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Impact of specialised endocrinology care on metabolic control and healthcare utilisation outcomes after kidney transplantation in patients with diabetes: A 12-month observational cohort study.3 weeks agoTo evaluate whether an endocrinology-integrated transplant clinic and differing healthcare delivery models are associated with metabolic outcomes during the first year after kidney transplantation in recipients with pre-existing diabetes.
We conducted a retrospective longitudinal cohort study of adult kidney transplant recipients with diabetes at a US and a European academic centre. Participants were classified by post-transplant diabetes care model: Cohort 1, endocrinology-led Endocrine Transplant Clinic (ETC; n = 99); Cohort 2, historical standard transplant care at the same US centre (n = 81); and Cohort 3, standard endocrinology care at a Spanish academic centre (n = 40). Pre-specified outcomes included HbA1c, body mass index (BMI), blood pressure, and lipid levels measured at baseline and 3, 6, and 12 months. Linear mixed-effects models adjusted for demographic and clinical covariates were applied. Missing longitudinal data were addressed using multiple imputation with complete-case sensitivity analyses.
Among 220 recipients, adjusted metabolic trajectories were broadly similar across cohorts. HbA1c was unchanged at 3 and 6 months but higher at 12 months; >50% had HbA1c >7% at 1 year. BMI remained stable, with ≥30% meeting obesity criteria throughout follow-up. Blood pressure did not improve, and systolic hypertension (>130 mmHg) remained common (49%-77%). At 12 months, LDL-C ≥70 mg/dL was present in 20.8%, 63.3%, and 42.3% of Cohorts 1-3. Findings were consistent in sensitivity analyses.
Metabolic control in the first post-transplant year showed stabilisation rather than improvement, with many recipients above cardiometabolic targets. Prospective studies should test whether earlier, protocolised multidisciplinary management improves cardiovascular and graft outcomes.DiabetesCare/Management -
How to treat diabetes mellitus in the older patients: being risk averse versus being too progressive.3 weeks agoDiabetesCare/Management
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Up-Regulation of microRNA-185-5p Alleviates Placental Inflammatory Response in Gestational Diabetes Mellitus by Regulating CDC42.3 weeks agoGestational diabetes mellitus (GDM) is a common pregnancy-related disorder characterized by insulin resistance, chronic inflammation, and placental dysfunction. MicroRNAs (miRNAs) are important regulators of placental development and immune homeostasis. This study investigates the role of miR-185-5p in GDM-associated placental inflammation via the CDC42-JNK/P38 MAPK-ATF2 pathway. CDC42 was identified as a predicted miR-185-5p target using public databases. Placental tissues from GDM patients and controls were analyzed for miR-185-5p and CDC42 expression by RT-qPCR, and direct binding was verified by dual-luciferase assay. A high-glucose-induced HTR8/SVneo trophoblast model was used to test the effects of miR-185-5p and CDC42 modulation on proliferation, apoptosis, and cytokine release. In vivo, a GDM mouse model was used to evaluate placental inflammation, structure, and signaling changes after intervention. miR-185-5p was downregulated and CDC42 upregulated in GDM placentas, with a significant inverse correlation. miR-185-5p directly bound to the 3'-UTR of CDC42. In high-glucose-treated HTR8/SVneo cells, upregulation of miR-185-5p or silencing of CDC42 reversed glucose-induced proliferation inhibition, reduced apoptosis, and suppressed TNF-α, IL-6, and IL-1β levels. In GDM mice, miR-185-5p overexpression or CDC42 knockdown significantly reduced placental and serum pro-inflammatory cytokine expression, suppressed phosphorylation of JNK and P38 MAPK, and downregulated downstream ATF2. miR-185-5p targets CDC42 to regulate the JNK/P38 MAPK-ATF2 pathway, thereby attenuating placental inflammation in GDM. This axis may contribute to the chronic inflammatory mechanisms underlying GDM-related placental dysfunction.DiabetesPolicy
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Astragaloside IV prevents calpain-1-mediated cardiac hypertrophy and fibrosis induced by diabetes.3 weeks agoAstragaloside IV (AsIV) has been reported to alleviate diabetes-induced endothelial dysfunction by inhibiting calpain-1. This study aimed to determine whether the same mechanism underlies its protective effect against diabetic cardiomyopathy (DCM).
