Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Potential cellular targets of platinum in the freshwater microalgae Chlamydomonas reinhardtii and Nitzschia palea revealed by transcriptomics.

Platinum group element levels have increased in natural aquatic environments in the last few decades, in particular as a consequence of the use of automobile catalytic converters on a global scale. Concentrations of Pt over tens of µg L-1 have been observed in rivers and effluents. This raises questions regarding its possible impacts on aquatic ecosystems, as Pt natural background concentrations are extremely low to undetectable. Primary producers, such as microalgae, are of great ecological importance, as they are at the base of the food web. The purpose of this work was to better understand the impact of Pt on a cellular level for freshwater unicellular algae. Two species with different characteristics, a green alga C. reinhardtii and a diatom N. palea, were studied. The bioaccumulation of Pt as well as its effect on growth were quantified. Moreover, the induction or repression factors of 16 specific genes were determined and allowed for the determination of possible intracellular effects and pathways of Pt. Both species seemed to be experiencing copper deficiency as suggested by inductions of genes linked to copper transporters. This is an indication that Pt might be internalized through the Cu(I) metabolic pathway. Moreover, Pt could possibly be excreted using an efflux pump. Other highlights include a concentration-dependent negative impact of Pt on mitochondrial metabolism for C. reinhardtii which is not observed for N. palea. These findings allowed for a better understanding of some of the possible impacts of Pt on freshwater primary producers, and also lay the foundations for the investigation of pathways for Pt entry at the base of the aquatic food web.

Reducing Antibiotic Duration for Uncomplicated UTI in the Pediatric Emergency Department.

BACKGROUND: Short-duration (3-5 days) antibiotic treatment of uncomplicated urinary tract infection (uUTI) in children >24 months of age is equivalent to longer-duration antibiotic treatment, with added benefits of antibiotic stewardship. At our pediatric emergency department (ED), 13% of 5- to 18-year-old patients discharged with uUTI received ≤5 days of antibiotics. We aimed to increase short-duration prescriptions in patients with uUTI from 13% to >50% over 12 months. METHODS: This quality improvement project was conducted from January 2021 to August 2022. Complicated UTI was excluded. Interventions included education, practice feedback, and electronic health record changes. The outcome measure, the proportion of children treated with a short antibiotic duration, was studied by using p-charts. Antibiotic days saved were calculated. Revisits with UTI within 14 days of confirmed uUTI treated with short-duration antibiotics (balancing measure) were analyzed by using Fisher's exact test. RESULTS: In 1292 (n = 363 baseline, 929 post-intervention) eligible patients treated for uUTI, shorter antibiotic duration increased from 13% to 91%. We met our 50% aim within 2 months, with continued improvement leading to an additional centerline shift. Consequently, 2619 antibiotic days were saved. Two of 334 (0.6%) patients returned (P = NS) within 14 days of the index visit with a culture-positive uUTI. CONCLUSIONS: By using education, feedback, and electronic health record changes, we decreased antibiotic duration in children discharged from the ED for uUTI without a significant increase in return visits with UTI. These interventions can be expanded to wider age groups and other outpatient settings.

How to detect non-institutionalized older patients at risk of malnutrition during their hospitalization? Comparison of 8 screening tools for malnutrition or nutritional risk.

