Barriers to early diagnosis of chronic kidney disease and use of sodium-glucose cotransporter-2 inhibitors for renal protection: A comprehensive review and call to action.

Chronic kidney disease (CKD) affects approximately 13% of people globally, including 20%-48% with type 2 diabetes (T2D), resulting in significant morbidity, mortality, and healthcare costs. There is an urgent need to increase early screening and intervention for CKD. We are experts in diabetology and nephrology in Central Europe and Israel. Herein, we review evidence supporting the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for kidney protection and discuss barriers to early CKD diagnosis and treatment, including in our respective countries. SGLT2 inhibitors exert cardiorenal protective effects, demonstrated in the renal outcomes trials (EMPA-KIDNEY, DAPA-CKD, CREDENCE) of empagliflozin, dapagliflozin, and canagliflozin in patients with CKD. EMPA-KIDNEY demonstrated cardiorenal efficacy across the broadest renal range, regardless of T2D status. Renoprotective evidence also comes from large real-world studies. International guidelines recommend first-line SGLT2 inhibitors for patients with T2D and estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2, and that glucagon-like peptide-1 receptor agonists may also be administered if required for additional glucose control. Although these guidelines recommend at least annual eGFR and urine albumin-to-creatinine ratio screening for patients with T2D, observational studies suggest that only half are screened. Diagnosis is hampered by asymptomatic early CKD and under-recognition among patients with T2D and clinicians, including limited knowledge/use of guidelines and resources. Based on our experience and on the literature, we recommend robust screening programmes, potentially with albuminuria self-testing, and SGLT2 inhibitor reimbursement at general practitioner (GP) and specialist levels. High-tech tools (artificial intelligence, smartphone apps, etc.) are providing exciting opportunities to identify high-risk individuals, self-screen, detect abnormalities in images, and assist with prescribing and treatment adherence. Better education is also needed, alongside provision of concise guidelines, enabling GPs to identify who would benefit from early initiation of renoprotective therapy; although, regardless of current renal function, cardiorenal protection is provided by SGLT2 inhibitor therapy.

Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood-brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods-such as intravenous, intrathecal, and intraparenchymal routes-and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD.

Adeno-associated virus vector hydrogel formulations for brain cancer gene therapy applications.

Gelatin-based formulations are utilized in neurosurgical procedures, with Medisponge® serving as an illustration of a secure and biocompatible hemostatic formulation. Noteworthy are combined hemostatic products that integrate pharmacological agents with gelatin. Gelatin matrices, which host biologically active substances, provide a platform for a variety of molecules. Biopolymers function as carriers for chemicals and genes, a facet particularly pertinent in brain cancer therapy, as gene therapy complement conventional approaches. The registration of Zolgensma underscores the efficacy of rAAV vectors in therapeutic gene delivery to the CNS. rAAVs, renowned for their safety, stability, and neuron-targeting capabilities, predominate in CNS gene therapy studies. The effectiveness of rAAV vector therapy varies based on the serotype and administration route. Local gene therapy employing hydrogel (e.g., post-tumor resection) enables the circumvention of the blood-brain barrier and restricts formulation diffusion. This study formulates gelatin rAAV gene formulations and evaluates vector transduction potential. Transduction efficiency was assessed using ex vivo mouse brains and in vitro cancer cell lines. In vitro, the transduction of rAAV vectors in gelatin matrices was quantified through qPCR, measuring the itr and Gfp expression. rAAVDJ and rAAV2 demonstrated superior transduction in ex vivo and in vitro models. Among the cell lines tested (Hs683, B16-F10, NIH:OVCAR-3), gelatin matrix F1 exhibited selective transduction, particularly with Hs683 human glioma cells, surpassing the performance Medisponge®. This research highlights the exploration of local brain cancer therapy, emphasizing the potential of gelatin as an rAAV vector carrier for gene therapy. The functional transduction activity of gelatin rAAV formulations is demonstrated.

Tight versus less tight 1-hour postprandial glycemic target in women with gestational diabetes mellitus - a single-center cohort study.

OBJECTIVES: We aimed to assess the impact of the change of 1-hour postprandial glycemic target from < 6.7 mmol/L (120 mg/dL) to < 7.8 mmol/L (140 mg/dL) on gestational diabetes mellitus (GDM) treatment and pregnancy outcomes. MATERIAL AND METHODS: In a retrospective analysis of 1021 GDM patients from the Department of Metabolic Diseases, University Hospital in Cracow, Poland, we compared insulin therapy regimens and pregnancy outcomes between women admitted in 2014-2016 (before the change) and in 2018-2019 (after it). RESULTS: A total of 377 patients were admitted between 2014 and 2016 (TIGHT group) and 644 between 2018 and 2019 (LESS TIGHT group). Women from the LESS TIGHT group were older (32 vs 30 years, p < 0.001) and gained less weight during pregnancy (7.0 vs 9.0 kg, p < 0.001). There was no change in the frequency of any insulin therapy (51.6% vs 56.1%, p = 0.168). In the LESS TIGHT group, the basal insulin-only model was used more frequently (32.5% vs 10.2%, p < 0.001), while the prandial insulin and basal-bolus model less frequently (23.6% vs 42.6% and 21.4% vs 36.7%, p < 0.001, respectively) than in the TIGHT group. There were no differences in the frequency of cesarean sections, preterm births, Hbd of delivery, mean birth weight or prevalence of perinatal complications. CONCLUSIONS: Less tight glycemic targets in women with GDM, compared to tighter targets, were associated with less frequent use of prandial insulin, with insulin therapy often limited to basal administration. The change in glycemic targets did not affect the prevalence of adverse pregnancy outcomes, providing evidence supporting new recommendations.

