Integrative attitudes of Ukrainian war refugees in two neighboring European countries (Poland and Hungary) in connection with posttraumatic stress symptoms and social support

Since February 24th, 2022, millions of Ukrainians have sought refuge in other, mainly European countries. Hungary, after Poland, is the second largest host of Ukrainian refugees. Only a portion of them are asylum seekers (~11.0% in Poland and ~ 1.1% in Hungary). The aim of the study is to compare the integrative acculturation attitudes between the war refugees residing in the two European countries. The comparison takes into account both the suffering of posttraumatic stress symptoms and social support. It is the first comparative study of this kind pertaining to the Ukrainian refugees in European countries. The data were obtained by a survey method using the modified CAPI (Computer Assisted Personal Interview) technique. The data analyzed were collected between November 21st and December 20th, 2022 from 728 adult Ukrainian individuals who crossed the borders of Poland and Hungary after February 24th, 2022. The research results show that refugees in Poland perceive significantly more social support and show stronger integrative attitudes than refugees in Hungary. The two samples do not differ regarding the presence of posttraumatic stress. The integrative attitudes proved not to be linked to gender and age, but linked to the host country. Besides social support and the host country, posttraumatic stress also proved to be a significant predictor of integrative attitudes

Therapeutic drug monitoring of posaconazole for effective prophylaxis of invasive fungal infections in pediatric patients: a pilot study

Introduction: Posaconazole, a second-generation triazole agent, is a drug with wide interindividual variation in bioavailability and variability of pharmacokinetics. The European Conference on Infections in Leukemia recommends the implementation of posaconazole therapeutic drug monitoring (TDM) in children to provide certainty regarding the efficacy of treatment and to increase its safety. A concentration of posaconazole in plasma in prophylactic regimens of above 0.7 mg/L is recommended. The aim of our pilot study was to discover the most effective method of posaconazole plasma concentration measurement, and to analyze posaconazole pharmacokinetics profiles in pediatric patients on posaconazole prophylaxis. Material and methods: Children receiving oncological treatment or hematopoietic stem cell transplantation in the Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology in Wroclaw Medical University Hospital were included in the trial. Posaconazole concentration was determined at the MonitLabTM laboratory using a newly validated high-performance liquid chromatography with fluorescence detector method. Results: Initial analysis shows that the major problem in patients on antifungal prophylaxis is inadequately low plasma drug concentration. Conclusions: Clinical trials on TDM of posaconazole should be developed

The Impact of High CMV Viral Load and Refractory CMV Infection on Pediatric HSCT Recipients with Underlying Non-Malignant Disorder

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for an increasing number of nonmalignant indications. Its use is restricted by severe transplant-related complications, including CMV infection; despite various prophylactic and therapeutic strategies, CMV reactivation has remarkable morbidity and mortality. The analysis included 94 children with nonmalignant disorder who underwent allogeneic HSCT in the Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation in Wrocław during years 2016–2020. Twenty-seven (29%) children presented with CMV infection, including ten (10/27; 37%) with high level CMV viremia (10,000 copies/mL). Six patients experienced subsequent CMV reactivation. The first-line ganciclovir-based (GCV) treatment was insufficient in 40% (11/27) of children. Overall survival (OS) was significantly lower in children with high CMV viremia compared to those with low levels/no CMV [1yrOS High CMV = 0.80 (95% CI 0.41–0.95) vs. 1yrOS others = 0.96 (95% CI 0.89–0.99)]. Similarly, patients with resistant and recurrent infections had greater risk of death. CMV reactivation at any level relevantly prolonged the hospital stay. CMV reactivation with high viremia load and resistant/recurrent CMV infections lead to a significant decrease in OS in children with nonmalignant disorders treated with HSCT. Our data proves there is an urgent need to introduce an effective anti-CMV prophylaxis in this cohort of patients

The Kinetics of Inflammation-Related Proteins and Cytokines in Children Undergoing CAR-T Cell Therapy—Are They Biomarkers of Therapy-Related Toxicities?

CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure

Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden

The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary

Neuroendocrine neoplasms of the small intestine and the appendix — update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita cienkiego i wyrostka robaczkowego — uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)]

Updated Polish recommendations for the management of patients with neuroendocrine neoplasms (NENs) of the small intestine (SINENs) and of the appendix (ANENs) are presented here. The small intestine, and especially the ileum, is one of the most common locations for these neoplasms. Most of them are well-differentiated and slow-growing tumours; uncommonly - neuroendocrine carcinomas. Their symptoms may be untypical and their diagnosis may be delayed or accidental. Najczęściej pierwszą manifestacją ANEN jest jego ostre zapalenie. Typical symptoms of carcinoid syndrome occur in approximately 20–30% of SINENs patients with distant metastases. In laboratory diagnostics the assessment of 5-hydroxyindoleacetic acid concentration is helpful in the diagnosis of carcinoid syndrome. The most commonly used imaging methods are ultrasound examination, computed tomography, magnetic resonance imaging, colonoscopy and somatostatin receptor imaging. Histopathological examination is crucial for the proper diagnosis and treatment of patients with SINENs and ANENs. The treatment of choice is a surgical procedure, either radical or palliative. Long-acting somatostatin analogues (SSAs) are essential in the medical treatment of functional and non-functional SINENs. In patients with SINENs, at the stage dissemination with progression during SSAs treatment, with high expression of somatostatin receptors, radioisotope therapy should be considered first followed by targeted therapies — everolimus. After the exhaustion of the above available therapies, chemotherapy may be considered in selected cases. Recommendations for patient monitoring are also presented.W artykule przedstawiono uaktualnione polskie zalecenia postępowania u chorych na nowotwory neuroendokrynne (NENs) jelita cienkiego (SINENs) i wyrostka robaczkowego (ANENs). Jelito cienkie, a w szczególności jelito kręte, należą do najczęstszych lokalizacji tych nowotworów. Są to w większości nowotwory wysokozróżnicowane i wolno rosnące, rzadko diagnozuje się raki neuroendokrynne. Ich objawy mogą być nietypowe, a rozpoznanie jest opóźnione albo przypadkowe. Najczęściej pierwszą manifestacją ANEN jest jego ostre zapalenie. Typowe objawy zespołu rakowiaka występują u około 20–30% pacjentów z SINENs z odległymi przerzutami. W diagnostyce laboratoryjnej najbardziej przydatne jest oznaczenie stężenia chromograniny A (CgA), badanie stężenia kwasu 5-hydroksyindolooctowego (5-HIAA) jest pomocne w diagnostyce zespołu rakowiaka. W obrazowaniu stosuje się najczęściej ultrasonografię (US), tomografię komputerową (CT), rezonans magnetyczny (MRI), kolonoskopię oraz obrazowanie receptorów somatostatynowych (SRI). Badanie histopatologiczne jest kluczowe dla właściwego rozpoznania i leczenia chorych z SINENs i ANENs. Leczeniem z wyboru jest postępowanie chirurgiczne, radykalne lub paliatywne. W leczeniu farmakologicznym czynnych i nieczynnych hormonalnie SINENs podstawowe znaczenie mają długodziałające analogi somatostatyny (SSAs). U chorych z SINENs w okresie uogólnienia z progresją w trakcie leczenia SSAs, z wysoką ekspresją receptorów po somatostatynowych w badaniu czynnościowym, należy rozważyć w pierwszej kolejności terapię radioligandową, a następnie terapie celowane z zastosowaniem ewerolimusu. W pracy przedstawiono także zalecenia dotyczące do monitorowania chorych