BACKGROUND: The prevalence of malnutrition is high among the elderly population. Hospital admission is a window of opportunity for its detection. OBJECTIVE: To assess the concordance of different nutritional scales in hospitalized patients. METHODS: Prospective study in non-institutionalized patients over 65 years of age admitted to an internal medicine department. Five malnutrition screening surveys (MNA, MST, MUST, NRS-2000 and CONUT) and three nutritional risk screening surveys (SCREEN 3, 8 and 14) were compared. As gold standard we use the Global Malnutrition Leadership Initiative for Malnutrition (GLIM) definition of malnutrition. RESULTS: Eighty-five patients (37% female, median age 83 years) were included. Forty-eight percent (95% CI 38-59%) of patients were classified as malnourished according to GLIM criteria. The SCREEN 3 scale was the most sensitive (93%; 95% CI 87-98) and MUST the most specific (91%; CI 85-99). The most effective scale for excluding suspected malnutrition was SCREEN 3 (LR- 0.17; 95% CI 0.05-0.53) and the best for confirming it was MST (LR+ 7.08; 95% CI 3.06-16.39). Concordance between the different scales was low or very low with kappa indices between 0.082 and 0.465. CONCLUSIONS: A comprehensive approach is needed to detect malnutrition in hospitalized patients. More sensitive scales are more useful in initial screening. Nutritional risk tools could be effective at this stage. In a second step, malnutrition should be confirmed according to established criteria such as GLIM.

Ethics and artificial intelligence.

The relationship between ethics and artificial intelligence in medicine is a crucial and complex topic that falls within its broader context. Ethics in medical artificial intelligence (AI) involves ensuring that technologies are safe, fair, and respect patient privacy. This includes concerns about the accuracy of diagnoses provided by artificial intelligence, fairness in patient treatment, and protection of personal health data. Advances in artificial intelligence can significantly improve healthcare, from more accurate diagnoses to personalized treatments. However, it is essential that developments in medical artificial intelligence are carried out with strong ethical consideration, involving healthcare professionals, artificial intelligence experts, patients, and ethics specialists to guide and oversee their implementation. Finally, transparency in artificial intelligence algorithms and ongoing training for medical professionals are fundamental.

[Translated article] A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyse the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

Scabies in Spain: Trends in Public Interest and Ectoparasiticide Use. / Escabiosis en España: tendencias del interés público y consumo de ectoparasiticidas.

Scabies is an ectoparasitic dermatosis caused by the Sarcoptes scabiei var. hominis mite, which lives and reproduces in humans. Its incidence in Spain has increased in recent years. The aim of this study was to complement existing evidence on the increasing number of scabies cases in our country by analyzing changes in ectoparasiticide prescriptions and Internet searches for scabies infestations measured by Google Trends. We also examined correlations between these two variables. Our results show that public interest in scabies has increased in recent years and is positively and significantly correlated with an increasing use of ectoparasiticides. We believe that Google Trends should be considered as a complementary tool for monitoring real-time trends in scabies infestations in Spain.

[Translated article] Scabies in Spain: Trends in Public Interest and Ectoparasiticide Use.

Scabies is an ectoparasitic dermatosis caused by the Sarcoptes scabiei var. hominis mite, which lives and reproduces in humans. Its incidence in Spain has increased in recent years. The aim of this study was to complement existing evidence on the increasing number of scabies cases in our country by analyzing changes in ectoparasiticide prescriptions and Internet searches for scabies infestations measured by Google Trends. We also examined correlations between these two variables. Our results show that public interest in scabies has increased in recent years and is positively and significantly correlated with an increasing use of ectoparasiticides. We believe that Google Trends should be considered as a complementary tool for monitoring real-time trends in scabies infestations in Spain.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Wet chemical synthesis of TGA capped Ag2S nanoparticles and their use for fluorescence imaging and temperature sensing in living cells.

In this work, we describe a simple wet chemical route for preparing silver sulfide nanoparticles (Ag2S) encapsulated with thioglycolic acid (TGA). By using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), energy dispersive X-ray (EDS) microanalysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS), we have found that these nanoparticles were enrobed by TGA molecules and they have an Ag/S ratio nearly equal to 2.2 and a nearly spherical shape with two average size populations. Photoluminescence (PL) spectroscopy has shown that these nanoparticles are highly luminescent, photostable and photobleaching resistant and they emit in the first biologic window with a band peaking in the NIR region at 915 nm. We have demonstrated through a 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay protocol and using U-87 MG human living cells that these nanoparticles are biocompatible with a viability ratio higher than 80% for a concentration equal to 100 µg mL-1. By investigating the effect of pH, ionic strength and thermal quenching on the PL emission, we have shown that these nanoparticles provide a convenient stable tool to measure temperature in the biological range with a relative thermal sensitivity higher than 5% per °C and they may be used as suitable fluorescent probes for living cell imaging and intracellular temperature mapping.

