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Predictors for the pharmacological effect of ADHD medication in children and adolescents are lacking. This study examined clinically relevant factors in a large (N = 638) prospective cohort reflecting real-world evidence. Children and adolescents aged 6-17 diagnosed with ADHD were evaluated at baseline and three months following ADHD medication initiation. The outcome was measured as a reduction in total SNAP-IV (Swanson Nolan and Pelham teacher and parent rating scale) score at three months compared to baseline. Outcome groups were defined as Responders (≥ 40% reduction), Intermediate Responders (≥ 20 to < 40% reduction), and Non-responders (< 20% reduction). Included independent variables were the Autism Spectrum Questionnaire (ASSQ), the Spence Children's Anxiety Scale (SCAS), the Pediatric Side Effect Checklist (P-SEC), anthropometrics measures, geographical region, relative age, Children´s Global Assessment Scale (CGAS), Intelligence quotient (IQ), pharmacological treatment initiation month, ADHD symptom severity, ADHD presentation, and psychotic-like experiences. Multinomial logistic regression suggested that ADHD symptom severity, region, relative age, and stating ADHD medication at three-month follow-up were associated with the response outcome group. However, when validating the data with Bootstrap Forest, none of the variables were significant. Thus, in our large naturalistic cohort, we could not identify any clinically relevant factors that reliably predict pharmacological treatment outcomes.Trial registration: NCT02136147., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Aims: Admission hyperglycaemia is an adverse prognostic indicator in the setting of acute myocardial infarction. It is unclear if this is because of previously undiagnosed diabetes, due to admission plasma glucose being a marker of a greater stress hormone response and therefore a more severe event, or due to a detrimental effect of high blood glucose on the myocardium., Methods: We performed retrospective analysis of a cohort of 430 participants admitted with a diagnosis of acute myocardial infarction. We investigated the relation of admission plasma glucose, glycated haemoglobin, stress hyperglycaemia ratio and a novel parameter; the stress hyperglycaemia index, to mortality by Cox regression analyses. The stress hyperglycaemia index is the difference between the admission glucose and glucose estimated from HbA 1c ., Results: We included 430 participants who were followed for a median of 2.5 years. The stress hyperglycaemia index was associated with increased mortality in patients with diabetes in both univariate and multivariate analyses. Admission glucose was associated with mortality in subjects with diabetes in univariate analysis and after adjustment of age and sex, but not after adjusting for eGFR. There was no significant association between admission glucose and mortality in subjects without diabetes. HbA 1c was not associated with mortality in either patient group in both univariate and multivariate analyses., Conclusion: Our results suggest a possible detrimental effect of hyperglycaemia in the setting of an acute myocardial infarction., (© 2025 Diabetes UK.)

Objectives: Stress-induced hyperglycaemia (SIH) is an elevated blood glucose level (≥11.1 mmol/L) in patients experiencing physiological stress, in the absence of diabetes mellitus. Although early in-hospital SIH has been associated with worse outcomes following major trauma, the predictive value of SIH in the prehospital setting has not been established. To investigate the role of prehospital SIH as a predictor of in-hospital mortality following major trauma., Methods: A retrospective cohort study of non-diabetic, adult major trauma patients was undertaken to determine the association between prehospital SIH and in-hospital mortality. Secondary outcomes included ED disposition and ED length of stay., Results: Of 1179 trauma patients included, 89 (8%) had SIH. Prehospital SIH was associated with higher Injury Severity Scores (median (interquartile range): 25 (17-33) vs 17 (14-25)), lower GCS (GCS 3-7: 48.3% vs 10.9%, P < 0.001), lower systolic BP (mean (SD): 122 (44.0) vs 133 (30.3)), lower oxygen saturations (mean (SD): 88% (16) vs 96% (7)) and abnormal heart and respiratory rate. The in-hospital mortality rate was 9.9% in non-SIH patients and 42.7% among patients with SIH (odds ratio (OR): 6.8; 95% confidence interval (CI): 4.3-10.8, P < 0.001). The area under the receiver operating curve for blood glucose alone in predicting mortality was 0.65 (95% CI: 0.60-0.70). Prehospital blood glucose was an independent predictor of mortality after adjustment for age, sex, GCS and vital signs (adjusted OR = 2.9; 95% CI: 1.5-5.5, P = 0.001)., Conclusion: The present study demonstrated an association between prehospital SIH and in-hospital mortality following major trauma. Further prospective research is warranted to examine the utility and integration of prehospital SIH into predicting models of trauma care., (© 2024 Australasian College for Emergency Medicine.)

