Tag: pubmed

Graefes Arch Clin Exp Ophthalmol. 2025 Aug 5. doi: 10.1007/s00417-025-06880-z. Online ahead of print.

ABSTRACT

This systematic review and meta-analysis aims to evaluate the efficacy of suprachoroidal triamcinolone acetonide (SCTA) in patients with diabetic macular edema (DME). The study was conducted following PRISMA guidelines, involving a comprehensive search of electronic databases was performed to identify relevant studies assessing SCTA in DME, and data from selected studies were pooled for analysis. The primary outcomes were changes in central macular thickness (CMT) and corrected distance visual acuity (CDVA). Secondary outcome was the duration of therapeutic effect, intraocular pressure (IOP) and other complications. The random-effects model was used to calculate the pooled mean with 95% confidence intervals (CIs). Eleven studies were included, comprising a total sample size of 411 eyes. In patients with DME receiving SCTA, CMT significantly improved over the study period (SMD: -5.377, 95% CI: -7.290 to -3.464, P = 0.000), decreasing from a pooled mean of 545.313 μm at baseline to 315.794 μm at last follow-up post-injection. CDVA improved from a baseline value of 0.777 to 0.521 LogMAR at final follow-up but failed to demonstrate statistical significance (SMD: 1.083, 95% CI: -0.520 to 2.686, P = 0.185). Additionally, the therapeutic effect of SCTA was shown to last up to 6 to 12 months in several studies. Post-injection IOP remained stable (SMD: 0.428, 95% CI: -0.324 to 1.179, P = 0.264). Other complications included cataract progression, particularly in phakic patients, while retinal detachment and endophthalmitis were rare. In conclusion, SCTA intervention in DME patients demonstrated a significant improvement in CMT along with stable CDVA and IOP. The absence of IOP elevation is a key advantage, making SCTA an effective and safe treatment option with favorable structural and visual outcomes.

PMID:40762816 | DOI:10.1007/s00417-025-06880-z

Clin Genet. 2025 Aug 5. doi: 10.1111/cge.70038. Online ahead of print.

ABSTRACT

Avascular necrosis (AVN) and minimal trauma fractures (MTF) cause significant morbidity in patients with telomere biology disorders (TBDs). TBDs are associated with very high risks of bone marrow failure, pulmonary fibrosis, cancer, and many other complications due to pathogenic germline variants in genes essential for telomere function and maintenance. To understand the extent to which AVN and MTF occur in TBDs and identify areas requiring more research in the role of telomeres in bone biology. We assessed the occurrence of AVN and MTF in 233 patients with TBDs. An age, gender, and gene-matched TBD patient control group was used to assess associations between AVN/MTF and clinical characteristics. Forty-two (18%) patients with TBD developed at least one AVN and/or MTF event with 19 patients experiencing their first event in childhood. AVN and MTF were most common in patients with autosomal or X-linked recessive, or heterozygous TINF2 disease (19/36 AVN and 17/19 MTF). Androgen and corticosteroid use were more common in patients with AVN compared with matched patient controls (41.2% vs. 16.3%, p < 0.05 and 41.2% vs. 14%, p < 0.01, respectively); however, 57.1% of patients experienced AVN and/or MTF events in the absence of androgen or corticosteroid use. Severe bone marrow failure and hematopoietic cell transplantation history were significantly more common in MTF patients than in controls (44.2% and 30.2% respectively, p < 0.05). There were no statistically significant associations between low bone mineral density or vitamin D deficiency and AVN or MTF. AVN and MTFs are common, debilitating complications in TBDs and frequently occur independently of androgen or corticosteroid use. Our results underscore the need for disease-specific translational studies as well as improved prevention and therapeutic options for patients with TBDs. Trial Registration: ClinicalTrials.gov identifier: NCT00027274.

PMID:40762130 | DOI:10.1111/cge.70038

Knee Surg Sports Traumatol Arthrosc. 2025 Aug 5. doi: 10.1002/ksa.12812. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to quantify the contribution of the meniscofemoral ligaments (MFLs) on restraining a posterior tibial translation (PTT) in the human knee joint.

METHODS: Sixteen human cadaveric knee joints were tested in a robotic test setup with six degrees of freedom. Knees with no MFL, one MFL and two MFLs were included. Knee joints without MFLs were excluded from the statistical analysis regarding the influence of MFLs on PTT. The knees were tested in a displacement-controlled protocol, which replayed the native kinematics of a force controlled test protocol with PTT at 89 N in neutral tibial rotation, PTT in 5 Nm internal rotation, PTT in 5 Nm external rotation, while constantly measuring the force. The principle of superposition was used to determine the contribution of each cut structure (in-situ forces) to restraint of the performed movements. First, the anterior and posterior MFL (aMFL/pMFL) were randomly cut, followed by the posterior cruciate ligament (PCL).