At the in vivo level, calpain-1 knockout mice with the genotype Capn1 EK684-/- (Capn1 EK684 knockout mice) were used to establish a type 2 diabetic cardiomyopathy model. At the in vitro level, H9c2 cells and cardiac fibroblasts were stimulated with high glucose to construct corresponding models. Meanwhile, a calpain-1 overexpression lentivirus was constructed to assess the effect of calpain-1 on myocardial cell injury. Different doses of AsIV were then used to intervene in diabetic mice and H9c2 cells. Body weight, blood glucose, myocardial hypertrophy, myocardial fibrosis, cardiac function, Ca2+ overload and its regulation, myocardial cell apoptosis and oxidative stress were evaluated in the current study.
AsIV could not completely normalize blood glucose in mice, but could significantly improve cardiac systolic and diastolic function, myocardial hypertrophy and fibrosis. The beneficial effect of calpain-1 gene knockout on diabetic cardiomyopathy was similar to that of AsIV, and calpain-1 knockout did not further enhance the beneficial effect of AsIV. Calpain-1 overexpression abolished the beneficial effect of AsIV on high glucose induced H9c2 cell injury and fibroblast proliferation. In addition, the intracellular Ca2+ overload, abnormal levels of sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a), phosphorylation of phospholamban (p-PLN) and ryanodine receptor 2 (p-RyR2), apoptosis and oxidative stress associated with DCM were also improved by AsIV or calpain-1 knockout, and AsIV has the capacity to suppress the overactivation of calpain-1 and calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII).
AsIV could ameliorate intracellular Ca2+ overload, apoptosis, and oxidative stress by regulating the calpain-1/CaMKII pathway, thereby improving myocardial hypertrophy and fibrosis caused by diabetes mellitus.DiabetesPolicy -
A 10-year retrospective study of the clinical presentation, pathology, treatment and outcomes of ameloblastoma and ameloblastic carcinoma in a teaching hospital in Lagos, Nigeria.3 weeks agoBackground Ameloblastoma is a common benign, odontogenic tumour with high prevalence in Africans, particularly Nigerians. We describe the epidemiology, clinicopathology, pattern of management and incidence of recurrence of ameloblastoma and ameloblastic carcinoma, in Lagos, Nigeria. Methods This retrospective study included ameloblastoma cases surgically managed at the Lagos University Teaching Hospital from January 2012 to December 2021. Primary outcome was recurrence; secondary outcomes were length of hospital (LOH) stay and postoperative complications. Results We included 63 patients with a mean (SD) age of 34.2 (14.8) years, peak incidence (31.7%) in the 3rd decade of life, and male-to-female ratio of 1.03. The most common location, radiological feature and histological type were posterior mandible (77.8%), multilocular radiolucency (90.5%) and follicular ameloblastoma (50.8%), respectively. For surgical intervention, majority of patients had nasotracheal intubation (67.3%) and mandibulectomy (88.9%), and the most common surgical approach was extraoral (67.3%). The mean (SD) LOH stay was 9.4 (2.4) days, and the transoral approach was associated with shortened LOH. The mean follow-up was 2.7 years, and recurrence was recorded in 2 patients who had conventional ameloblastoma, and one who had ameloblastic carcinoma at 3 years and 3 months postoperatively, respectively. No significant association was noted for recurrence-free survival based on tumour size, tumour diagnosis, histological type and surgical approach (p>0.05). Conclusion Although the epidemiology, clinicopathology and treatment of ameloblastoma reported were similar to older reports, this study provides more recent information on the persistent public health burden of ameloblastoma, which can be used for comparisons with ameloblastoma in other populations.CancerAccessCare/ManagementAdvocacy
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Stereotactic two-needle irreversible electroporation of liver tumors near critical structures: a proof-of-concept study.3 weeks agoIrreversible electroporation (IRE) is a non-thermal ablation technique suitable for tumors near critical structures, but its widespread use is limited by technical complexity and the need for multiple electrodes. This study aimed to evaluate the feasibility, safety, and efficacy of a stereotactic percutaneous two-needle IRE approach for small liver tumors in anatomically challenging locations.
In this retrospective study, 17 consecutive patients with 18 primary or secondary liver tumors (≤ 2.0 cm) adjacent to critical anatomical structures underwent CT-navigated stereotactic two-needle IRE between December 2021 and May 2025. Ablation was performed with a high-dose protocol (2 × 90 pulses, 90 µs, > 20 A). Primary endpoints were primary technique efficacy (PTE) and local tumor progression (LTP); secondary endpoints included complications. Needle placement was assessed through geometric analysis.