We investigated the context-dependent memory effect outside of the laboratory in order to examine whether the effect impacts everyday memory retrieval. We also examined various factors that may interact with the context-dependent memory effect such as frequency and context dwell time. In the experiment, we used a smartphone app to track participant's GPS locations for 5 weeks. Participants, during their daily lives, were then asked to recall their locations at a specific date and time by choosing from all locations visited in the previous 5 weeks. Results demonstrated the existence of the context-dependent memory effect in a real-world setting, with low-frequency locations showing a stronger context-dependent memory effect—benefiting more from the matched context. We also found that for low-frequency locations, the benefit of the context-dependent memory effect increased as the participant spent more time in the context (context dwelling time). The study provides a novel way to examine the context-dependent memory effect outside of the laboratory, which not only enables researchers to measure an individual's genuine memories in a more ecologically valid way, but also investigates factors that would be challenging to examine in the laboratory. [ABSTRACT FROM AUTHOR]

Background: The high costs associated with diabetes management, coupled with the increasing prevalence of comorbidities, present a significant challenge to China's healthcare system, with cardiovascular complications being particularly prominent. The purpose of this study was to evaluate the comorbidities of diabetic patients with stroke in Beijing from 2016 to 2018 and the impact on treatment options and associated costs. Methods: This retrospective cohort study included diabetic patients enrolled in Beijing's medical insurance with outpatient medical records. We compared comorbidities, medications, and related treatment costs between stroke and non-stroke patients. Results: A representative sample of 2,853,036 patients with diabetes was identified from the data collected from 2016 to 2018, of which an average of 21.18% of patients reported stroke. A higher percentage of diabetic patients with stroke reported other comorbidities including hypertension, coronary artery disease, dyslipidemia, chronic respiratory disease, and osteoporosis as compared to those without stroke(all p's < 0.0001). The costs increased dramatically if diabetic patients developed comorbidities, including hypertension, CAD, dyslipidemia, CRD, and osteoporosis. Annual costs of medications were higher for diabetic patients with stroke and any types of comorbidity compared to diabetic patients without stroke (p <.0001, respectively). More types of drugs were used for diabetic patients with stroke and any types of comorbidity. Conclusions: The needs of individuals with diabetes and stroke, including their comorbidity patterns and medical burdens, must be carefully taken into account. Health systems will need to address the increasing demand for diagnosing and managing comorbidities in individuals with diabetes and stroke. [ABSTRACT FROM AUTHOR]

Backgrounds: This study aimed to assess the association between fasting plasma glucose to glycated hemoglobin (FPG/HbA1c) ratio and mortality and to explore the mediating role of immunity and inflammation in diabetic and prediabetic populations. Methods: Our analysis included 10,267 participants with prediabetes or diabetes from the NHANES (1999-2018). The association between the FPG/HbA1c ratio and all-cause and cardiovascular(CVD) mortality was assessed using multivariate Cox proportional hazards models, restricted cubic splines(RCS), two-piecewise Cox proportional hazards models and sensitivity analysis. Mediation analysis was conducted to evaluate the systemic immune-inflammation index (SII) as a potential mediator. Results: Over a median follow-up of 103 months, there were 535 CVD deaths and 1918 all-cause deaths. After multivariate adjustment, a U-shaped relationship was observed between the FPG/HbA1c ratio and both CVD and all-cause mortality, with threshold points at 1.080 and 1.013, respectively. Below the thresholds, the FPG/HbA1c ratio was negatively associated with CVD mortality (HR:0.200, 95% CI: 0.072, 0.559) and all-cause mortality(HR: 0.242, 95% CI: 0.118, 0.494). Above the thresholds, the ratio was positively associated with CVD mortality (HR=3.691, 95% CI: 2.011, 6.772) and all-cause mortality (HR=3.025, 95% CI: 2.279, 4.016). Mediation analysis revealed that SII mediated 19.02% of the association with CVD mortality and 8.86% with all-cause mortality (P < 0.05). Conclusions: In the prospective cohort, the FPG/HbA1c ratio demonstrated a U-shaped association with mortality in diabetic and prediabetic adults, with SII playing a significant mediating role. These findings suggest that interventions targeting immunity and inflammation may improve clinical outcomes in these populations. [ABSTRACT FROM AUTHOR]