RESULTS: Neither the aMFL, nor the pMFL showed a significant contribution to the restriction of PTT in the PCL-intact knee neither in 0°, 30°, 60° or 90° of flexion in neutral, internal, or external rotation (p > 0.05). The PCL showed a significant contribution to the knee joint restraining PTT in 0°, 30°, 60° and 90° flexion as well as in all rotation states (all p < 0.05). A contribution of the PCL restraining PTT of 28% ± 14% in 0° flexion, 53% ± 21% in 30° flexion, 61% ± 20% in 60° flexion and 54% ± 16% in 90° knee flexion was measured in neutral rotation.

CONCLUSION: The MFLs do not contribute to restriction of a PTT in any flexion angle, while the PCL acts as the primary restraint against PTT from 0°-90° knee flexion. This effect was seen in neutral rotation as well as in tibial internal and external rotation. This study indicates that a dissection of the MFLs to gain access to the PCL during reconstruction surgery does not destabilise the knee.

LEVEL OF EVIDENCE: Level N/A.

PMID:40762113 | DOI:10.1002/ksa.12812

Acta Orthop. 2025 Aug 5;96:587-594. doi: 10.2340/17453674.2025.44250.

ABSTRACT

BACKGROUND AND PURPOSE: Arthroplasty registries report revision risk, but patient-reported outcomes may also measure implant performance. We aimed to evaluate (i) change in patient-reported outcome measures (PROMs) across multiple total knee arthroplasty (TKA) designs in a regional registry, (ii) the association of patellar resurfacing on the change in PROMs, and (iii) the variation in PROMs change within implants with or without patellar resurfacing.

METHODS: This is a cohort of primary TKAs from Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) performed between January 1, 2017 and September 30, 2021. The dependent measure was change in KOOS JR. Independent variables were implant name and patellar resurfacing. Multivariate modeling adjusted for patient-level factors. A previous report suggests a change of 23 points in KOOS JR as clinically relevant in achieving acceptable pain/function levels. A clinically relevance ratio (CRR) of those achieving the threshold of 23 points to the overall group was calculated for each implant.

RESULTS: 18 implant designs met the inclusion criteria. There were 51,606 cases with complete preoperative and postoperative KOOS JR matched pairs. There was variation in improvement from preoperative to postoperative unadjusted KOOS JR scores across implant designs (P < 0.001), ranging from 18.7 (95% confidence interval [CI] 16.8-20.6) to 27.0 (CI 24.9-29.2). Patellar resurfacing resulted in greater KOOS JR improvement 1.0 (CI 0.5-1.5, P < 0.001). Of the cases with resurfaced patellae, the CRR was 50.2% (CI 49.7-50.7). For cases without resurfaced patellae, the CRR was 47.2% (CI 45.9-48.5). The association of implant design persisted whether the patella was resurfaced or not, evident in the adjusted mean change in KOOS JR (P < 0.001), ranging from 20.1 (CI 17.6-22.6) to 25.5 (CI 24.3-26.7) for resurfaced and from 17.0 (CI 13.9-20.1) to 23.3 (CI 20.3-26.2) for not resurfaced, and the CRR difference (P < 0.001), ranging from 45.8% (CI 42.5-48.6) to 55.8% (CI 50.4-60.8) for resurfaced and from 37.9% (CI 27.4-44.7) to 51.4% (CI 43.9-56.6) for not resurfaced.

CONCLUSION: Implant design and patellar resurfacing both show an association with KOOS JR improvement. Variations in implant design persist whether the patella is resurfaced or not. Implant selection and patellar resurfacing may be associated with patient outcomes.

PMID:40762095 | DOI:10.2340/17453674.2025.44250

Anal Chem. 2025 Aug 5. doi: 10.1021/acs.analchem.5c01257. Online ahead of print.