Expert Opinion on Optimising Type 2 Diabetes Treatment Using Fixed-Ratio Combination of Basal Insulin and GLP-1 RA for Treatment Intensification and Simplification.

The management of type 2 diabetes (T2D) often necessitates treatment intensification, and sometimes simplification to achieve glycaemic targets and mitigate complications. This expert opinion paper evaluates the use and positioning of the fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in optimising T2D management. On the basis of the evidence presented and discussions, these FRCs offer a promising approach for both treatment intensification and simplification in people with suboptimal glucose control despite receiving various therapies. In treatment intensification, FRCs provide a synergistic effect by addressing multiple pathophysiological defects contributing to hyperglycaemia. These FRCs effectively control both fasting and postprandial glucose (PPG) excursions, offering significantly improved glycaemic control with a lower hypoglycaemia risk and weight neutrality compared to traditional or complex insulin regimens. Moreover, the reduced injection frequency (once daily) and flexibility in the dosing schedule (with any major meal of the day) help mitigate patient resistance to insulin initiation or titration. This further reduces treatment burden, facilitating treatment adherence and enhancing patient convenience. These key benefits of FRCs over complex insulin regimens play a crucial role in long-term glycaemic management and overall treatment outcomes. Hence, the timely use of FRCs in the treatment algorithm for people with T2D represents a valuable strategy for optimising glycaemic control, addressing treatment barriers and enhancing patient-reported outcomes.

Excellence in the management of Advanced Hybrid Closed-Loop Systems: Lessons from the Polish cohort.

BACKGROUND: The aim of the study was to analyze the real-world performance of MiniMed 780G (MM780G) Advanced Hybrid Closed Loop (AHCL) system users from Poland (PL) and compare it to the European region excluding Poland (EU-PL) in order to identify factors contributing to potential differences. The former achieved some of the best Time in Range (TIR) results globally using this technology. METHODS: CareLink Personal data uploaded by MM780G system users from August 2020 to December 2022 were analyzed. RESULTS: The Polish users (N=1304) on average reached to TIR of 79.1 ±â€¯8.7 % (vs 73.0 ±â€¯10.0 % for EU-PL, N=55659), a TBR<54 mg/dL of 0.6 ±â€¯0.7 % (vs 0.4 ±â€¯0.6 %) and a TBR<70 mg/dL of 2.9 ±â€¯2.1 % (vs 2.1 ±â€¯1.8 %). The adoption rate of optimal settings (i.e, GT=100 mg/dL, AIT=2hr) in PL was high (19.7 % vs 6.3 %), and filtering on optimal setting users led to less pronounced differences in glycemic control between PL and EU-PL. A univariable analysis with post-AHCL TIR showed that geography itself (PL vs EU-PL) is not a significant contributor to a high post-AHCL TIR (p = 0.15), and that much of the Polish post-AHCL TIR can be explained by the high pre-AHCL TIR. CONCLUSION: The Polish MM780G users achieved better glycemic control than the general European population (excluding Poland). This is largely attributable to the adoption of optimal settings in Poland and the already high glycemic outcomes at system start. As these characteristics can be implemented elsewhere, we believe this outstanding result can be obtained in other countries as well.

Predicting acute kidney injury onset with a random forest algorithm using electronic medical records of COVID-19 patients: the CRACoV-AKI model.

INTRODUCTION: Acute kidney injury (AKI) is a serious and common complication of SARS­CoV­2 infection. Most risk assessment tools for AKI have been developed in the intensive care unit or in elderly populations. As the COVID­19 pandemic is transitioning into an endemic phase, there is an unmet need for prognostic scores tailored to the population of patients hospitalized for this disease. OBJECTIVES: We aimed to develop a robust predictive model for the occurrence of AKI in hospitalized patients with COVID­19. PATIENTS AND METHODS: Electronic medical records of all adult inpatients admitted between March 2020 and January 2022 were extracted from the database of a large, tertiary care center with a reference status in Lesser Poland. We screened 5806 patients with SARS­CoV­2 infection confirmed with a polymerase chain reaction test. After excluding individuals with lacking data on serum creatinine levels and those with a mild disease course (<7 days of inpatient care), a total of 4630 records were considered. Data were randomly split into training (n = 3462) and test (n = 1168) sets. A random forest model was tuned with feature engineering based on expert advice and metrics evaluated in nested cross­validation to reduce bias. RESULTS: Nested cross­validation yielded an area under the curve ranging between 0.793 and 0.807, and an average performance of 0.798. Model explanation techniques from a global perspective suggested that a need for respiratory support, chronic kidney disease, and procalcitonin concentration were among the most important variables in permutation tests. CONCLUSIONS: The CRACoV­AKI model enables AKI risk stratification among hospitalized patients with COVID­19. Machine learning-based tools may thus offer additional decision­making support for specialist providers.