Background: While the cardiovascular risk of hyperglycemia has been thoroughly elucidated in patients with type 2 diabetes (T2DM) hospitalized for myocardial infarction, the evidence surrounding acute severe hyperglycemia is less well-established. Our study aimed to explore the impact of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), both severe hyperglycemic conditions, on cardiovascular outcomes in patients with T2D admitted for ST-elevation myocardial infarction (STEMI). Methods: We used the National Readmission Database (2016–2019) to extract patients with T2DM and STEMI at baseline. Subsequently, we selected cases of DKA and HHS. The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital acute renal failure, cardiogenic shock, and 30-day readmission and mortality. Results: The presence of DKA increased the adjusted odds of mortality and cardiogenic shock by almost 2-fold (adjusted Odds Ratios aOR = 2.30 [1.70–3.12], 2.055 [1.602–2.637], respectively) and renal failure by nearly 5-fold (aOR = 5.175 [4.090–6.546]). HHS was also associated with higher odds of mortality, acute renal failure, and cardiogenic shock. In 30 days, DKA and HHS increased the risk of readmission (aOR = 1.815 [1.449–2.75], 1.751 [1.376–2.228], respectively). There were no differences in the rates of cardiovascular disease, mortality, or other cardiovascular events between DKA and HHS patients. Within 30 days of readmission, DKA and HHS were associated with higher odds of readmission but not mortality. Cardiovascular disease was the most common etiology of readmission in all patients. The incidence of non-STEMI was the highest in DKA patients, and the incidence of STEMI was the highest in the HHS group. Conclusion: The presence of diabetic ketoacidosis or hyperglycemic hyperosmolar state is associated with higher odds of mortality, renal failure, cardiogenic shock, and 30-day readmission in STEMI patients with type 2 diabetes, highlighting the need for enhanced clinical management and monitoring of patients experiencing acute hyperglycemia. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) represents a major healthcare condition of the 21st century. It is characterised by persistently elevated blood glucose occurring as a result of peripheral insulin resistance and reduced insulin production which may lead to multiple long-term health conditions such as retinopathy, neuropathy, and nephropathy. The estimated number of individuals suffering from diabetes mellitus (DM) is expected to rise to 591 million by the year 2035 with 4.4 million in the United Kingdom (UK) alone, 90% of which is attributed to T2DM. Moreover, a significant proportion of individuals may have undetected diabetes mellitus, especially among those presenting with symptoms of ischaemic heart disease (IHD). This is particularly important in those individuals presenting with acute coronary syndromes (ACS) who are at the highest risk of complications and sudden cardiac death. Identifying abnormal levels of common biochemical markers of diabetes, such as capillary blood glucose or glycated haemoglobin (HbA1c) in these patients is important for early diagnosis, which will then allow for timely intervention to improve outcomes. However, a significant proportion of individuals who meet the criteria for the diagnosis of diabetes remain undiagnosed, representing missed opportunities for early intervention. This may result in a prolonged period of untreated hyperglycaemia, which can result resulting in significant further microvascular and macrovascular complications. There is an increased risk of IHD, heart failure, cerebrovascular accidents (CVA), and peripheral artery disease (PVD). These account accounting for 50% of deaths in patients with T2DM. Cardiovascular diseases in the context of diabetes particular represent a significant cause of morbidity and mortality with a two to three times higher risk of cardiovascular disease in individuals with T2DM than in those without the condition normo-glycaemia. In the United Kingdom UK alone, around 120 amputations, 770 CVA, 590 heart attacks, and more than 2300 presentations with heart failure per week are attributed to diabetes DM. with One 1 in six 6 hospital beds and around 10% of the healthcare budget may be being spent on managing diabetes DM or its complications. Therefore, it represents a significant burden on our healthcare system. [ABSTRACT FROM AUTHOR]

The effects of speech-based variables on the immediate serial recall (ISR) task constitute fundamental evidence underpinning the concept of the Phonological Loop component of Working Memory. Somewhat surprisingly, the Phonological Loop has yet to be applied to the immediate free recall (IFR) task although both tasks share similar memoranda and presentation methods. We believe that the separation of theories of ISR and IFR has contributed to the historical divergence between the Working Memory and Episodic Memory literature. We review more recent evidence showing that the two tasks are approached by participants in similar ways, with similar encoding and rehearsal strategies, and are similarly affected by manipulations of word length, phonological similarity, articulatory suppression/concurrent articulation, and irrelevant speech/sound. We present new analyses showing that the outputs of the two tasks share similar runs of successive items that include the first and last items– which we term start- and end-sequences, respectively—that the remaining residual items exhibit strong recency effects, and that start- and end-sequences impose constraints on output order that help account for error transposition gradients in ISR. Such analyses suggest that similar mechanisms might convey serial order information in the two tasks. We believe that recency effects are often under-appreciated in theories of ISR, and IFR mechanisms could generate error transpositions. We hope that our review and new analyses encourage greater theoretical integration between ISR and IFR and between the Working Memory and Episodic Memory literature. [ABSTRACT FROM AUTHOR]

Introduction: Advances in pharmacotherapy for coronary thrombosis treatment and prevention have transformed the clinical outcomes of patients with coronary artery disease but increased the complexity of therapeutic decision-making. Improvements in percutaneous coronary intervention techniques and stent design have reduced the incidence of thrombotic complications, which consequently has increased the challenge of adequately powering clinical trials of novel antithrombotic strategies for efficacy outcomes. Knowledge of the pathophysiology of coronary thrombosis and the characteristics of antithrombotic drugs can help with therapeutic decisions. Areas covered: This review covers the pathophysiology of coronary thrombosis and the mechanisms of action of drugs developed for its treatment, provides an overview of the key issues in decision-making, and highlights key areas for further work in order to guide clinicians on how to individualize risk management and address gaps in the evidence base. Expert opinion: Individualization of antithrombotic therapy regimens has become a vital part of optimizing risk management in people with coronary thrombosis. A critical appraisal of the strengths and limitations of available drugs and the evidence supporting the use of different antithrombotic combinations is intended to provide direction to clinicians and point the way toward further improvements in pharmacotherapy for coronary thrombosis treatment and prevention. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells. These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups. Toxicity profiles have generally shown favorable safety outcomes, with minimal incidence of severe adverse effects such as cytokine release syndrome (CRS) or graft-versus-host disease (GVHD). However, persistent challenges remain, including limited NK cell persistence, relapse, and heterogeneity in patient responses. This review provides a comprehensive analysis of clinical outcomes and toxicity profiles provided from clinical trials, clinical studies and case reports conducted in the last 15 years to judge on the efficacy, safety and applicability of using NK cells for ACT of AML. Our review highlights the significant potential of NK cell-based therapies for AML, while addressing the technical and biological challenges that must be overcome to enhance their efficacy and safety. [ABSTRACT FROM AUTHOR]