PTE was obtained in 17/18 tumors (94.4%, 95% confidence interval (CI): 72.7-99.9%). At a median follow-up of 12.4 months, LTP occurred in 1/18 tumors (5.6%, 95% CI: 0.1-27.3%). No complications or procedure-related mortality were observed. Geometric analysis showed high accuracy of stereotactic needle placement, while treatment failure was associated with suboptimal geometry.
Stereotactic percutaneous two-needle IRE seems to be technically feasible with a favorable safety profile for small liver tumors in anatomically challenging locations and may offer a simplified alternative to multielectrode approaches. However, given the small, retrospective single-center design, these findings are preliminary and require prospective multicenter validation to establish oncologic effectiveness and generalizability.
Stereotactic two-needle irreversible electroporation offered a simplified, safe, and effective alternative to multielectrode ablation, potentially broadening treatment options for liver tumors near critical structures and improving accessibility, reproducibility, and outcomes in interventional oncology.
First systematic clinical evaluation of stereotactic two-needle irreversible electroporation (IRE) for liver tumors. Two-needle configuration with high-dose protocol simplifies IRE compared with standard multielectrode approaches. This proof-of-concept study demonstrates high efficacy and absence of complications in small liver tumors near critical structures. Two-needle IRE may broaden clinical applicability in anatomically challenging locations.CancerAccessCare/ManagementAdvocacy -
Acquisition, image quality, and PI-RADS agreement of ultrahigh-gradient DWI in prostate 3-T MRI.3 weeks agoNew magnetic resonance imaging (MRI) gradient technology enables the acquisition of ultrahigh b-value diffusion-weighted imaging (DWI). We assessed its impact on image quality and Prostate Imaging Reporting and Data System (PI-RADS) scores in prostate MRI.
Participants with cancer suspicion prospectively underwent 3-T prostate MRI (maximum gradient strength 200 mT/m). Sequences with b-values of 0/800, 1,500, 2,500, 3,500, and 4,500 s/mm² were acquired. Lesion conspicuity was rated from 1 (non-diagnostic) to 5 (excellent). Apparent signal-to-noise ratios (aSNR) and acquisition times were determined. Cumulative link mixed-effects models, repeated measures ANOVA, and Cohen/Fleiss κ statistics were used.
A total of 107 participants, aged 67 ± 8 years (mean ± standard deviation), were included. Compared to DWI(b1500), the DWI(b2500), DWI(b3500), and DWI(b4500) acquisitions were worse regarding both lesion conspicuity (median score, 5 [interquartile interval 4-5] versus 4 [3-4] versus 2 [2-3] versus 2 [1-2], respectively; all p < 0.001) and aSNR (19.0 ± 7.5 versus 12.7 ± 4.8 versus 11.8 ± 4.1 versus 11.4 ± 2.6, respectively; all p < 0.001). Acquisition times increased from DWI(b1500) (107 ± 9 s) to DWI(b4500) (329 ± 26 s). Cohen κ for PI-RADS score agreement was good to moderate (DWI(b2500): 0.87 [confidence interval 0.81, 0.94]; DWI(b3500): 0.75 [0.65, 0.84]; DWI(4500): 0.61 [0.49, 0.72]).
Acquired ultrahigh gradient DWI sequences with ultrahigh b-values in prostate MRI had worse image quality than standard b-values, while PI-RADS agreement between DWI(b1500) and DWI(b2500) was good. However, diagnostic estimates for clinically significant prostate carcinoma remained limited due to a small biopsy sample size (50/107 patients).
Ultrahigh b-value DWI showed no improved diagnostic performance in comparison to standard b-value DWI regarding the identification of potential prostate cancer. Ultrahigh b-value should not replace standard high b-values (1,500 s/mm²) for imaging workup of patients with suspicion for prostate cancer.
Acquired ultrahigh b-values (b2500-4500) using ultrahigh gradients of up to 140 T/m were utilized for prostate DWI. Both, overall image quality and diagnostic confidence decreased from good for DWI(b1500) to non-diagnostic for DWI(b4500). PI-RADS agreement between DWI(b1500) and DWI(b2500) was good, while it was only moderate between DWI(b1500) and DWI(b4500).CancerAccessAdvocacy -
Prognostic significance of circulating tumor DNA in early breast cancer: a systematic review and meta-analysis.3 weeks agoCirculating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in early-stage breast cancer (EBC). Despite growing interest, the prognostic impact of ctDNA detection in this setting remains to be fully elucidated.
