A Rare Case of Methemoglobinemia after Ifosfamide Infusion in a 3-Year-Old Patient Treated for T-ALL.

Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids. Improving the general condition allowed for continuing chemotherapy without ifosfamide and completion of the HR2 block. Vigilance for methemoglobinemia as a very rare side effect should be widespread when using ifosfamide in the treatment protocols.

Anti-PD-1 Therapy in Advanced Pediatric Malignancies in Nationwide Study: Good Outcome in Skin Melanoma and Hodgkin Lymphoma.

BACKGROUND/AIM: The role of immune checkpoint inhibitors (ICIs; anti-PD1) in the treatment of childhood cancers is still evolving. The aim of this nationwide retrospective study was to assess the safety and effectiveness of ICIs used in a group of 42 patients, with a median age of 13.6 years, with various types of advanced malignancies treated in pediatric oncology centers in Poland between 2015 and 2023. RESULTS: The indications for treatment with anti-PD1 were as follows: Hodgkin lymphoma (11); malignant skin melanoma (9); neuroblastoma (8); and other malignancies (14). At the end of follow-up, complete remission (CR) was observed in 37.7% (15/42) of children and disease stabilization in 9.5% (4/42), with a mean survival 3.6 (95% CI = 2.6-4.6) years. The best survival (OS = 1.0) was observed in the group of patients with Hodgkin lymphoma. For malignant melanoma of the skin, neuroblastoma, and other rare malignancies, the estimated 3-year OS values were, respectively, 0.78, 0.33, and 0.25 (p = 0.002). The best progression-free survival value (0.78) was observed in the group with malignant melanoma. Significantly better effects of immunotherapy were confirmed in patients ≥ 14 years of age and good overall performance ECOG status. Severe adverse events were observed in 30.9% (13/42) patients.

Iron Overload in Children with Acute Lymphoblastic and Acute Myeloblastic Leukemia-Experience of One Center.

Transfusions of packed red blood cells (PRBCs), given due to an oncological disease and its acute complications, are an indispensable part of anticancer therapy. However, they can lead to post-transfusion iron overload. The study aim was to evaluate the role of ferritin as a nonspecific marker of leukemic growth and marker of transfusion-related iron overload. We performed a longitudinal study of PRBC transfusions and changes in ferritin concentrations during the oncological treatment of 135 patients with childhood acute lymphoblastic and acute myeloblastic leukemia (ALL and AML, median age 5.62 years). At the diagnosis, 41% of patients had a ferritin level over 500 ng/mL, and 14% of patients had a ferritin level over 1000 ng/mL. At the cessation of the treatment, 80% of the children had serum ferritin (SF) over 500 ng/mL, and 31% had SF over 1000 ng/mL. There was no significant difference between SF at the beginning of the treatment between ALL and AML patients, but children with AML finished treatment with statistically higher SF. AML patients had also statistically higher number of transfusions. We found statistically significant positive correlations between ferritin and age, and weight and units of transfused blood. Serum ferritin at the moment of diagnosis can be a useful marker of leukemic growth, but high levels of SF are connected with iron overload in both AML and ALL.

Significance of Th17 and Treg in Treatment Efficacy and Outcome in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia represents a malignant proliferation of lymphoid cells blocked at an early stage of cell differentiation. It is the most common cancer occurring in children. Despite favorable prognosis, the survival rate of patients with poor treatment response or relapse remains dismal. The interaction between leukemic cells and the tumor immune microenvironment is pivotal in mediating tumor progression. In this study we evaluated associations between Treg and Th17 lymphocytes and the clinical presentation of ALL pediatric patients to validate their value in monitoring treatment outcome. The peripheral blood and bone marrow aspirates from 35 pediatric patients with ALL and 48 healthy control subjects were selected for the experiment. We demonstrated the numbers of Th17 lymphocytes and Tregs were increased in the bone marrow of ALL patients at the moment of diagnosis compared to the healthy control group, with the latter significantly decreasing during the course of ALL treatment. Patients with lower Th17 were found to demonstrate higher risk of blasts prevalence in bone marrow at day 33. ALL patients with lower WBC demonstrated higher frequency of Tregs. In summary, we identified a significant role of Th17 and Treg lymphocytes in ALL of pediatric patients and their contribution to disease-related parameters.

Diagnostic Value and Prognostic Significance of Nucleated Red Blood Cells (NRBCs) in Selected Medical Conditions.