Delirium is an acute neuropsychiatric syndrome that recognizes one or more underlying causal medical conditions. Stress hyperglycemia usually refers to transient hyperglycemia associated with stress conditions such as stroke, myocardial infarction, and major surgery. Both delirium and stress hyperglycemia share common pathways, such as activation of inflammation. Stress hyperglycemia has been associated with negative outcomes, and recent studies suggested that there is an increased risk of delirium onset in patients with stress hyperglycemia. The purpose of this review is to illustrate the relationship between stress hyperglycemia and delirium. Initially, we illustrate the role of diabetes on delirium onset, summarize the criteria used for the diagnosis of stress hyperglycemia, discuss the impact of stress hyperglycemia on outcome, and focus on the evidence about the relationship between stress hyperglycemia and delirium. [ABSTRACT FROM AUTHOR]

Whey protein isolate (WPI) has functional properties such as gelation and emulsification. Emulsion gels combine the benefits of both emulsions and hydrogels. In this study, WPI hydrogels and emulsion gels were developed with goji oil (GO) as the oil phase by the inclusion of blueberry extract (BE) in the protein matrix. Heat-denatured WPI (hWPI) particles and emulsions were characterized in terms of size distribution, ζ-potential, interfacial protein, and anthocyanin partition. The inclusion of anthocyanins-rich blueberry extract led to the aggregation of hWPI particles, but it also increased the interfacial protein of 10% goji oil emulsions to 20% and decreased their size distribution to 120 and 325 nm. WPI hydrogels and emulsion gels were analyzed in terms of their water-holding capacity, which decreased from 98% to 82% with the addition of blueberry extract and goji oil. Syneresis, rheological, and morphological characteristics were also analyzed. The gelation time of hWPI particles and emulsions was shortened from 24 h to 12 h when incorporating blueberry extract to form a dense network. The network was the most homogeneous and densest in the presence of 3% blueberry extract and 5% goji oil. The co-inclusion of blueberry extract and goji oil increased the syneresis during the freeze–thaw cycles, with the values rising from 13% to 36% for 5% BE hydrogel and BE-containing emulsion gels after the first cycle. All WPI hydrogels and emulsion gels exhibit predominantly elastic behavior. Moreover, anthocyanin release, antioxidant activity, and the fatty acid composition profile were also analyzed during in vitro digestion. Soluble and free anthocyanins in the digested medium were reduced with the goji oil content but increased with the blueberry extract content. The stability of polyunsaturated fatty acids in the digested medium was improved by the addition of blueberry extract. The antioxidant activity of the digested medium increased with the content of blueberry extract but decreased with the content of goji oil. The ABTS∙+ scavenging capacities decreased from 63% to 49% by increasing the content of GO from 0% to 10% and they increased from 48% to 57% for 5% BE and 10% GO emulsion gels as the BE content increased from 0% to 5% after 6 h of digestion. The data gathered should provide valuable insights for future efforts to co-encapsulate hydrophilic and hydrophobic agents, thereby enhancing their stability, bioavailability, and functional properties for potential applications in food industries. [ABSTRACT FROM AUTHOR]