Hospital surge capacity preparedness in disasters and emergencies: a systematic review.

BACKGROUND: Adequate and effective emergency preparedness for hospital surge capacity is a prerequisite to ensuring standard healthcare services for disaster victims. This study aimed to identify, review, and synthesize the preparedness activities for and the barriers to hospital surge capacity in disasters and emergencies. METHODS: We systematically searched seven databases (PubMed, MEDLINE, CINAHL, Scopus, Embase, Ovid, and PsycINFO). We included all English peer-reviewed studies published in January 2016 and July 2022 on surge capacity preparedness in hospital settings. Two independent researchers screened titles and abstracts, reviewed the full texts, and conducted data extractions using CADIMA software. We assessed the rigor of the included studies using the NIH quality assessment tools for quantitative studies, the Noyes et al. guidelines for qualitative studies, and the MMAT tool for mixed methods studies and summarized findings using the narrative synthesis method. We also used PRISMA reporting guidelines. RESULTS: From the 2560 studies identified, we finally include 13 peer-reviewed studies: 10 quantitative, one qualitative, and two mixed methods. Five studies were done in the USA, three in Iran (n = 3), and the remaining in Australia, Pakistan, Sweden, Taiwan, and Tanzania. The study identified various ways to increase hospital surge capacity preparedness in all four domains (staff, stuff, space, and system); among them, the use of the Hospital Medical Surge Preparedness Index and the Surge Simulation Tool for surge planning was noteworthy. Moreover, nine studies (69%) recognized several barriers to hospital surge capacity preparedness. CONCLUSION: The review provides synthesized evidence of contemporary literature on strategies for and barriers to hospital surge capacity preparedness. Despite the risk of selection bias due to the omission of gray literature, the study findings could help hospital authorities, public health workers, and policymakers to develop effective plans and programs for improving hospital surge capacity preparedness with actions, such as enhancing coordination, new or adapted flows of patients, disaster planning implementation, or the development of specific tools for surge capacity. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360332.

Modulating redox properties of solid-state ion-conducting materials using microwave irradiation.

The industrial adoption of low-carbon technologies and renewable electricity requires novel tools for electrifying unitary steps and efficient energy storage, such as the catalytic synthesis of valuable chemical carriers. The recently-discovered use of microwaves as an effective reducing agent of solid materials provides a novel framework to improve this chemical-conversion route, thanks to promoting oxygen-vacancy formation and O2-surface exchange at low temperatures. However, many efforts are still required to boost the redox properties and process efficiency. Here, we scrutinise the dynamics and the physicochemical dependencies governing microwave-induced redox transformations on solid-state ion-conducting materials. The reduction is triggered upon a material-dependent induction temperature, leading to a characteristically abrupt rise in electric conductivity. This work reveals that the released O2 yield strongly depends on the material's composition and can be tuned by controlling the gas-environment composition and the intensity of the microwave power. The reduction effect prevails at the grain surface level and, thus, amplifies for fine-grained materials, and this is ascribed to limitations in oxygen-vacancy diffusion across the grain compared to a microwave-enhanced surface evacuation. The precise cyclability and stability of the redox process will enable multiple applications like gas depuration, energy storage, or hydrogen generation in several industrial applications.

Impact of diabetes, malnutrition and sarcopenia on the prognosis of patients admitted to internal medicine.

