Search Results (13)

Background/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. Full article

Produced water is the waste aqueous phase from petroleum extraction. As it contains salts, a high organic load, and toxic organic compounds, it should be treated before disposal or reuse. In this research, the combination of membrane processes (microfiltration or membrane distillation) with TiO₂-based heterogeneous photocatalysis was assessed to treat synthetic produced water. Pre-treatment with both microfiltration and membrane distillation removed the majority (90–98%) of large organic compounds (humic acids) from produced water. Moreover, membrane distillation also eliminated salt (sodium chloride). However, membrane processes only removed 10–50% of phenol, used here as proxy for low-molecular-weight toxic organic compounds. For this reason, membrane permeates, from microfiltration and membrane distillation, underwent a further photocatalytic treatment aimed at phenol degradation. The application of TiO₂ photocatalysis to membrane distillation permeates was successful (100% phenol removal in 5 min), while the high chloride concentration of microfiltration permeates acted as inhibitor of the photocatalytic process. Overall, good-quality water may be obtained from the combination of membrane distillation and heterogeneous photocatalysis, which performed much better than the two techniques used separately. Indeed, while membrane distillation was not able to remove phenol, produced water was too complex a matrix to be effectively treated with TiO₂/UV photocatalysis alone. Full article

Background/Objectives: Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. Methods: This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. Results: Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil (p = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. Conclusions: The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks. Full article

Background and Objectives: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). Materials and Methods: This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023. Data on patient demographics, treatment regimens, and outcomes were collected and analysed using Kaplan–Meier survival curves and Cox proportional hazards models in R. The median age at ixazomib initiation was 66 years (range 40–91). Results: The overall response rate (ORR) was 65.8%, with 42% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 15.4 months, while median overall survival (OS) was 28.2 months. Hematologic toxicities included anaemia (53%), neutropenia (50%), and thrombocytopenia (45%). Infective complications, primarily COVID-19 and pneumonia, were reported in 38% of patients. The safety profile was consistent with previous studies, indicating manageable adverse events. Ixazomib-based therapy is effective and well tolerated in a real-world Croatian RRMM population. Conclusions: The findings align with clinical trial results, demonstrating the applicability of ixazomib in routine clinical practice. Further studies are needed to optimise treatment sequencing and improve patient outcomes. Full article

Patients with lymphoid malignancies are at increased risk of death or prolonged infection due to COVID-19. Data on the influence of different antineoplastic treatment modalities on outcomes are conflicting. Anti-CD20 monoclonal antibodies increase the risk of prolonged infection. It is unclear whether this risk is affected by the choice of the antibody (rituximab vs. obinutuzumab). To elucidate the role of antineoplastic therapy on COVID-19 outcomes, KroHem collected data on patients with lymphoid malignancies diagnosed with COVID-19 between October 2020 and April 2021. A total of 314 patients were identified, 75 untreated, 61 off treatment and 178 on treatment. The mortality rate in untreated and off-treatment patients was 15% and 16%; 9% and 10% had prolonged infection. In the on-treatment group, 3% were still prolonged positive at time of data collection, 62% recovered and 35% died; 42% had prolonged infection. Disease type, use of anti-CD20 monoclonal antibodies, prior autologous stem-cell transplantation (ASCT) and line of treatment did not significantly affect mortality. Mortality was higher in older patients (p = 0.0078) and those treated with purine analogues (p = 0.012). Prolonged COVID-19 was significantly more frequent in patients treated with anti-CD20 monoclonal antibodies (p = 0.012), especially obinutuzumab, and purine analogues (p = 0.012). Age, prior ASCT and treatment line did not significantly affect risk of prolonged infection. These data suggest that increased age and use of purine analogues are main risk factors for increased mortality of COVID-19 in patients with lymphoid malignancies. Obinutuzumab further increases the risk of prolonged disease, but not of death, in comparison to rituximab. Epidemiological considerations should be taken into account when choosing the appropriate antineoplastic therapy for patients with lymphoid malignancies. Full article