A systematic review and meta-analysis were conducted on prospective studies assessing the association between ctDNA positivity and outcomes in early or locally advanced non-metastatic breast cancer. Databases including PubMed and the Cochrane Library were systematically searched. Studies were included if they reported hazard ratios (HRs) for disease-free survival (DFS) and/or overall survival (OS) according to ctDNA status. Pooled HRs were calculated using random-effects models; heterogeneity was evaluated with the I2 statistic.
Eighteen studies comprising 1670 patients were included. ctDNA positivity was significantly associated with shorter DFS (pooled HR 6.92, 95% CI 3.64-13.13; p < 0.0001; I2 = 79.7%). This association held across subtypes and timepoints, including post-surgical and longitudinal assessments. In the neoadjuvant setting, ctDNA positivity was associated with increased recurrence risk (HR 6.06, 95% CI 2.85-12.87; p < 0.0001), while in the adjuvant setting, it was an even stronger predictor of relapse (HR 14.76, 95% CI 1.11-197.02; p = 0.042). In a combined early-stage setting, ctDNA positivity correlated with significantly worse DFS (HR 6.55, 95% CI 1.41-30.39; p = 0.017). A non-significant trend was observed for worse OS (HR 3.91, 95% CI 0.78-19.72; p = 0.098).
ctDNA positivity is a robust prognostic biomarker for recurrence in early breast cancer. Its integration into post-treatment surveillance and interventional trials may enable risk-adapted strategies and early therapeutic intervention.CancerAccess -
Soft tissue augmentation options for volume replacement following parotidectomy: A review of the literature.3 weeks agoSalivary gland tumors primarily arise in the parotid gland with surgery representing the cornerstone of treatment. Parotidectomies often lead to a soft tissue deficit that may benefit from reconstruction to reduce incidence of Frey's syndrome, improve aesthetic outcomes, and allow for appropriate postoperative therapies. Several options exist including avascular tissue transfer, locoregional tissue flaps, and microvascular free flaps.
This paper is a literature review exploring the efficacy of the various reconstructive options, and includes randomized control trials, prospective studies, and retrospective studies from 1999 to 2024.
The literature demonstrates that any reconstructive option is superior to no reconstruction in reducing the risk of FS and in improving cosmetic outcomes without increasing the risk of postoperative complications including hematomas and sialoceles.
While literature demonstrates that reconstruction is beneficial in parotidectomies, the existing literature does not provide an adequate comparison of options to guide surgeons in making an informed choice.CancerAccess -
Ovarian function suppression decision-making and uptake in premenopausal women with breast cancer: a mixed methods analysis.3 weeks agoOvarian function suppression (OFS) reduces the risk of recurrence of hormone receptor-positive breast cancer but increases the likelihood of toxicity and nonpersistence with endocrine therapy. In addition, rates of OFS utilization are lower than expected. To increase understanding of these issues, we sought to identify patient factors associated with the use of OFS injections, as well as treatment decision-making and education needs.
In this convergent mixed methods designed study, patients receiving OFS, who started then discontinued OFS injections, and who never initiated OFS injections underwent 1:1 semi-structured interviews and completed questionnaires on shared decision-making and medication beliefs.
Of 33 enrolled participants, 30 completed both the questionnaires and the interview. Median age was 43 (range 32-55), 24 were white (80%), and 20 (66.7%) had received chemotherapy. Four key themes emerged. (1) There was concern about need for more education, especially about short- and long-term side effects of OFS. (2) For those receiving OFS injections, the decision to take OFS was mainly due to a desire to reduce cancer recurrence risk. (3) For those who stopped OFS, injections were often used as a stop-gap measure, with a preference for permanence of oophorectomy. (4) For those who never took OFS, there was often perceived lack of strong physician recommendation.
Tailored support for patients is needed to optimize decision-making regarding OFS, related to both potential benefits and risks of OFS in addition to adjuvant endocrine therapy. Educational strategies such as peer mentors or decision aids should be explored in this clinical setting.CancerAccessCare/ManagementAdvocacy