primarily driven by elevated vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines, resulting in the use of anti-VEGF agents such as aflibercept and corticosteroids such as dexamethasone implants. However, evidence comparing the clinical efficacy and safety of these two modalities remains limited.

OBJECTIVES: This systematic review and meta-analysis aimed to compare the safety and efficacy of intravitreal aflibercept injections and dexamethasone implants in ME associated with DR and RVO.

METHOD: The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD42024577212). A comprehensive search of the PubMed, Cochrane, Web of Science, and Scopus databases was performed until August 30, 2024. Nine studies, involving 572 eyes, were included in the analysis. Key outcomes assessed included Best-Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT), and Intraocular Pressure (IOP). A random-effects model was applied to the pooled effect size calculations, and heterogeneity was addressed using sensitivity analyses.

RESULTS: Both treatments showed comparable efficacy in improving BCVA and reducing CRT across follow-up intervals. At 3 months, dexamethasone implants demonstrated statistically significant superiority in BCVA improvement (MD = 1.18, 95% CI [0.89, 1.47], P < 0.001) and CRT reduction (MD = – 62.45 µm, 95% CI [- 85.67, – 39.22], P < 0.001) compared to aflibercept. Similarly, at 12 months, dexamethasone implants maintained greater efficacy in CRT reduction (MD = – 58.73 µm, 95% CI [- 78.12, – 39.34], P < 0.001). However, dexamethasone implants were associated with an increased IOP at 3 and 6 months (MD = 1.04 mmHg, 95% CI [0.56, 1.52], P < 0.001). No significant differences in IOP were observed between treatments at 12 months.

CONCLUSION: Intravitreal aflibercept injections and dexamethasone implants are effective modalities for the management of ME, with each presenting distinct advantages. Dexamethasone implants minimize the frequency of treatment, while achieving superior outcomes in terms of BCVA and CRT. However, they are also associated with a heightened risk of IOP elevation and cataract formation. Conversely, aflibercept requires more frequent administration, which may result in logistical and financial challenges for patients and health care providers. Therefore, personalized treatment strategies should consider disease severity, comorbidities, and individual preferences. Future research should prioritize patient-centered outcomes, emphasizing quality of life and treatment costs while also investigating condition-specific responses to these therapeutic interventions.

PMID:40229845 | DOI:10.1186/s40001-025-02404-x

Eur J Med Res. 2025 Apr 15;30(1):287. doi: 10.1186/s40001-025-02550-2.

ABSTRACT

OBJECTIVE: To explore the technical innovation and clinical application effect of inflatable mediastinoscopy synchronous laparoscopic radical resection of esophageal cancer.

METHODS: The clinical data of 180 patients with esophageal cancer treated by the same surgical team from January 2018 to December 2019 were retrospectively analyzed. The patients were divided into the inflatable mediastinoscopy synchronous laparoscopic group (n = 93) and the McKeown group (n = 87) according to the surgical approach. Preoperative general baseline data, perioperative indices, postoperative indices, and short- and long-term survival rates were recorded and statistically analyzed for both groups.

RESULTS: Compared to McKeown’s procedure, the inflatable mediastinoscopy synchronized laparoscopic esophagectomy was associated with relatively less operative time, blood loss, and hospital stay, specifically (94.46 ± 20.17) minutes, (36.76 ± 16.63)ml, and (13.63 ± 2.57) days, respectively. At the same time, the postoperative complication rate of the inflatable mediastinoscopy synchronized laparoscopic esophagectomy was low compared to the postoperative complication rate of McKeown’s procedure.

CONCLUSION: Compared with the traditional McKeown procedure, the patients treated with inflatable mediastinoscopy synchronous laparoscopic radical resection of esophageal cancer have a lower incidence of thoracic complications, shorter operation time, less pain, and faster postoperative recovery so that it can be used as a new supplementary method for mainstream McKeown radical resection of esophageal cancer.

PMID:40229843 | DOI:10.1186/s40001-025-02550-2

J Intensive Care. 2025 Apr 14;13(1):21. doi: 10.1186/s40560-025-00790-2.

ABSTRACT

BACKGROUND: Treatment effect of high-dose intravenous selenium remains controversial in patients with sepsis or septic shock. Here, we reanalyzed data from the randomized placebo-controlled trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT) to reveal possible treatment differences according to established sepsis phenotypes.

METHODS: In this secondary data analysis of the SISPCT trial all 1089 patients of the original study were included. Patients were assigned to one of the four phenotypes by comparing patient variables with the Sepsis Endotyping in Emergency Care (SENECA) validation cohort. Survival analyses were performed using Kaplan-Meier and log-rank tests.

RESULTS: No robust effect of selenium on mortality and other outcome parameters could be determined in any sepsis phenotype. Phenotype frequencies were markedly different in our study cohort compared to previous reports (α: 2.2%, β: 6.3%, γ: 68.0%, δ: 23.4%). Differences in mortality between the respective phenotypes were not significant overall; however, 28-day mortality showed a lower mortality for the α- (20.8%) and β-phenotype (20.3%), followed by the γ- (27.1%), and δ-phenotype (28.5%).

CONCLUSIONS: Application of the four sepsis phenotypes to the SISPCT study cohort showed discrete but non-significant mortality differences within 28 days. However, beneficial treatment effects of high-dose intravenous selenium were still not detectable after categorizing the SISPCT study cohort according to four phenotype criteria.

PMID:40229841 | DOI:10.1186/s40560-025-00790-2

Respir Res. 2025 Apr 14;26(1):146. doi: 10.1186/s12931-025-03214-9.

ABSTRACT

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare and severe form of pulmonary hypertension, with a genetic basis most commonly associated with mutations in the BMPR2 gene. However, no genetic testing has been reported for IPAH patients in the Russian population, nor have systematic studies been conducted to assess the frequency of pathogenic variants in this group.

METHODS: The study cohort included 105 IPAH patients, consisting of 23 males and 82 females, who were managed at the PH care center in Moscow, Russia, from 2014 to 2024. Genetic testing was performed using whole-genome sequencing. Variant identification and annotation were conducted using GATK, DeepVariant, VEP, sv-callers and AnnotSV. A meta-analysis, performed with MOOSE, included 24 studies involving 3124 IPAH patients and 470 P/LP variants. Pathogenicity reassessment was carried out using InterVar, which incorporates ACMG criteria.

RESULTS: Analysis of 105 adult IPAH patients in Russia revealed 11 patients (10.48%) as carriers of pathogenic or likely pathogenetic (P/LP) BMPR2 variants. As the result of reassessment, the number of P/LP BMPR2 variants raised from 394 (59%) to 445 (67%) with 80 pathogenic variants became of uncertain significance, and 152 unclassified variants became P/LP. The meta-analysis of these reevaluated pathogenic variants showed that while the frequency of P/LP variants in our cohort (10.48%) is lower than the overall average of 17.75% from the meta-analysis, the difference is not statistically significant (p = 0.062). Additionally, we report three P/LP BMPR2 variants, not reported in literature, with one being structural, and four P/LP variants in TBX4, ATP13A3 and AQP1 genes from 27 IPAH genes in 3 patients.

CONCLUSIONS: For the first time, we present the results of genetic testing in IPAH patients from the Russian population. Despite the considerable heterogeneity in the world-wide data, the prevalence of pathogenic BMPR2 mutations in IPAH patients from the Russian population does not significantly differ from the overall average in the meta-analysis. It is crucial to periodically reassess the pathogenicity of published variants, as half of the pathogenic BMPR2 IPAH variants were reclassified as LP or of uncertain significance.

PMID:40229839 | DOI:10.1186/s12931-025-03214-9