Background: Osteoarthritis (OA) is a progressive degenerative disease with an inflammatory background. Chronic myeloproliferative neoplasms (MPN) are clonal hematopoietic disorders characterized by chronic inflammation and a tendency for connective tissue remodeling. Aim: This study aimed to investigate the prevalence and associated risk factors of symptomatic OA (sOA) in MPN patients. Patients and methods: A total of 100 consecutive MPN (39 essential-thrombocythemia, 34 polycythemia-vera, 27 myelofibrosis) patients treated in two community hematologic centers were cross-sectionally evaluated. Patients were required to have both symptoms attributable to hip and/or knee OA and radiographic confirmation to be considered as having sOA. Results: The prevalence of hip and/or knee sOA was significantly higher among MPN patients than the previously reported prevalence in the general population of similar age (61% vs. 22%, p < 0.001). Hip sOA was present in 50%, knee sOA in 51% and sOA of both localizations in 41% of patients. A high proportion of MPN patients had radiographic signs of hip OA (94%) and knee OA (98%) in the presence of attributable symptoms. Among the other factors, sOA was univariately associated with the presence of JAK2 mutation, myelofibrosis phenotype, older age, higher body weight, and higher MPN-SAF score (p < 0.050 for all analyses). In the multivariate analysis, older age (odds ratio = 1.19, 95% confidence interval-CI 1.06–1.33) and higher body weight (OR = 1.15, 95% CI 1.06–1.25) were recognized as independent risk factors for sOA. On the other hand, cytoreductive treatment was a protective factor for sOA (OR = 0.07, 95% CI 0.006–0.86). Conclusions: The prevalence of sOA in MPN patients was higher than that in the general population and seems to correlate with older age, increased myeloproliferation and a higher inflammatory state. Whether cytoreductive treatment may postpone OA development in MPN patients warrants additional confirmation. Full article

This paper seeks to address the relation between semantics, pragmatics and the productivity of a low level lexico-grammatical construction, Have the N (body part/attitude) to ↔metapragmatic comment. The question posed is how semantics affects productivity, in the generative sense of extensibility of a construction (a form meaning pairing). The method identifies the specificity and variations of the Have the N (body part/attitude) to ↔metapragmatic comment construction within the pragmeme of politeness using the COHA. Hereafter, we consider how to measure the extensibility within the onomasiological frame based on the available pool of forms expressing an attitude/emotion, i.e., the coverage or attractivity of the Have the N to construction. The paper discusses the findings, namely, how to overcome methodological issues relating to a qualitative rather than quantitative approach to the constructional architecture and the relative productivity of constructions. The experimental small scale corpus study of Have the N to in the COHA suggests that a global view of constructional architecture at multiple levels should be pertinent to identifying the extensibility potential of the construction. Full article

Disease- and treatment-mediated immunodeficiency might render SARS-CoV-2 vaccines less effective in patients with hematologic diseases. We performed a prospective non-interventional study to evaluate humoral response after one and two doses of mRNA-1273, BNT162b2, or ChAdOx1 nCoV-19 vaccine in 118 patients with different malignant or non-malignant hematologic diseases from three Croatian treatment centers. An electrochemiluminescent assay was used to measure total anti-SARS-CoV-2 S-RBD antibody titers. After one vaccine dose, 20/66 (33%) achieved seropositivity with a median antibody titer of 6.1 U/mL. The response rate (58/90, 64.4%) and median antibody titer (>250 U/mL) were higher after two doses. Seropositivity varied with diagnosis (overall p < 0.001), with the lowest rates in lymphoma (34.6%) and chronic lymphocytic leukemia (52.5%). The overall response rate in chronic myeloproliferative neoplasms (CMPN) was 81.3% but reached 100% in chronic myeloid leukemia and other non-myelofibrosis CMPN. At univariable analysis, age > 67 years, non-Hodgkin’s lymphoma, active treatment, and anti-CD20 monoclonal antibody therapy increased the likelihood of no vaccine response, while hematopoietic stem cell recipients were more likely to respond. Age and anti-CD20 monoclonal antibody therapy remained associated with no response in a multivariable model. Patients with the hematologic disease have attenuated responses to SARS-CoV-2 vaccines, and significant variations in different disease subgroups warrant an individualized approach. Full article

