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Frontiers in Endocrinology 2024To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine...
Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors.
OBJECTIVES
To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs).
METHODS
A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed.
RESULTS
A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts.
CONCLUSION
A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.
Topics: Humans; Machine Learning; Pancreatic Neoplasms; Endosonography; Female; Male; Middle Aged; Insulinoma; Adult; Neuroendocrine Tumors; Diagnosis, Differential; Aged; Nomograms; Radiomics
PubMed: 38952387
DOI: 10.3389/fendo.2024.1383814 -
Annals of Geriatric Medicine and... Jul 2024Hip fractures are frequent injuries in older patients and are associated with high mortality rates. This study assessed the association between serum lactate level and...
BACKGROUND
Hip fractures are frequent injuries in older patients and are associated with high mortality rates. This study assessed the association between serum lactate level and 30-day mortality in older patients with unilateral hip fractures and examined the prognostic value of this association on the clinical outcomes of these patients.
METHODS
This retrospective, single-center study included patients aged ≥65 years admitted to the emergency department due to low-energy trauma and diagnosed with unilateral hip fracture upon admission. The additional inclusion criteria were patients with independent ambulation or walker or cane assistance before the injury, with available data on serum lactate levels on venous blood gas analysis, and who underwent surgery.
RESULTS
Among the 330 included patients, 30.9% experienced postoperative complications and 10.3% died within 30 days. Using a lactate cut-off value of 2 mmol/L to distinguish between living and deceased patients, the sensitivity and specificity were 41% and 88%, respectively. Multivariate logistic regression analysis revealed that high lactate and low albumin levels and male sex were associated with mortality.
CONCLUSION
Identifying risk factors for mortality in geriatric patients with hip fractures is important. Male sex, low albumin levels, and particularly increased lactate levels were independent predictors of short-term mortality in these patients.
PubMed: 38952335
DOI: 10.4235/agmr.24.0011 -
Turkish Journal of Orthodontics Jun 2024Expeditious strides in the fields of biomaterials, computer-aided design, and manufacturing have catapulted clear aligner therapy (CAT) to become a comprehensive...
Expeditious strides in the fields of biomaterials, computer-aided design, and manufacturing have catapulted clear aligner therapy (CAT) to become a comprehensive orthodontic treatment modality. The efficiency of achieving planned tooth movement with clear aligners is a significant consideration while setting up the final treatment goals, as well as calculating treatment times and costs based on the available evidence. Contemporary research outcomes confirm that one of the most commonly reported clinical concerns with CAT is the discrepancy between the prescribed outcome in the digital treatment plan and the clinically achieved outcome from a given series of aligners. Inaccurate prediction of tooth movements may not only lead to a prolonged duration of aligner treatment with an additional need for refinement strategies; but it may also cause other concerns, such as patient burnout and increased potential for relapse. The authors of this paper have elucidated some of the critical elements that may help address this discrepancy between digitally prescribed and clinical outcomes based on an evidence-based approach with regard to the predictability and accuracy of CAT. A strong diagnostic acumen, judicious case selection, solid biomechanical understanding of various types of orthodontic tooth movements, a research framework that keeps pace with technological and material developments and provides evidence-based knowledge of the limitations of CAT; and above all, the ability of the clinician to continually innovate as per different clinical scenarios, all contribute to attaining treatment predictability, efficacy, and efficiency with CAT.
PubMed: 38952301
DOI: 10.4274/TurkJOrthod.2024.2024.4 -
Journal of Obstetrics and Gynaecology :... Dec 2024The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth.
METHODS
On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software.
RESULTS
A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01).
CONCLUSIONS
The inflammatory biomarkers IL-1β, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.
Topics: Female; Humans; Pregnancy; Amniotic Fluid; Biomarkers; Inflammation; Interleukin-10; Interleukin-6; Matrix Metalloproteinase 9; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Premature Birth
PubMed: 38952221
DOI: 10.1080/01443615.2024.2368764 -
Epilepsia Open Jul 2024The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary...
The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. PLAIN LANGUAGE SUMMARY: This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity.
PubMed: 38952082
DOI: 10.1002/epi4.12968 -
Trials Jun 2024Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects,... (Comparative Study)
Comparative Study
Clinical trial results in context: comparison of baseline characteristics and outcomes of 38,510 RECOVERY trial participants versus a reference population of 346,271 people hospitalised with COVID-19 in England.
BACKGROUND
Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent.
METHODS
We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality.
RESULTS
Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3-24.1%]; vs reference 24.8% [24.6-25.0%]), except during the first pandemic wave in the UK (March-May 2020) when adjusted mortality was lower in RECOVERY.
CONCLUSIONS
Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates.
TRIAL REGISTRATION
ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020.
Topics: Humans; COVID-19; Male; England; Female; Middle Aged; Aged; Hospitalization; Aged, 80 and over; SARS-CoV-2; Comorbidity; Adult; Randomized Controlled Trials as Topic; Frailty
PubMed: 38951929
DOI: 10.1186/s13063-024-08273-9 -
Cardiovascular Diabetology Jul 2024The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine... (Meta-Analysis)
Meta-Analysis Review
The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI - 1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI - 1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.