Nucleated red blood cells (NRBCs) are premature erythrocyte precursors that reside in the bone marrow of humans of all ages as an element of erythropoiesis. They rarely present in healthy adults' circulatory systems but can be found circulating in fetuses and neonates. An NRBC count is a cost-effective laboratory test that is currently rarely used in everyday clinical practice; it is mostly used in the diagnosis of hematological diseases/disorders relating to erythropoiesis, anemia, or hemolysis. However, according to several studies, it may be used as a biomarker in the diagnosis and clinical outcome prognosis of preterm infants or severely ill adult patients. This would allow for a quick diagnosis of life-threatening conditions and the prediction of a possible change in a patient's condition, especially in relation to patients in the intensive care unit. In this review, we sought to summarize the possible use of NRBCs as a prognostic marker in various disease entities. Research into the evaluation of the NRBCs in the pediatric population most often concerns neonatal hypoxia, the occurrence and consequences of asphyxia, and overall neonatal mortality. Among adults, NRBCs can be used to predict changes in clinical condition and mortality in critically ill patients, including those with sepsis, trauma, ARDS, acute pancreatitis, or severe cardiovascular disease.

Diagnostic yield of chest radiograph in management of adults with difficult-to-treat chronic cough-retrospective study.

Background: Chest radiograph (CXR) is a routine imaging test in adults with chronic cough (CC), while value of thoracic computed tomography (CT) in these patients is still a matter of discussion. The aims of the study were to assess the diagnostic yield of CXR and to evaluate the impact of thoracic CT on management of patients with difficult-to-treat CC referred to our cough clinic. Methods: The retrospective analysis of paired CXR and CT results was performed in 189 consecutive adults treated due to CC between 2015-2019 in our cough clinic. CC was defined as cough >8 weeks being the main or isolated ailment. The sensitivity, specificity, negative/positive predictive value (NPV, PPV) and diagnostic accuracy of CXR were calculated based on chest CT scan as the "gold standard". Only those CT scans which revealed abnormalities potentially related to CC and were associated with the changes in further diagnostic or therapeutic approach were construed as relevant CT findings during final analysis. Results: The median age of patients (male/female ratio 53/136) was 58 years (IQR 44-67), only 6 subjects (3.0%) were active smokers, median CC duration was 48 months (IQR 24-120). CXR revealed abnormal findings in 23/189 (12.2%) patients. Normal CXR was confirmed by CT in 141 subjects (141/166; 84.9%). In 25/166 (15.1%) patients, CT showed abnormalities that could explain the cause of CC and changed either the diagnostic protocol or therapy. In patients with abnormal CXR, CT confirmed abnormal findings in 8 cases (8/23, 34.8%). The sensitivity, specificity, PPV, NPV, diagnostic accuracy were 24.2%, 90.4%, 34.8%, 84.9% and 78.8%, respectively. Conclusions: CXR shows a limited diagnostic yield in adults with difficult-to-treat CC referred to cough clinic. Chest CT scan may add significant data impacting the diagnostic and therapeutic approach in these patients.

Diagnosing Lung Abnormalities Related to Heart Failure in Chest Radiogram, Lung Ultrasound and Thoracic Computed Tomography.

Heart failure (HF) is a multidisciplinary disease affecting almost 1-2% of the adult population worldwide. Symptoms most frequently reported by patients suffering from HF include dyspnoea, cough or exercise intolerance, which is equally often observed in many pulmonary diseases. The spectrum of lung changes related to HF is wide. The knowledge of different types of these abnormalities is essential to distinguish patients with HF from patients with lung diseases or both disorders and thus avoid unnecessary diagnostics or therapies. In this review, we aimed to summarise recent research concerning the spectrum of lung abnormalities related to HF in three frequently used lung imaging techniques: chest X-ray (CXR), lung ultrasound (LUS) and chest computed tomography (CT). We discussed the most prevalent abnormalities in the above-mentioned investigations in the context of consecutive pathophysiological stages identified in HF: (i) redistribution, (ii) interstitial oedema, and (iii) alveolar oedema. Finally, we compared the utility of these imaging tools in the clinical setting. In conclusion, we consider LUS the most useful and promising imaging technique due to its high sensitivity, repeatability and accessibility. However, the value of CXR and chest CT is their potential for establishing a differential diagnosis.

Parenchyma Sparing Anatomic Liver Resections (Bi- and Uni-Segmentectomies) for Liver Tumours in Children-A Single-Centre Experience.