The activation of the bradykinin type 2 receptor is intricately involved in acute post-ischemic inflammatory responses. However, its precise role in different stages of ischemic injury, especially in the chronic phase, remains unclear. Following simultaneous cerebral and retinal ischemia, bradykinin type 2 receptor knockout mice and their controls were longitudinally monitored for 35 days via magnetic resonance imaging, fundus photography, fluorescein angiography, behavioral assessments, vascular permeability measurements, and immunohistochemistry, as well as glycemic status assessments. Without impacting the lesion size, bradykinin type 2 receptor deficiency reduced acute cerebral vascular permeability preventing the loss of pericytes and tight junctions. In the chronic phase of ischemia, however, it resulted in increased astrogliosis and cortical neuronal loss, as well as higher functional deficits. The retinal findings demonstrated a similar pattern. Bradykinin type 2 receptor deficiency delayed, but exacerbated the development of retinal necrosis, increased subacute vascular permeability, and promoted retinal ganglion cell loss in the chronic phase of ischemia. This investigation sheds light on the temporal dynamic of bradykinin type 2 receptor effects in ischemia, pointing to a therapeutic potential in the subacute and chronic phases of ischemic injury. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette–Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. Methods: We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls. The proliferation and production of cytokines and cytotoxicity were evaluated in peripheral blood mononuclear cells, stimulated in vitro with anti-CD3/CD28 or BCG, from selected patients based on HLA-B −21M/T dimorphism (NKG2A ligands). Results: The HLA-B −21M/T genotype showed opposing results in BC patients treated with BCG or other therapies. The MM genotype, compared to MT and TT, was associated with a longer 75th-percentile overall survival (not reached vs. 68.0 ± 13.7 and 52.0 ± 8.3 months, p = 0.034) in BCG, but a shorter (8.0 ± 2.4 vs. 21.0 ± 3.4 and 19.0 ± 4.9 months, p = 0.131) survival in other treatments. The HLA-B −21M/T genotype was an independent predictive parameter of the progression-free survival (HR = 2.08, p = 0.01) and the OS (HR = 2.059, p = 0.039) of BC patients treated with BCG, together with age and tumor histopathologic characteristics. The MM genotype was associated with higher counts of circulating CD56bright, fewer KIR2DL1/L2+ NK cells, and lower NKG2A expression, but not with differential in vitro NK cell functionality. Conclusions: The HLA-B −21M/T is independently associated with BC patient outcomes and can help to optimize the use of new immunotherapies in these patients. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the differences in plaque composition and burden between normal glycemic status (NGS) and dysglycemia expressed as impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). Methods: Clinically indicated coronary computed tomography angiography was used to evaluate patients with suspected coronary artery disease (CAD). An oral glucose tolerance test was performed to assess glycemic status. Patients were stratified as NGS, IGT, and T2DM. Plaque volumes were quantified using validated software, with further compositional measurements of low-attenuation, non-calcified, and calcified plaque burden. Results: Of 355 patients with suspected CAD, 220 had NGS, 92 were diagnosed with IGT, and 43 with known T2DM. Low-attenuation plaque volume was significantly higher in IGT (209 mm3, p < 0.02) and T2DM (243 mm3, p = 0.005) compared with NGS (166 mm3). Total plaque burden was similar between all groups, but a significantly greater low-attenuation plaque burden was seen in IGT (p = 0.03) and T2DM (p = 0.02) compared with NGS. The multivariate linear regression model adjusted for clinical risk factors showed that patients with IGT had a greater low-attenuation plaque burden compared with those with NGS (p = 0.03). Interestingly, no significant differences in plaque burdens were observed between those with IGT and T2DM in both univariate and multivariate analyses. Conclusions: Dysglycemia, including impaired glucose tolerance and type 2 diabetes mellitus, was associated with increased low-attenuation plaque burden compared with normal glycemic status. Patients with IGT demonstrated plaque burden similar to patients with known T2DM, underscoring the need for early metabolic intervention. [ABSTRACT FROM AUTHOR]