OBJECTIVE: To describe patients hospitalized in internal medicine in terms of malnutrition and sarcopenia, depending on the presence or absence of type 2 diabetes mellitus (DM2), as well as to evaluate short- and long-term mortality related to both. METHODS: Cross-sectional, single-center study, which included consecutive patients admitted to internal medicine in May and October 2021. Malnutrition was determined using the Mini Nutritional Assessment-Short Form (MNA-SF) and sarcopenia using SARC-F and handgrip strength. Patients hospitalized for more than 48 h are excluded. RESULTS: 511 patients were analyzed, 49.1% male, mean age 75.2 +/- 15 years, 210 (41.1%) DM2. 6 groups (2 × 3 design) are generated based on the presence of DM2 and the nutritional status according to the result of the MNA-SF: 12-14 points, without risk; MNA-SF 8-12 points, high risk; MNA-SF 0-7 points, malnourished. Malnourished patients with DM2 had significantly higher sarcopenia, comorbidity, inflammation, and pressure ulcers. The main determinants of in-hospital mortality were sarcopenia (OR 1.27, 95%CI 1.06-1.54, p = 0.01), comorbidity (OR 1.27, 95%CI 1,08-1,49, p = 0.003) and inflammation (OR 1.01, 95%CI 1.00-1.02, p = 0.02). The 120-day prognosis was worse among malnourished patients (p = 0.042). CONCLUSION: Patients admitted with DM2 have a similar degree of malnutrition than the rest, but with greater sarcopenia. This sarcopenia, together with inflammation and comorbidity determine a worse prognosis. The active and early identification of malnutrition and sarcopenia and their subsequent approach could improve the prognosis of patients.

A systematic review of the literature: The use of metaphyseal sleeves in revision total knee arthroplasty. / Una revisión sistemática de la literatura: el uso de vainas metafisarias en cirugía de revisión de artroplastia de rodilla.

BACKGROUND AND OBJECTIVES: The purpose of this study is to analyze the indications, complications, survivorship and clinical/functional outcome of metaphyseal sleeves as a treatment option in revision total knee arthroplasty. MATERIAL AND METHOD: A systematic review was made following the PRISMA recommendations on the use of metaphyseal sleeves for revision total knee arthroplasty. We included prospective and retrospective studies published in the last 10 years looking at implant survivorship, clinical and functional outcome with a minimum follow-up of 2 years. RESULTS: The included studies showed good both functional and clinical outcomes. The overall reoperation rate was 16.2%, with an overall survival rate of 92.2% and aseptic survivorship of 98.2%. CONCLUSIONS: Metaphyseal sleeves are a good treatment option for this surgery, especially in AORI II or III type bone defects, achieving good intraoperative and primary stability of the implant, with good and rapid osseointegration.

Synthesis, characterization and thermoluminescence properties of MgB4O7 phosphor co-doped with Tm and Dy.

The luminescent and dosimetric properties of the MgB4O7 phosphor co-doped with Tm and Dy ions (MgB4O7:Tm,Dy) obtained by the solution combustion technique were investigated. With the prepared material, sintered dosimeters in pellet form were made. The MgB4O7 dosimeters doped with Tm and Dy with 0.25 and 0.10 mol% respectively and sintered at 1223 K for 3 h showed a sensitivity almost 11 times greater than the sensitivity of the TLD-100 commercial dosimeter. The TL response as a function of the gamma dose showed linearity up to 50 Gy followed by a supralinearity region and, above 500 Gy, the saturation region of the electron traps is reached. The fading of the main TL peak was negligible in the first five days after irradiation reaching 13% after 60 days and the lower detection limit was 43 µGy. The kinetic parameters were determined using the deconvolution method revealing general and second order kinetics. The morphology, crystallography and photoluminescence of the prepared phosphor samples are also reported.

Recommendations for the prevention of healthcare-associated infections in nursing homes.