Diabetes distress and diabetes burnout explored in various areas of life in patients with type 1 diabetes: effect of short-term psychological intervention.

INTRODUCTION: Diabetes distress (DD) and diabetes burnout (DB) are recognized psychological phenomena in patients with T1DM (type 1 diabetes mellitus). Still, there is an urgent need to create professional psychological intervention procedures to provide patients with adequate care. AIM: The aim of the study was to assess the level of DD and DB in T1DM patients at baseline and after 5 of sessions psychological intervention in the group of participants who applied for help. METHODS: 34 T1DM patients who requested psychological support (22 females, 12 males) and 30 patients in a control group (14 females, 16 males) participated in the study. At baseline clinical test results between groups were compared. Next, in the studied group measurements were repeated after a set of five psychological face-to-face individual interventions which lasted 30-60 min each. They were support sessions with elements of cognitive-behavioral interventions done by clinical psychologists. Session 1: introduction, interview and collection of test results; session 2-4: work on the indicated by the patient and test results most problematic aspect of diabetes, session 5: a summary and plan for further treatment if needed. The control group results were obtained only at baseline. Research tools: DDS; PAID, Diabetes Burnout test by Polonsky. RESULTS: At the baseline, significant differences were observed between the studied group and control group: in DB/DD levels: DB (3.9 ± 1.7 vs 2.4 ± 1.6; p < 0.001); DDS (3.2 ± 1.0 vs 2.7 ± 1.0; p = 0.064); PAID (62.3 ± 14.1vs 34.4 ± 21.0; p < 0.001). There were also group differences in HbA1c levels (8.7 ± 2.4 vs 7.3 ± 1.5; p = 0.028). After psychological interventions, there was a significant improvement in DB (3.9 ± 1.7vs 2.9 ± 1.2; p < 0.001; DDS (3.2 ± 1 vs 3.0 ± 0.7; p = 0.03); PAID (62.3 ± 14.1 vs 51.8 ± 12.5; p < 0.001). CONCLUSIONS: DD and DB constitute a significant problem in the group of T1DM patients, but providing appropriate specialist care may help them accept diabetes and improve life satisfaction, as well as regain control over their diabetes management.

Graphene Oxide (GO)-Based Bioink with Enhanced 3D Printability and Mechanical Properties for Tissue Engineering Applications.

Currently, a major challenge in material engineering is to develop a cell-safe biomaterial with significant utility in processing technology such as 3D bioprinting. The main goal of this work was to optimize the composition of a new graphene oxide (GO)-based bioink containing additional extracellular matrix (ECM) with unique properties that may find application in 3D bioprinting of biomimetic scaffolds. The experimental work evaluated functional properties such as viscosity and complex modulus, printability, mechanical strength, elasticity, degradation and absorbability, as well as biological properties such as cytotoxicity and cell response after exposure to a biomaterial. The findings demonstrated that the inclusion of GO had no substantial impact on the rheological properties and printability, but it did enhance the mechanical properties. This enhancement is crucial for the advancement of 3D scaffolds that are resilient to deformation and promote their utilization in tissue engineering investigations. Furthermore, GO-based hydrogels exhibited much greater swelling, absorbability and degradation compared to non-GO-based bioink. Additionally, these biomaterials showed lower cytotoxicity. Due to its properties, it is recommended to use bioink containing GO for bioprinting functional tissue models with the vascular system, e.g., for testing drugs or hard tissue models.

Education of adult type 1 diabetes patients in a diabetes ward setting: a best practice implementation project.

INTRODUCTION AND OBJECTIVES: Type 1 diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. Education is the cornerstone of effective diabetes care. In this implementation project, we aimed to improve compliance with best practices regarding type 1 diabetes educational interventions for adult hospitalized patients. METHODS: This project was guided by the JBI Evidence Implementation Framework. A baseline audit was conducted involving 20 nurses and 20 type 1 diabetes patients who received regular educational measures. Areas of non-compliance were identified and an improvement strategy was implemented. A follow-up audit was then conducted to evaluate the effectiveness of the improvement strategy. The project was conducted in Poland in 2021 in a tertiary referral unit that specializes in the diagnosis and treatment of diabetes. RESULTS: Substantial improvements were noted for all audit criteria after the implementation of strategies to address areas of non-compliance. Use of the education program improved from 0% to 100%. Compliance regarding patients receiving handouts and personalization of the program increased to 100%. We observed a significant improvement from 0% to 80% in the structuring of the program content. CONCLUSIONS: This project successfully improved the quality of education provided for type 1 diabetes patients in all relevant areas. We devised an education program, covering important aspects of diabetes education, with the patients reporting increased satisfaction with the personalized educational measures during their hospital stay. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A215.