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Cryopreservation and Validation of Microfragmented Adipose Tissue for Autologous Use in Knee Osteoarthritis Treatment
No full textMicro-fragmented adipose tissue (MFAT) is a promising autologous therapy for knee osteoarthritis. To avoid repeated liposuction procedures for its clinical application, MFAT obtained from patients with knee osteoarthritis was stored at −80 °C in a tissue bank. This study describes the preparation, cryopreservation, thawing, and washing, as well as comprehensive analysis of cell populations in fresh and MFAT thawed after two years. Immunophenotyping of both fresh and thawed MFAT showed a significant presence of endothelial progenitors and pericytes in the stromal vascular fraction. Viability before (59.75%) and after freezing (55.73%) showed no significant difference. However, the average cell count per gram of MFAT was significantly reduced in thawed samples (3.00 × 105) compared to fresh ones (5.64 × 105), likely due to processing steps. Thawed MFAT samples showed increased CD73 expression on the CD31highCD34high subset of EP and SA-ASC, as well as increased expression of CD105 on EP, the CD31lowCD34low subset of EP, pericytes, and SA-ASC. Microbiological testing confirmed 100% sterility, and double washing efficiently removed DMSO, confirming sample safety. Histological analysis revealed healthy, uniformly shaped adipocytes with intact membranes. This approach allows accurate estimation of cell yield for intra-articular injection, ensuring delivery of the target cell number into the knee. Quality control analysis confirms that cryopreserved MFAT retains high cellular and structural integrity, supporting its safety and suitability for clinical application
Clinical Features and Laboratory Findings of Hospitalized Children with Infectious Mononucleosis Caused by Epstein–Barr Virus from Croatia
No full textThe aim of this retrospective 6-year study was to analyze demographic, laboratory and clinical features of 212 patients (<18 years of age) with EBV-associated infectious mononucleosis (IM) hospitalized in a tertiary clinical care center in southeastern Europe and to identify possible predictors of complications. The median patient age was 14.7 years (IQR 7.7–16.5 years), with 59.4% of patients aged between 13 and 18 years. A total of 51.2% of patients were hospitalized within 7 days following the onset of symptoms (median duration of hospitalization was 9 days, IQR 7–11 days). The most common symptoms included fever (97.16%), tonsillitis (87.3%), lymphadenopathy (79.2%), hepatomegaly (77.4%) and splenomegaly (73.1%). Symptom distribution, maximal fever and fever duration did not differ among different age groups. The most common complications included tonsillar hypertrophy, thrombocytopenia, anemia, neutropenia and leukopenia but all patients showed favorable outcomes. Patients who developed three or more complications and those presenting with thrombocytopenia showed significantly longer hospitalization durations. Platelet count, bilirubin, ESR and AST were identified as the most accurate predictors of hospitalization duration using multiple linear regression analysis. Therefore, our results suggest that clinical assessment of individual patients remains the most reliable parameter for patient management and that laboratory findings play only a supporting role
Immunotherapy in mesothelioma – systematic review and meta-analysis of immunotherapy impact on OS and its correlation with PFS and ORR
No full textMesothelioma has a poor prognosis, with a 5-year overall survival (OS) rate less than 5%. Immunotherapy has been proven as a promising alternative to platinum-based therapies in first-line treatment. Our systematic literature search included 7 randomized clinical trials involving 2,549 patients to evaluate the impact of immunotherapy on OS across different lines of therapy, histologic subtypes, and ECOG performance status, and to assess the correlation between OS, progression-free survival (PFS), and objective response rate (ORR). Immunotherapy significantly improved OS (HR 0.78, P = 0.0005) with a similar benefit observed in first-line and second/later-line treatment (P = 0.25) as well as in all ECOG statuses (P = 0.32). A significantly greater benefit was observed in non-epithelioid compared to epithelioid mesothelioma (P = 0.002). Additionally, a strong correlation was shown only between OS and PFS (r = 0.86, P = 0.01). Our results emphasize the importance of immunotherapy in mesothelioma and further support PFS as a surrogate endpoint
The use of continuous glucose monitoring in people living with obesity, intermediate hyperglycemia or type 2 diabetes
No full textA global trend towards increased obesity, intermediate hyperglycemia (previously termed prediabetes) and type
2 diabetes, has prompted a range of international initiatives to proactively raise awareness and provide action-
driven recommendations to prevent and manage these linked disease states. One approach, that has shown
success in managing people already diagnosed with type 2 diabetes mellitus, is to use continuous glucose
monitoring (CGM) devices to help them manage their chronic condition through understanding and treating
their daily glucose fluctuations, in assocation with glucose-lowering medications, including insulin. However,
much of the burden of type 2 diabetes mellitus is founded in the delayed detection both of type 2 diabetes
mellitus itself, and the intermediate hyperglycemia that precedes it. In this review, we provide evidence that