Nursing homes (NH) conceptually should look as much like a home as possible. However NH have unquestionable similarities with a nosocomium as they are places where many patients with underlying diseases and comorbidities accumulate. There is evidence of transmission of microorganisms between residents and between residents and caregivers. We have not found any recommendations specifically aimed at the prevention of nosocomial infections in NH by the major Public Health Agencies and, therefore, the Health Sciences Foundation (Fundación de Ciencias de la Salud) has convened a series of experts and 14 Spanish scientific societies to discuss recommendations that could guide NH personnel in establishing written programs for the control and reduction of these infections. The present document is the result of these deliberations and contains suggestions for establishing such control programs on a voluntary and flexible basis in NH. We also hope that the document can help the health authorities to encourage this control activity in the different territorial areas of Spain. In our opinion, it is necessary to draw up a written plan and establish the figure of a coordinator or person responsible for implementing these projects. The document includes measures to be implemented and ways of quantifying the reality of different problems and of monitoring the impact of the measures established.

Inpatient management of diabetes and hyperglycaemia: an audit of Spanish hospitals.

OBJECTIVES: Evaluation of quality of care for patients with diabetes mellitus admitted to hospitals in Spain. METHODS: Cross-sectional study in one day that included 1193 (26.7%) patients with type 2 diabetes or hyperglycaemia out of a total of 4468 patients admitted to the internal medicine departments of 53 hospitals in Spain. We collected demographic data, adequacy of capillary glycaemic monitoring, treatment administered during admission, and recommended therapy at discharge. RESULTS: The median age of the patients was 80 years [74-87], of which 561 (47%) were women, with a Charlson index of 4 points [2-6], and 742 (65%) were fragile. Median blood glucose on admission was 155 mg/dl [119-213]. On the third day, the number of capillary blood glucose levels in target (80-180 mg/dl) at pre-breakfast was 792/1126 (70.3%), pre-lunch 601/1083 (55.4%), pre-dinner 591/1073 (55.0%), and at night 317/529 (59.9%). A total of 35 patients (0.9%) were suffering from hypoglycemia. Treatment during hospitalization was performed with sliding scale insulin in 352 (40.5%) patients, with basal insulin and rapid insulin analogues in 434 (50%), or with diet exclusively in 101 (9.1%). A total of 735 (61.6%) patients had a recent HbA1c value. At discharge, the use of SGLT2i increased significantly (30.1% vs. 21.6%; p < 0.001), as did the use of basal insulin (25.3% vs. 10.1%; p < 0.001). CONCLUSIONS: There is an excessive use of sliding scale insulin as well as insufficient information on HbA1c values and prescription upon discharge of treatments with cardiovascular benefit.

3D printing of PLA:CaP:GO scaffolds for bone tissue applications.

Graphene oxide (GO) has attracted increasing interest for biomedical applications owing to its outstanding properties such as high specific surface area, ability to bind functional molecules for therapeutic purposes and solubility, together with mechanical resistance and good thermal conductivity. The combination of GO with other biomaterials, such as calcium phosphate (CaP) and biodegradable polymers, presents a promising strategy for bone tissue engineering. Presently, the development of these advanced biomaterials benefits from the use of additive manufacturing techniques, such as 3D printing. In this study, we develop a 3D printed PLA:CaP:GO scaffold for bone tissue engineering. First, GO was characterised alone by XPS to determine its main bond contributions and C : O ratio. Secondly, we determined the GO dose which ensures the absence of toxicity, directly exposed in vitro (human osteoblast-like cells MG-63) and in vivo (zebrafish model). In addition, GO was microinjected in the zebrafish to evaluate its effect on immune cells, quantifying the genetic expression of the main markers. Results indicated that the GO tested (C : O of 2.14, 49.50% oxidised, main bonds: C-OH, C-O-C) in a dose ≤0.25 mg mL-1 promoted MG63 cells viability percentages above 70%, and in a dose ≤0.10 mg mL-1 resulted in the absence of toxicity in zebrafish embryos. The immune response evaluation reinforced this result. Finally, the optimised GO dose (0.10 mg mL-1) was combined with polylactic acid (PLA) and CaP to obtain a 3D printed PLA:CaP:GO scaffold. Physicochemical characterisation (SEM/EDS, XRD, FT-Raman, nano-indentation) was performed and in vivo tests confirmed its biocompatibility, enabling a novel approach for bone tissue-related applications.