Background: Advances in cancer therapy have dramatically improved outcomes for cancer pa-tients. However, cancer treatment can cause several cardiovascular (CV) complications, increasing cardiac mortality and morbidity in cancer patients and survivors. As a result, a new cardiology subspecialty—cardio-oncology (CO)—has been developed. The goals of CO are to understand the mechanism of the cardiotoxicity (CTX) of cancer therapies and invent the best monitoring and treatment strategies to improve the survival of cancer patients. Methods: We performed a retro-spective observational study reporting on the 6-year experience of the first CO service in Vilnius, Lithuania. Cancer patients were consulted by a single part-time specialist at Vilnius University Hospital. All new patients underwent blood tests, including cardiac biomarkers and advanced transthoracic echocardiogram (TTE) with stress protocol if indicated. During a follow-up, we evaluated the association of patient survival with such variables as age, gender, reasons for re-ferral, cancer location and stage, cardiovascular (CV) risk factors (RF), and rates and stage of CTX and treatment strategies. Results: 447 patients were consulted (70% females), and the median age was 64 years. Cardiovascular (CV) RF was common: 38.5% of patients had hypertension, almost 38% had dyslipidemia, 29% were obese, 10% were smokers, and 9% had diabetes. Nearly 26% of patients had a history of HF. Early biochemical cardiotoxicity was determined in 27%, early functional cardiotoxicity was seen in 17%, and early mixed cardiotoxicity—in 45% of referred patients treated with cardiotoxic cancer therapies. In addition, reduced left ventricular ejection fraction (LVEF) was found in 7% of patients. Beta-blockers (BB) were administered to 61.1% of patients, while angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) to 54.1% of patients. In addition, 18.3% of patients received loop diuretics and almost 12% mineralocorticoid receptor antagonists (MRA), respectively. A total of 143 patients died during the 6-year follow-up period. The leading cause of death was primarily cancer (92.3%). Only in 5.6% of patients, cardiovascular complications were reported as the cause of death, and 2.1% of deaths were due to the COVID–19 infection. We found that age (HR 1.020 [95% CI: (1.005–1.036)] p = 0.009); LV diastolic dysfunction (HR 1.731 [95% CI: 1.115–2.689] p = 0.015; NYHA stage II (HR 2.016 [95% CI: 1.242–3.272] p = 0.005; NYHA stage III (HR 3.545 [95% CI: 1.948–6.450] p < 0.001; kidney dysfunction (HR 2.085 [95% CI: 1.377–3.159] p = 0.001; previous cancer (HR 2.004 [95% CI: 1.219–3.295] p = 0.006); tumor progression (HR 1.853 [95% CI: 1.217–2.823] p = 0.004) and lung cancer (HR 2.907 [95%CI: 1.826–4.627] p < 0.001) were statistically significantly associated with the increased risk of all-cause death. Conclusions: CO is a rapidly growing subspecialty of cardiology that aims to remove cardiac disease as a barrier to effective cancer treatment by preventing and reversing cardiac damage caused by cancer therapies. Establishing a CO service requires a cardiologist with an interest in oncology. Continuous education, medical training, and clinical research are crucial to success. Age, previous cancer, tumor progression, kidney dysfunction, left ventricular diastolic dysfunction, and NYHA stages were associated with increased mortality. Full article

Diabetic foot ulcers (DFUs) caused by diabetes are prone to serious and persistent infections. If not treated properly, it will cause tissue necrosis or septicemia due to peripheral blood vessel embolism. Therefore, it is an urgent challenge to accelerate wound healing and reduce the risk of bacterial infection in patients. In clinical practice, DFUs mostly use hydrogel dressing to cover the surface of the affected area as an auxiliary treatment. Polyvinyl alcohol (PVA) is a hydrophilic hydrogel polymer widely used in dressings, drug delivery, and medical applications. However, due to its weak bioactivity and antibacterial ability, leads to limited application. Filler adding is a useful way to enhance the biocompatibility of PVA. In our study, cobalt-substituted hydroxyapatite (CoHA) powder was prepared by the electrochemically-deposited method. PVA and PVA-CoHA nanocomposite were prepared by the solvent casting method. The bioactivity of the PVA and composite was evaluated by immersed in simulated body fluid for 7 days. In addition, L929 cells and E. coli were used to evaluate the cytotoxicity and antibacterial tests of PVA and PVA-CoHA nanocomposite. The results show that the addition of CoHA increases the mechanical properties and biological activity of PVA. Biocompatibility evaluation showed no significant cytotoxicity of PVA-CoHA composite. In addition, a small amount of cobalt ion was released to the culture medium from the nanocomposite in the cell culture period and enhanced cell growth. The addition of CoHA also confirmed that it could inhibit the growth of E. coli. PVA-CoHA composite may have potential applications in diabetic trauma healing and wound dressing. Full article

Calcium ions and phosphate ions are usually present in biological organisms and human bodies. Different ratios of calcium to phosphorus result in different types of calcium-to-phosphorus crystals. Hydroxyapatite (HA) is the main component of human hard bony tissues. It has good biocompatibility and is often used in bone repair. With the addition of cobalt ions, it can act as a hypoxia-inducing factor to accelerate the regeneration of hard bony tissues. At present, the laser-assisted biomimetic (LAB) method can very quickly deposit calcium phosphate coatings, which can be used on polymer and titanium surfaces. In this study, we first used anodization treatment (with TiO₂ nanotubes (TNTs)), alkali treatment (with NaOH), and acid treatment (with HCl) to form nanopore structures on titanium surfaces in the laboratory. Subsequently, LAB treatment was used to deposit calcium phosphate and cobalt-substituted hydroxyapatite onto titanium pieces with different surface treatments. The results showed that smaller holes resulted in better deposition (TNTs), and controlling the pH value in the solution changed the crystal morphology. LAB treatment imbued the titanium surface with super-hydrophilic properties and improved biocompatibility. A human osteoblast cell line (MG-63) used for the cell viability test showed that LAB treatment can improve cell growth. In particular, TNT-CoHA (cobalt-substituted hydroxyapatite) cells grew the best. Immersion in simulated bodily fluid confirmed that LAB treatment with a CoHA solution improved the hydrophilicity, biocompatibility, and bioactivity of titanium surfaces. It is hoped that this study provides useful information for surface coating of biomedical materials in the future. Full article