using CGM technology in people at-risk of intermediate hyperglycemia or type 2 diabetes mellitus can signifi
cantly improve the rate and timin
Three-dimensional echocardiography in adults with congenital heart disease: a scientific statement of the European Society of Cardiology Working Group on Adult Congenital Heart Disease and the European Association of Cardiovascular Imaging of the European Society of Cardiology
No full textAbstract Congenital heart disease (CHD) is the most common inborn defect affecting up to 1% of newborns. The prevalence of CHD has shifted from childhood to adulthood, and the number of adult patients living with CHD continues to increase. This patient population presents unique challenges in diagnostic imaging and management due to complex underlying cardiac morphology, previous operations and interventions, and haemodynamic conditions. 3D echocardiography (3DE) has significantly improved our understanding of complex anatomic and haemodynamic substrates and emerged as a clinically useful tool that provides incremental information and complements the routine echocardiographic examination. The advantages of 3DE, including more accurate visualization of anatomic structures, absence of geometrical assumptions regarding shape of cardiac structures, and ability to obtain a complete view of the structures of interest from multiple perspectives in a beating heart, are especially relevant for diagnosis and follow-up of CHD in adult population, as well as interventional and surgical planning and guidance. In this scientific statement, we provide detailed and simple-to-follow descriptions of the added value of 3DE in evaluation of specific cardiac structures encountered in CHD, its role in diagnosis and follow-up, and training requirements for proficiency in 3DE in adult CHD
Efficacy, Toxicity and Effect of Pretreatment Cardiologic Consultation on Outcomes of Ibrutinib Therapy for Chronic Lymphocytic Leukemia—A KroHem Study
No full textBackground/Objectives: Ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia but has off-target side effects, most notably cardiac. In order to evaluate the efficacy and toxicity of ibrutinib treatment, risk factors for adverse outcomes and the influence of pretreatment cardiologic evaluation, KroHem collected data on Croatian patients with chronic lymphocytic leukemia treated with this drug. Methods: This is a retrospective survey performed in order to analyze the efficacy and toxicity of ibrutinib in a real-life setting. Patients starting therapy with ibrutinib for chronic lymphocytic leukemia between the time the drug became reimbursable in 2015 and 31 December 2021 were included, irrespective of treatment line. Results: We identified 436 patients fulfilling entry criteria; 404 (92.7%) responded to treatment. Cardiovascular side effects occurred in 25.0% of patients and hemorrhagic in 15.6%. The dose of ibrutinib was permanently reduced in 22.2% of patients. Median follow-up of the cohort was 29 months (IQR 18–41 months), estimated median overall survival 75 months (IQR 36 months–not reached), progression-free survival 54 months (IQR 24–81 months) and time on ibrutinib treatment 44 months (IQR 14–78 months). Factors significantly related to overall survival in multivariate analysis were stage, treatment line and age. Factors significantly related to progression-free survival in multivariate analysis were treatment line, age and pretreatment history or ECG finding of cardiac arrhythmia. Factors significantly related to time on ibrutinib treatment in multivariate analysis were age, pretreatment history or ECG finding of cardiac arrhythmia, and permanent dose reduction for toxicity. Sex, FISH and the presence of arterial hypertension were not independently significantly related to any of these outcomes. Pretreatment cardiologic consultation did not improve time on ibrutinib therapy, progression-free survival, overall survival, risk of stopping treatment due to cardiovascular side effects or risk of cardiovascular or sudden death, neither in the whole cohort nor in the subgroup of patients with and without pretreatment cardiac arrhythmia. Conclusions: Our analysis confirms the efficacy and tolerability of ibrutinib for the treatment of chronic lymphocytic leukemia. Patients older than 75 do significantly less well. Routine pretreatment cardiologic consultation does not improve outcomes and should not be considered part of standard pretreatment assessment without additional proof of its usefulness. Future investigations should aim at identifying predictive factors, mechanisms, and preventive strategies for reducing cardiotoxicity in chronic lymphocytic leukemia patients taking Bruton tyrosine kinase inhibitors
Effect of the Functional Appliances on Skeletal, Dentoalveolar, and Facial Soft Tissue Characteristics
No full textThis study aimed to evaluate the impact of Twin Block appliance therapy on skeletal, dentoalveolar, and facial soft tissue characteristics. The study included 18 participants with Class II skeletal malocclusion who were treated with the Twin Block appliance. Lateral cephalograms and 3D face scans were analyzed before and after therapy for each participant. Dependent t-test results showed a significant increase in the protrusion of the lower incisors (p < 0.001), proclination of the lower incisors (p = 0.021), SNB (p = 0.005), Ls:E (p = 0.040), mandibular length (p < 0.001), and soft tissue mandible length (p < 0.001) and a significant decrease in the ANB (p = 0.003), Wits (p = 0.001), ANPG (p = 0.001), and overbite (p = 0.001) and the retrusion of upper incisors (p = 0.002). Twin Block therapy caused changes in skeletal and soft tissue characteristics. The increase in the SNB angle and mandibular length, accompanied by the decrease in the ANB and Wits values reduced the skeletal discrepancy. The reduction in the ANPG indicated an improvement in the skeletal profile. Additionally, the increase in the soft tissue mandible length and distance between the upper lip and E-line contributed to improved esthetic soft tissue profile characteristics