Atherosclerotic peripheral artery disease (PAD), that is, arteriosclerosis obliterans, is pathologically rooted in atherosclerosis, similar to other cardiovascular diseases. In addition to smoking, hypertension, and dyslipidemia, diabetes mellitus is a major risk factor. People with diabetes mellitus have an elevated risk of developing PAD. PAD in turn increases the risk of diabetic foot ulcers and gangrene in the population. Rest pain, nonhealing ulcers, and gangrene associated with chronic ischemia are known as chronic limb-threatening ischemia (CLTI). This article gives an overview of the link between atherosclerotic PAD, particularly CLTI, and diabetes mellitus. First, the clinical impact of CLTI among patients with diabetes mellitus is presented. Second, its clinical features, including prognosis, comorbidity, occurrence, and seasonality, are mentioned. The clinical management of CLTI is also discussed. Diabetes mellitus has notable clinical impact on CLTI and vice versa. CLTI has different clinical features from those of other atherosclerotic cardiovascular diseases. Its clinical profile also differs between individuals with both diabetes mellitus and CLTI and general people with diabetes mellitus. There is considerable room for improvement in CLTI treatment and management. Clinical measures taken before revascularization, including CLTI risk assessment, prompt diagnosis, and expedited referral to vascular specialists, may enhance CLTI outcomes. Further research is warranted to obtain more evidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Cell therapies have led to remarkable responses in patients with advanced hematologic cancers, but these results have not been as readily reproduced in solid tumor malignancies. Chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, T cell receptor-engineered (TCR-T) cells, and tumor-infiltrating lymphocytes (TILs) are adoptive cell therapies (ACTs) that are under investigation for treatment of multiple solid tumors, including the thoracic malignancies that will be the focus of this review. These therapies have enormous potential to help patients even with advanced and refractory disease, but much work remains to design safe and effective cell therapies for these diseases. Thoracic malignancies (lung cancers and malignant pleural mesothelioma) are prevalent worldwide and are associated with high morbidity and mortality. Effective treatments are needed for patients with advanced disease. Cell therapies are a promising approach to the treatment of advanced cancers that make use of immune effector cells that have the ability to mediate antitumor immune responses. In this review, we discuss the prospect of chimeric antigen receptor-T (CAR-T) cells, natural killer (NK) cells, T cell receptor-engineered (TCR-T) cells, and tumor-infiltrating lymphocytes (TILs) as treatments for thoracic malignancies. CAR-T cells and TILs have proven successful in several hematologic cancers and advanced melanoma, respectively, but outside of melanoma, results have thus far been unsuccessful in most other solid tumors. NK cells and TCR-T cells are additional cell therapy platforms with their own unique advantages and challenges. Obstacles that must be overcome to develop effective cell therapy for these malignancies include selecting an appropriate target antigen, combating immunosuppressive cells and signaling molecules present in the tumor microenvironment, persistence, and delivering a sufficient quantity of antitumor immune cells to the tumor. Induced pluripotent stem cells (iPSCs) offer great promise as a source for both NK and T cell-based therapies due to their unlimited expansion potential. Here, we review clinical trial data, as well as recent basic scientific advances that offer insight into how we may overcome these obstacles, and provide an overview of ongoing trials testing novel strategies to overcome these obstacles. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive primary brain tumor that carries a grim prognosis. Because of the dearth of treatment options available for treatment of GBM, Chimeric Antigen Receptor (CAR)-engineered T cell and Natural Killer (NK) therapy could provide alternative strategies to address the challenges in GBM treatment. In these approaches, CAR T and NK cells are engineered for cancer-specific immunotherapy by recognizing surface antigens independently of major histocompatibility complex (MHC) molecules. However, the efficacy of CAR T cells is hindered by GBM's downregulation of its targeted antigens. CAR NK cells face similar challenges, but, in contrast, they offer advantages as off-the-shelf allogeneic products, devoid of graft-versus-host disease (GVHD) risk as well as anti-cancer activity beyond CAR specificity, potentially reducing the risk of relapse or resistance. Despite CAR T cell therapies being extensively studied in clinical settings, the use of CAR-modified NK cells in GBM treatment remains largely in the preclinical stage. This review aims to discuss recent advancements in NK cell and CAR T cell therapies for GBM, including methods for introducing CARs into both NK cells and T cells, addressing manufacturing challenges, and providing evidence supporting the efficacy of these approaches from preclinical and early-phase clinical studies. The comprehensive evaluation of CAR-engineered NK cells and CAR T cells seeks to identify the optimal therapeutic approach for GBM, contributing to the development of effective immunotherapies for this devastating disease., Competing Interests: Declarations. Conflict of interest: All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent for publication: All authors give their consent to submission of this article to Journal of Neuro-oncology (JNO). Informed consent: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The antioxidant capacity of anthocyanins (AC) rapidly degrades during storage, highlighting the need for their stabilization. The conformational properties and high proline content of sodium caseinate (NaCAS), combined with the formation of NaCAS microgels in the presence of tara gum (TG) and acid gelation, suggest its potential as an effective stabilizing or encapsulating agent of AC., Results: Spectrofluorimetric results suggest the formation of a complex between NaCAS and AC. Fourier transform infrared spectroscopy demonstrated that the presence of TG and blackberry extract (BEX) modifies the NaCAS spectra in the analyzed range. These results validated the presence of hydrogen bonding and hydrophobic interactions between NaCAS and AC. The impact of the AC-NaCAS complex on the stability of the antioxidant capacity was assessed. After 43 days of storage, the lyophilized complex with an optimal BEX concentration retained 70% of its iron-reducing power. Additionally, the results indicate that, at the tested concentrations of BEX, the radical scavenging capacity of NaCAS is minimally affected., Conclusion: The present study demonstrates that the bioactive properties of the aqueous extract of blackberry are effectively stabilized through the formation of complexes with NaCAS in the presence of TG. Both AC and TG interact with NaCAS, but in different ways. The antioxidant capacity of these mixtures, demonstrated through both reducing power and free radical capture, is preserved to a high degree after storage. © 2025 Society of Chemical Industry., (© 2025 Society of Chemical Industry.)