Magnetic nanoparticles are used to enhance the image contrast of magnetic resonance imaging (MRI). However, the development of magnetic nanoparticles with a low dose/high image contrast and non-toxicity is currently a major challenge. In this study, cobalt-substituted hydroxyapatite nanoparticles deposited on titanium (Ti-CoHA) and cobalt-substituted hydroxyapatite nanoparticles deposited on titanium dioxide nanotubes (TNT-CoHA) were synthesized by the electrochemical deposition method. The particle sizes of Ti-CoHA and TNT-CoHA were 418.6 nm and 127.5 nm, respectively, as observed using FE-SEM. It was shown that CoHA can be obtained with a smaller particle size using a titanium dioxide nanotube (TNT) electrode plate. However, the particle size of TNT-CoHA is smaller than that of Ti-CoHA. The crystal size of the internal cobalt oxide of CoHA was calculated by using an XRD pattern. The results indicate that the crystal size of cobalt oxide in TNT-CoHA is larger than that of the cobalt oxide in Ti-CoHA. The larger crystal size of the cobalt oxide in TNT-CoHA makes the saturation magnetization (Ms) of TNT-CoHA 12.6 times higher than that of Ti-CoHA. The contrast in MRIs is related to the magnetic properties of the particles. Therefore, TNT-CoHA has good image contrast at low concentrations in T₂ images. The relaxivity coefficient of the CoHA was higher for TNT-CoHA (340.3 mM⁻¹s⁻¹) than Ti-CoHA (211.7 mM⁻¹s⁻¹), and both were higher than the commercial iron nanoparticles (103.0 mM⁻¹s⁻¹). We showed that the TNT substrate caused an increase in the size of the cobalt oxide crystal of TNT-CoHA, thus effectively improving the magnetic field strength and MRI image recognition. It was also shown that the relaxivity coefficient rose with the Ms. Evaluation of biocompatibility of CoHA using human osteosarcoma cells (MG63) indicated no toxic effects. On the other hand, CoHA had an excellent antibacterial effect, as shown by E. coli evaluation, and the effect of TNT-CoHA powder was higher than that of Ti-CoHA powder. In summary, TNT-CoHA deposited electrochemically on the TNT substrates can be considered as a potential candidate for the application as an MRI contrast agent. This paper is a comparative study of how different electrode plates affect the magnetic and MRI image contrast of cobalt-substituted hydroxyapatite (CoHA) nanomaterials. Full article

Hydroxyapatite has excellent biocompatibility and osteo-conductivity and, as the main inorganic component of human bones and teeth, is commonly used for bone repair. Its original characteristics can be changed by metal ion substitution. Cobalt ions can act as hypoxia-inducible factors and accelerate bone repair. At the same time, cobalt has paramagnetic properties and is often used in the study of medical imaging and target drugs. Through the introduction of cobalt ions, the unique hydroxyapatite has better biological activity and positioning of medical images. Herein, cobalt-substituted hydroxyapatite (CoHA) was synthesized on the surface of a titanium plate by electrochemical deposition and changes in the power output mode to explore the impact on CoHA. Electrochemical deposition with a pulse current significantly improved the productivity and uniformity of CoHA on the surface of titanium. CoHA show paramagnetic characteristics by a superconducting quantum interference device (SQUID). Resulting smaller particle size and circular morphology improves the magnetic strength of CoHA. Magnetic resonance imaging (MRI) of CoHA showed significant image contrast effect at low concentrations. The calculated particle relaxation rate was higher than other common MRI contrast agents. Biocompatibility of CoHA powder was evaluated using the human osteosarcoma cell line (MG63) which confirmed that CoHA is not cytotoxic and can promote cell growth and extracellular matrix mineralization. With the release of cobalt ions, CoHA was found to be significantly good in repression E. coli indicating about than 95% reduction in bacterial growth. The as-synthesized CoHA has a low degree of crystallinity, highly sensitive image contrast effect, and good bioactivity, and may have potential applications in bone repair and MRI. Full article