BRAIN AND SPINAL CORD ORGANOIDS IN NEURODEGENERATIVE DISEASE RESEARCH
No full textOrganoidi mozga i leđne moždine predstavljaju inovativne trodimenzionalne stanične strukture dobivene iz ljudskih matičnih stanica koje vjerno oponašaju funkciju središnjeg živčanog sustava. U posljednjem desetljeću razvijeni su modeli za proučavanje neurodegenerativnih bolesti poput Alzheimerove bolesti, Parkinsonove bolesti i amiotrofične lateralne skleroze (ALS). Njihova sposobnost samorganizacije i diferencijacije u više tipova stanica, uključujući neurone i glija stanice, omogućuje bolje razumijevanje patoloških procesa, kao i testiranje novih potencijalnih terapija u uvjetima sličnima ljudskome organizmu. Organoidi mozga omogućuju stvaranje modela različitih regija mozga, poput korteksa ili srednjeg mozga, dok organoidi leđne moždine omogućuju stvaranje motoričkih neurona i analizu neuro-mišićne degeneracije. Unatoč brojnim prednostima, ova tehnologija i dalje ima neka određena ograničenja, kao što su nedostatak vaskularizacije, nedostatak imunoloških komponenti i ograničenje zrelosti stanica. Ipak, daljnjim razvojem i poboljšanjem funkcionalnosti organoida, otvara se mogućnost za precizniju personaliziranu medicinu i razvoj učinkovitijih terapija za neurodegenerativne bolesti.The organoids of the brain and spinal cord represent the innovative three -dimensional cellular structures obtained from human stem cells that faithfully mimic the function of the central nervous system. In the last decade, models for the study of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amiotrophic lateral sclerosis (ALS) have been developed. Their ability to self -organize and differentiation in multiple cell types, including neurons and glia cells, allows for a better understanding of pathological processes, as well as testing new potential therapies in conditions similar to the human body. Brain organoids allow models of different brain regions, such as a cortex or medium brain, while the organoids of the spinal cord allow the formation of motor neurons and analyzing neuro-muscular degeneration. Despite numerous advantages, this technology still has some certain restrictions, such as lack of vascularization, lack of immune components and restriction of cell maturity. However, with further development and improvement of organic functionality, there is an opportunity for more accurate personalized medicine and the development of more effective therapies for neurodegenerative diseases
Nutritional quality of tofu on the Croatian market
No full textTofu je biljni proizvod podrijetlom iz Kine koji se sve više konzumira kao zamjena za namirnice životinjskog podrijetla. Kvaliteta i nutritivna vrijednost soje kao i operacije u proizvodnom procesu (namakanje soje, dodatak učvršćivača, jačina prešanja, dimljenje, vrsta pakiranja) utječu na kvalitetu i nutritivnu vrijednost konačnog proizvoda. Nutritivna deklaracija obavezan je podatak na prehrambenim proizvodima, a Nutri-Score je jednostavna slikovna oznaka nutritivne kvalitete koja potrošačima može pomoći u donošenju informiranih odluka o kupnji. Cilj ovog istraživanja bio je analizirati i usporediti sastav i nutritivnu kvalitetu svježeg i dimljenog tofua te proizvoda od tofua dostupnih na hrvatskom tržištu. Istraživanje je provedeno analizom podataka s deklaracija 34 proizvoda u svrhu usporedbe i izračuna Nutri-Score vrijednosti. Utvrđeno je da tofu-proizvodi u usporedbi sa svježim i dimljenim tofuom imaju znatno raznolikiji sastav, statistički značajno veću energijsku vrijednost, veći udio masti, ugljikohidrata i soli. Zbog niske energijske vrijednosti, manjeg udjela soli, masti i šećera, svježi i dimljeni tofu imaju povoljnije Nutri-Score oznake (A, odnosno B) od tofu-proizvoda (oznaka C).Tofu is a plant-based product originating from China that is increasingly being consumed as a substitute for animal-based foods. The quality and nutritional value of soybeans, as well as the operations in the production process (soaking soybeans, addition of coagulants, pressing intensity, smoking, type of packaging), influence the quality and nutritional value of the final product. Nutritional labeling is mandatory on food products, and the Nutri-Score is a simple visual label of nutritional quality that can help consumers to make informed purchasing decisions. The aim of this study was to analyze and compare the composition and nutritional quality of fresh and smoked tofu, as well as tofu-based products available on the Croatian market. The research was conducted by analyzing data from the labels of 34 products to compare and calculate their Nutri-Score values. It was found that tofu-based products, in comparison to fresh and smoked tofu, have a significantly more varied composition, statistically higher energy value, and a greater proportion of fat, carbohydrates, and salt. Due to their lower energy value, and lower content of salt, fat, and sugar, fresh and smoked tofu have more favorable Nutri-Score ratings (A and B, respectively) compared to tofu-based products (rating C)