ABSTRACT

Pathological processes are often accompanied by alterations of protein conformations in blood serum, making investigation of these structural rearrangements highly relevant for clinical diagnostics. Conformation of albumin, the predominant protein in blood serum, is known to be a sensor of pathologies in the human organism; however, label-free methods for its assessment directly in blood serum samples are lacking. In this work, we present a novel analytical methodology for evaluating albumin conformation using the fluorescence parameters of intrinsic blood serum fluorophores excited in the visible range. We first estimate the contribution of various endogenous fluorophores excited in the vicinity of 400 nm to both steady-state fluorescence and fluorescence decay across picosecond and nanosecond time scales, showing that one of the dominant fluorophores is bilirubin, an albumin ligand. In model experiments, we then demonstrate that the structural and photophysical features of bilirubin make its fluorescence decay at picosecond time scale sensitive to conformation of the protein-bilirubin complex. As a final step, it is demonstrated that changes in the ultrafast fluorescence decay parameters of the bilirubin are sensitive enough to detect biologically relevant differences in albumin conformation in serum across different patients. Specifically, we observed statistically significant differences in blood serum albumin’s conformation for patients of different age groups (≤34 years and ≥65 years), suggesting that bilirubin may serve as a promising intrinsic sensor for assessing albumin conformational modifications in blood serum.

PMID:40762091 | DOI:10.1021/acs.analchem.5c01257

J Sep Sci. 2025 Aug;48(8):e70233. doi: 10.1002/jssc.70233.

ABSTRACT

Plantaginis semen (PS), a traditional herbal medicine extensively utilized in China, contains bioactive compounds that exhibit notable therapeutic effects in promoting diuresis, regulating blood pressure, modulating lipid metabolism, and controlling blood glucose levels. Crude PS (CPS) and salt-processed CPS (SPS) are the two most commonly used decoction pieces of PS. The therapeutic efficacy of PS is further enhanced after salt processing, resulting in the SPS exhibiting superior pharmacological effects compared to the CPS. This study aims to explore the differences in chemical constituents between CPS and SPS in vitro. Additionally, the study seeks to compare the pharmacokinetics (PKs) of bioactive compounds after oral administration of extracts from both crude and salt-processed PS in rats. The identification results showed that there were 45 common components and six unique components between CPS extract and SPS extract. The results of multivariate statistical analysis have identified six differential components. The PK study results demonstrated that the mean plasma concentration-time profile and PK parameters of six representative components were significantly different between CPS extract and SPS extract. This study proved that salt-processed method increased the dissolution of most components and absorption of active components in PS, and revealed the material basis underlying the superior efficacy of SPS compared to CPS to some extent. This study provides a scientific foundation for the enhanced therapeutic efficacy of traditional Chinese medicine (TCM) following salt processing, elucidating how this ancient preparation method amplifies pharmacological activity through modern mechanistic insights.

PMID:40762073 | DOI:10.1002/jssc.70233

SAR QSAR Environ Res. 2025 Aug 5:1-28. doi: 10.1080/1062936X.2025.2535606. Online ahead of print.

ABSTRACT

The existing QSAR approaches for mammalian acute toxicity have been limited in scope, often relying on small or narrowly focused datasets and on classification endpoints. In contrast, our work leverages a sufficiently large curated dataset (9843 rat oral and 2323 intravenous LD₅₀ values) to build regression models of acute toxicity. The best-performing QSAR models developed using 2D RDKit descriptors and the Cat Boost method achieve Q² _test = 0.66 at a data coverage of at least 77% within the applicability domain (AD) during validation of test sets. All models were rigorously validated according to OECD QSAR principles with clearly defined endpoints, explicit algorithms, and a well-characterized AD. The best QSAR models are integrated into the ToxAI_assistant web platform (https://tox-ai-assistant.streamlit.app/), which includes toxicity-level prediction with allowance for AD in terms of World Health Organization (WHO). We also provide mechanistic insight by identifying key toxicophores – substructural features statistically associated with high toxicity – thereby offering a structural interpretation. In sum, these elements (large and diverse data, regression modelling, WHO-based categorization, detailed fragment analysis, and AD assessment) together address the gaps of earlier studies and constitute the core novelty of our approach.

PMID:40762068 | DOI:10.1080/1062936X.2025.2535606

Photobiomodul Photomed Laser Surg. 2025 Aug 5. doi: 10.1177/15578550251364114. Online ahead of print.