Long-term data are limited comparing percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (S-DES) vs coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD). We aimed to conduct a systematic review and meta-analysis comparing these interventions in patients with left main or multivessel CAD. We systematically reviewed PubMed, Embase, and Cochrane for studies that compared PCI with S-DES and CABG in patients with left main or multivessel CAD with a minimum mean follow-up period of 3 years. Outcomes of interest were all-cause mortality, myocardial infarction (MI), stroke, and major adverse cardiovascular events (MACE). We extracted data from observational studies as multivariable-adjusted or propensity score-matched hazard ratio to minimize confounding and pooled hazard ratios with 95% confidence intervals (CIs) using a random effects model in Review Manager 5.4.1. We included 10 studies, 3 of which were randomized controlled trials, comprising a total of 26964 patients, of whom 14928 underwent PCI. As compared with CABG, S-DES had a significantly higher risk of all-cause mortality (hazard ratio 1.35; 95% CI 1.22-1.49; P < 0.001; I2 = 0%), MACE (hazard ratio 1.27; 95% CI 1.08-1.50; P = 0.005; I2 = 67%), and MI (hazard ratio 2.43; 95% CI 1.80-3.28; P < 0.01; I2 = 0%). There was no significant difference between groups in incidence of stroke. In this meta-analysis of patients with complex CAD, PCI with S-DES was associated with an increased risk of mortality, MI, and MACE compared with CABG., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dysglycaemia metrics, defined as hyperglycaemia, increased glucose variability, hypoglycaemia and reduced time in the targeted blood glucose range (TIR), are linked to higher mortality. The relationship between dysglycaemia metrics and intensive care unit (ICU) mortality over time for patients with and without diabetes remains inconclusive, posing challenges for ICU medical staff in accurately identifying and distinguishing various risk factors and taking timely and appropriate responses., Aim: To explore which dysglycaemia metrics within the first 7 days of ICU stay are associated with ICU mortality among patients with and without diabetes., Study Design: This retrospective cohort study included 712 patients without diabetes and 222 patients with diabetes. Clinical data were collected within the first 7 days of ICU stay. Binary logistic regression models were built to analyse which dysglycaemia metrics (hyperglycaemia, coefficient of variation [CV], hypoglycaemia and TIR) on the first day, over the first 3, 5 and 7 days of ICU stay were associated with ICU mortality., Results: In patients with diabetes, hyperglycaemia on the first day (OR: 4.90, 95% CI: 1.51-15.90, p = .008) and TIR <70% during the first 7 days of ICU stay (OR: 16.31, 95% CI: 1.50-176.89, p = .022) were associated with increased ICU mortality. In patients without diabetes, CV >20% on the first day (OR: 1.46, 95% CI: 1.03-2.07, p = .035), and TIR <70% during the first 3 (OR: 2.01, 95% CI: 1.35-2.98, p < .001) and 5 days (OR: 1.66, 95% CI: 1.09-2.54, p = .019) were associated with increased ICU mortality (p < .05). The proportion of hypoglycaemia did not significantly correlate with ICU mortality in patients with or without diabetes (p > .05)., Conclusions: Specific dysglycaemia metrics are associated with ICU mortality between patients with and without diabetes. In patients with diabetes, hyperglycaemia on the first day and TIR <70% on the first 7 days with higher mortality. In patients without diabetes, CV >20% on the first day and TIR <70% in the first 3 and 5 days are associated with higher mortality. Monitoring these metrics may potentially help develop strategies to decrease ICU mortality through individualized glycaemic management., Relevance to Clinical Practice: Close monitoring of dysglycaemia metrics, especially TIR, and personalized glucose management based on diabetic status may help identify high-risk ICU patients and improve targeted care strategies., (© 2025 British Association of Critical Care Nurses.)

In the acute stage of stroke, stress hyperglycemia is common in both diabetic and nondiabetic patients. The associations between stress hyperglycemia and functional outcomes, as well as stroke recurrence were heterogeneous in previous studies. We aimed to demonstrate these associations in a general population of patients with ischemic stroke and transient ischemic attack (TIA). We included patients with complete data on blood glucose and hemoglobin from The Third China National Stroke Registry. The stress hyperglycemia ratio (SHR) was calculated using fasting blood glucose (mmol/L) divided by glycosylated hemoglobin A1c (%). Outcomes included functional disability, recurrent ischemic stroke and TIA, combined vascular events, and all-cause mortality at 90 days. In total, 7186 patients were included (median age: 62 [54-70] years, male: 4864 [67.69%], TIA: 589 [8.20%]). SHR levels were significantly associated with functional disability (adjusted OR: 1.69, 95%CI: 1.22-2.33). For every 1 standard deviation increment in SHR, the risk of functional disability increased by 13%. Compared to the patients in SHR Tertile 1, those in Tertile 3 had a 1.31-fold increased risk of functional disability (95%CI: 1.08-1.60). There was a trend indicating that the risk of functional disability increased with higher SHR tertiles (P for trend = 0.0074). Stroke severity explained 42.94% of the total excess association between SHR and functional disability. However, neither SHR levels nor SHR tertiles were associated with recurrent ischemic stroke and TIA, combined vascular events, or all-cause mortality. This study found that admission stress hyperglycemia was associated with functional disability, which was partially mediated by stroke severity., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the Beijing Tiantan Hospital (IRB approval number: KY2015-001-01). All participants have provided their written informed consents. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Current treatments for retinal disorders are anti-angiogenic agents, laser photocoagulation, and photodynamic therapies. These conventional treatments focus on reducing abnormal blood vessel formation in the retina, which, in a low-oxygen environment, can lead to harmful proliferation of endothelial cells. This results in dysfunctional, leaky blood vessels that cause retinal edema, hemorrhage, and vision loss. Age-related Macular Degeneration is a primary cause of vision loss and blindness in the elderly, impacting around 20% of those over 50 years old. This complex disease is also closely related to oxidative stress in retina. In this review, we explore the challenge of treating retinal diseases, alternatives and possibilities of enhancing the effectiveness of therapies using co-delivery systems containing both antiangiogenic and antioxidant therapeutic agents. Despite recent proposals potential, the lack of extensive clinical studies on the long-term outcomes and optimal combinations of therapies means that the full risk profile and effectiveness of combined therapy are not yet completely understood. These factors must be carefully considered and managed by healthcare providers to optimize treatment outcomes and ensure patient safety., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests. Consent to publish: All authors agree to publish this article in Drug Delivery and Translational Research., (© 2024. Controlled Release Society.)