Topics: Humans; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Adolescent; Child; Network Meta-Analysis; Female; Male; Treatment Outcome; Blood Glucose; Randomized Controlled Trials as Topic; Biomarkers; Bayes Theorem; Hypoglycemic Agents; Glycemic Control; Age Factors; Insulin; Dietary Supplements; Exercise Therapy; Exercise; Child, Preschool
PubMed: 38951907
DOI: 10.1186/s12933-024-02301-3 -
Journal of Translational Medicine Jul 2024Triple-negative breast cancer (TNBC) is a recurrent, heterogeneous, and invasive form of breast cancer. The treatment of TNBC patients with paclitaxel and fluorouracil...
BACKGROUND
Triple-negative breast cancer (TNBC) is a recurrent, heterogeneous, and invasive form of breast cancer. The treatment of TNBC patients with paclitaxel and fluorouracil in a sequential manner has shown promising outcomes. However, it is challenging to deliver these chemotherapeutic agents sequentially to TNBC tumors. We aim to explore a precision therapy strategy for TNBC through the sequential delivery of paclitaxel and fluorouracil.
METHODS
We developed a dual chemo-loaded aptamer with redox-sensitive caged paclitaxel for rapid release and non-cleavable caged fluorouracil for slow release. The binding affinity to the target protein was validated using Enzyme-linked oligonucleotide assays and Surface plasmon resonance assays. The targeting and internalization abilities into tumors were confirmed using Flow cytometry assays and Confocal microscopy assays. The inhibitory effects on TNBC progression were evaluated by pharmacological studies in vitro and in vivo.
RESULTS
Various redox-responsive aptamer-paclitaxel conjugates were synthesized. Among them, AS1411-paclitaxel conjugate with a thioether linker (ASP) exhibited high anti-proliferation ability against TNBC cells, and its targeting ability was further improved through fluorouracil modification. The fluorouracil modified AS1411-paclitaxel conjugate with a thioether linker (FASP) exhibited effective targeting of TNBC cells and significantly improved the inhibitory effects on TNBC progression in vitro and in vivo.
CONCLUSIONS
This study successfully developed fluorouracil-modified AS1411-paclitaxel conjugates with a thioether linker for targeted combination chemotherapy in TNBC. These conjugates demonstrated efficient recognition of TNBC cells, enabling targeted delivery and controlled release of paclitaxel and fluorouracil. This approach resulted in synergistic antitumor effects and reduced toxicity in vivo. However, challenges related to stability, immunogenicity, and scalability need to be further investigated for future translational applications.
Topics: Triple Negative Breast Neoplasms; Aptamers, Nucleotide; Humans; Paclitaxel; Nucleolin; Cell Line, Tumor; Animals; Female; Fluorouracil; Drug Liberation; RNA-Binding Proteins; Delayed-Action Preparations; Phosphoproteins; Oligodeoxyribonucleotides; Antineoplastic Combined Chemotherapy Protocols; Mice, Nude; Xenograft Model Antitumor Assays; Cell Proliferation; Oxidation-Reduction; Mice, Inbred BALB C
PubMed: 38951906
DOI: 10.1186/s12967-024-05429-8 -
BMC Complementary Medicine and Therapies Jun 2024Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC).
METHODS
We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance).
DISCUSSION
Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans.
TRIAL REGISTRATION
This protocol is registered at clinicaltrials.gov under study number NCT06213233.
Topics: Humans; Cannabidiol; Chronic Pain; Veterans; Double-Blind Method; United States; Analgesics; Male; Pragmatic Clinical Trials as Topic; Female; Adult; Middle Aged
PubMed: 38951902
DOI: 10.1186/s12906-024-04558-3 -
Journal of Cardiothoracic Surgery Jun 2024The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive...
BACKGROUND
The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive endovascular experience, focusing on exploring the outcome in long term follow-up.
METHODS
From 2006 to 2018, we conducted TEVAR on 97 patients presenting with various aortic pathologies. This retrospective cohort study was designed primarily to assess graft durability and secondarily to evaluate mortality causes, complications, reinterventions, and the impact of comorbidities on survival using Kaplan-Meier and Cox regression analyses.
RESULTS
The most common indication was thoracic aortic aneurysm (n = 52). Ten patients had aortic arch variations and anomalies, and the bovine arch was observed in eight patients. Endoleaks were the main complications encountered, and 10 of 15 endoleaks were type I endoleaks. There were 18 reinterventions; the most of which was TEVAR (n = 5). The overall mortality was 20 patients, with TEVAR-related causes accounting for 12 of these deaths, including intracranial bleeding in three patients. Multivariant Cox regression revealed chronic renal diseases (OR = 11.73; 95% CI: 2.04-67.2; p = 0.006), previous cardiac operation (OR = 14.26; 95% CI: 1.59-127.36; p = 0.01), and chronic obstructive pulmonary diseases (OR = 7.82; 95% CI: 1.43-42.78; p = 0.001) to be independent risk factors for 10-year survival. There was no significant difference in the survival curves of the various aortic pathologies. In the follow-up period, two non-symptomatic intragraft thromboses and one graft infection were found.
CONCLUSION
Comorbidities can increase the risk of TEVAR-related mortality without significantly impacting endoleak rates. TEVAR is effective for severe aortic pathologies, though long-term graft durability may be compromised by its thrombosis and infection.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Endovascular Procedures; Aorta, Thoracic; Aged; Blood Vessel Prosthesis Implantation; Treatment Outcome; Aortic Diseases; Postoperative Complications; Adult; Aortic Aneurysm, Thoracic; Follow-Up Studies; Time Factors; Endovascular Aneurysm Repair
PubMed: 38951901
DOI: 10.1186/s13019-024-02886-6