ABSTRACT

Aim: To investigate the efficacy of diode laser (DL), photodynamic therapy (PDT), and ozone water on the removal of smear layer (SL) and its assessment via scanning electron microscope (SEM) following its effect on shear bond strength (SBS) on carious affected dentin. Materials and Methods: Sixty-six caries-affected dentin (CAD) samples were obtained from the dental outpatient department. The occlusal enamel and infected dentin of the included samples were meticulously excised using a water-cooled, slow-speed device, resulting in a flat mid-coronal CAD surface. Based on the effectiveness of SL removal techniques, the samples were categorized into groups (n = 11 each). Group 1: no treatment, Group 2: DL, Group 3: PDT-activated methylene blue (MB), Group 4: 16 ppm ozonated water, Group 5: 17% ethylenediamine tetra-acetic acid (EDTA), and Group 6: 37% phosphoric acid (PA). One pair of samples from each group was assessed under SEM following different conditioning regimes. The remaining samples underwent the application of an adhesive 7th-generation single-bottle adhesive and composite placement. All bonded samples were aged, and SBS assessment was performed via a universal testing machine, and unbonded surfaces were assessed under a stereomicroscope. A one-way analysis of variance was employed, followed by Tukey honestly significant difference (HSD) post hoc tests. Statistical significance was established at a p value of less than 0.05. Results: The highest SL removal efficiency was observed in the PA group. The lowest SL removal efficacy was examined in the no-treatment group. SL removal efficiency via DL and EDTA was found to be comparable (p > 0.05) and significantly lower than samples conditioned with PA (p < 0.05). Samples conditioned with PDT-activated MB and ozonated water had comparable micro (μ)- SBS scores (p > 0.05). Samples conditioned via EDTA, PA, and diode demonstrated cohesive failure predominantly. Conclusions: PA is considered the benchmark for effectively removing the SL from dentin affected by caries, as it also enhances bonding strength. Nonetheless, EDTA and DLs present viable alternatives to phosphoric acid.

PMID:40762061 | DOI:10.1177/15578550251364114

Diabetes Obes Metab. 2025 Aug 5. doi: 10.1111/dom.70006. Online ahead of print.

ABSTRACT

AIMS: To assess the glycaemic efficacy and safety of CT-868, a cAMP signal-biased, dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, in participants with type 2 diabetes (T2D).

MATERIALS AND METHODS: This 26-week (W), phase 2, randomized, double-blind placebo-controlled trial enrolled adults with T2D, Body Mass Index ≥27 kg/m², and glycated haemoglobin (HbA1c) 7.0-10.0%. Participants were randomized (1:2:1) to once-daily CT-868 1.75 mg, 4.0 mg, or placebo. Due to COVID-19-related CT-868 supply constraints, some participants randomized to 4.0 mg received 3.25 mg maximum and were analysed as a separate dose arm. The primary endpoint was change from baseline in HbA1c at W26. Secondary endpoints included changes from baseline to W26 in fasting glucose, 7-point self-monitored blood glucose (SMBG), body weight, lipids and the occurrence of adverse events (AEs).

RESULTS: Overall, 103 participants were enrolled (CT-868 1.75 mg, n = 26; 3.25 mg, n = 18; 4.0 mg, n = 32; placebo, n = 27). Clinically meaningful and statistically significant improvements in HbA1c were observed with CT-868 at W26 (-1.61 to -2.24%-points vs. placebo; all p < 0.001). Body weight was modestly reduced with CT-868 4.0 mg at W26 (-2.9% vs. placebo, p < 0.001). CT-868 improved fasting glucose, SMBG, and most lipid parameters vs. placebo. AEs were mostly mild/moderate. No participants experienced hypoglycaemia.

CONCLUSIONS: CT-868 1.75 to 4.0 mg yielded robust, clinically meaningful decreases in HbA1c, supporting potent glycaemic-lowering effects and improved key lipid parameters in participants with overweight/obesity and T2D, despite modest weight loss. CT-868 was well tolerated, supporting future investigation of higher doses to maximize weight loss.

PMID:40762050 | DOI:10.1111/dom.70006

APMIS. 2025 Aug;133(8):e70055. doi: 10.1111/apm.70055.

ABSTRACT

This study is intended to expound the effect of clarithromycin combined with oxymetazoline hydrochloride (OZH) spray in acute exacerbations of chronic rhinosinusitis (AECRS). Patients with AECRS were retrospectively collected and divided into a control group and an observation group. The control group received clarithromycin, and the observation group received OZH spray in addition to clarithromycin. Symptom resolution time, nasal mucociliary transmission velocity, nasal endoscopy score, olfactory function, serum inflammatory factor levels, incidence of adverse reactions, and 6-month recurrence were recorded. After treatment, the observation group showed shorter resolution times for headache, runny nose, nasal congestion, and nasal mucosal edema; higher nasal mucociliary transport rate (MTR) and clearance (MCC); lower Lund-Kennedy score; more Grades I cases; fewer Grades III cases; lower levels of serum IL-6, TNF-α, hs-CRP, IL-8, and IL-1β; and lower recurrence rate than the control group (p < 0.05). The incidence of adverse reactions in the two groups was not statistically significant (p > 0.05). Clarithromycin combined with OZH spray is more effective in patients with AECRS, which can shorten symptom resolution time, increase nasal MTR, improve olfactory function, reduce inflammation and recurrence rates, and have a high degree of safety.

PMID:40762040 | DOI:10.1111/apm.70055