The gold(I) N-heterocyclic carbene (NHC) molecule exhibits outstanding luminescent properties along with high thermal stability due to its strong carbene gold bond. Gold(I)-NHC complexes are known to emit green to yellow color, while blue emission is limited. Herewith, we report the photoluminescence and thermal stability correlation between blue emitting mononuclear gold(I)-NHC chloride complexes, N-(9-anthracenyl)-N'(n-alkyl)imidazol-2-ylidene gold(I) chloride (alkyl=n-butyl (1), n-pentyl (2), n-hexyl (3)). These complexes were synthesized by transmetallation route and characterized by FT-IR, NMR, TGA, and single crystal X-ray diffraction analysis. The solid-state study reveals a unique molecular packing due to hydrogen bonding, aurophilic interaction, and CH⋅⋅⋅π interactions in all 1-3. In addition, the π⋅⋅⋅π stacking has been found in 1. All these complexes show good thermal stability due to the strong metal-ligand bond strength along with crystal packing. In addition, 1-3 emits a blue colour in both solution and crystalline state. The quantum yield in the crystalline state was found to be higher for 1 (22.44 %) compared to 2 (9.90 %), and 3 (14.98 %). A similar high quantum yield for blue-emitting gold(I)-NHC chloride complex is rare. This promising quantum yield for 1 can be ascribed to the crystal packing effect. The theoretical calculations were carried out to understand the electronic and structural properties of 1-3. Computational studies revealed the origin of the luminescence behaviour of complexes. The blue light emitting thin film and LED are demonstrated using 1 exhibited the emission peak at the blue region with Commission Internationale de L'Eclairage (CIE) coordinates near the National Television Standards Committee (NTSC) value., (© 2025 Wiley-VCH GmbH.)

Chimeric antigen receptor (CAR) T cells are revolutionizing cancer therapy, particularly for haematological malignancies, conferring durable and sometimes curative responses in patients with advanced-stage disease. The CAR T cell products currently approved for clinical use are all autologous and are often effective; however, in patients who are lymphopenic and/or heavily pretreated with chemotherapy, autologous T cells can be difficult to harvest in sufficient numbers or have functional impairments that might ultimately render them less efficacious. Moreover, autologous products take several weeks to produce, and each product can be used in only one patient. By contrast, allogeneic CAR T cells can be produced for many patients using T cells from a single healthy donor, can be optimized for safety and efficacy, can be instantly available for 'off-the-shelf' use and, therefore, might also be more cost-effective. Despite these potential advantages, the development of allogeneic CAR T cells has lagged behind that of autologous products, owing to the additional challenges such as avoiding graft-versus-host disease and host-mediated graft rejection. Over the past few years, the development of advanced genome-editing techniques has facilitated the generation of novel allogeneic CAR T cell products. Furthermore, CAR cell products derived from other cell types such as induced pluripotent stem cells and natural killer cells are being investigated for clinical use. In this Review, we discuss the potential of allogeneic CAR cell products to expand life-saving immunotherapy to a much broader population of patients in the coming years, the progress made to date and strategies to overcome remaining hurdles., Competing Interests: Competing interests: D.T.T. serves on advisory boards (unpaid) for Amgen, BEAM Therapeutics, Janssen, Jazz Pharmaceuticals, Servier and Sobi; receives research funding from BEAM Therapeutics; and has patents pending relating to cytokine-release syndrome after chimeric antigen receptor (CAR) T cell therapy and to CD38-directed CAR T cells. S.A.G. receives research funding from Cellectis, Kite (a GILEAD company), Novartis, Servier and Vertex; consults for Adaptive Biotech, Eureka Therapeutics, Estrella Immunopharma, Jazz Pharmaceuticals and Novartis; and has advised for Allogene, Cabaletta Bio, Jazz Pharmaceuticals, Novartis, Verismo and Vertex, and has patents related to CAR T toxicity managed by the University of Pennsylvania. C.D. declares no competing interests., (© 2024. Springer Nature Limited.)