Purpose: To present a single-centre experience in bi- and uni-segmentectomies for primary liver tumours in children. METHODS: This study included 23 patients that underwent (bi)segmentectomy. There were 15 malignant tumours (hepatoblastoma-13 patients), 7 benign tumours, and 1 calcifying nested stromal epithelial tumour. RESULTS: The median tumour diameter was 52 mm (range 15-170 mm). Bisegmentectomy 2-3 was most frequently performed (seven patients), followed by bisegmentectomy 5-6 (four patients). The median operative time was 225 min (range 95-643 min). Intraoperative complications occurred in two patients-small bowel perforation in one and an injury of the small peripheral bile duct resulting in biloma in the other. The median resection margin in patients with hepatoblastoma was 3 mm (range 1-15 mm). Microscopically negative margin status was achieved in 12 out of 13 patients. There were two recurrences. After a median follow-up time of 38 months (range 12-144 months), all 13 patients with HB were alive with no evidence of disease. Two relapsed patients were alive with no evidence of disease. CONCLUSIONS: From the available literature and data presented here, we propose that (bi)segmentectomy can become a viable surgical option in carefully selected paediatric patients and is sufficient to achieve a cure. Further studies evaluating the impact of parenchymal preservation surgery on surgical and oncological outcome should be conducted with a larger dataset.

Systemic inflammatory markers and serum lactate dehydrogenase predict survival in patients with Wilms tumour.

Introduction: Markers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been found to be associated with survival in cancer patients. The aim of the current study was to establish the prognostic significance of simple laboratory markers of systemic inflammation in paediatric patients diagnosed with Wilms tumour (WT). Additionally, we aimed to compare the complete blood count (CBC) parameters of WT patients and the non-oncological control group. Material and methods: The study group included 88 children diagnosed with WT. Clinicopathological data, as well as CBC, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at diagnosis, were obtained. Additionally, the laboratory results of 62 healthy control paediatric patients were collected. Uni- and multivariate proportional Cox's hazard analyses were computed to create a model predicting relapse-free survival (RFS) and overall survival (OS) in the study group. Results: High CRP, LDH, and NLR were associated with a higher stage of WT and shorter RFS, whereas all parameters correlated with OS. In multivariate analysis, only LDH levels had adverse significance in predicting RFS. C-reactive protein and LMR retained their prognostic value in the multivariate model predicting OS. Comparing the WT group with controls, high LDH, high CRP, high NLR, and high PLR were associated with WT presence. Conclusions: Preoperative LDH, CRP, NLR, PLR, and LMR have significant prognostic value in patients with WT independently of age and stage. Combined low CRP and high LMR identified the group of patients with excellent OS. Patients with high LDH were characterized by the highest risk of relapse.

Intravenous Immunoglobulin-Induced Aseptic Meningitis-A Narrative Review of the Diagnostic Process, Pathogenesis, Preventative Measures and Treatment.

Intravenous immunoglobulins (IVIGs) are widely used in the treatment of numerous diseases in both adult and pediatric populations. Higher doses of IVIGs usually serve as an immunomodulatory factor, common in therapy of children with immune thrombocytopenic purpura. Considering the broad range of IgG applications, the incidence of side effects in the course of treatment is inevitable. Aseptic meningitis, an uncommon but significant adverse reaction of IVIG therapy, can prove a diagnostic obstacle. As of April 2022, forty-four cases of intravenous immunoglobulin-induced aseptic meningitis have been reported in the English-language literature. This review aims to provide a thorough overview of the diagnostic process, pathophysiology, possible preventative measures and adequate treatment of IVIG-induced aseptic meningitis.

COVID-19 in pediatric cancer patients is associated with treatment interruptions but not with short-term mortality: a Polish national study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently constitutes the leading and overwhelming health issue worldwide. In comparison with adults, children present milder symptoms, with most having an asymptomatic course. We hypothesized that COVID-19 infection has a negative impact on the continuation of chemotherapy and increases nonrelapse mortality. MATERIAL AND METHODS: This study was performed to assess the course of SARS-CoV-2 among children with hematological or oncological malignancies and its impact on cancer therapy. Records of SARS-CoV-2 infection in 155 children with malignancies from 14 Polish centers for pediatric hematology and oncology were collected and analyzed. RESULTS: SARS-CoV-2 replication was observed in 155 patients. Forty-nine patients were symptomatic, with the following being the most common manifestations: fever (31 patients), gastrointestinal symptoms (10), coryza (13), cough (13) and headache (8). In children who were retested, the median time of a positive PCR result was 16 days (range 1-70 days), but 12.7% of patients were positive beyond day + 20. The length of viral PCR positivity correlated with the absolute neutrophil count at diagnosis. Seventy-six patients did not undergo further SARS-CoV-2 testing and were considered convalescents after completion of isolation. Antibiotic therapy was administered in 15 children, remdesivir in 6, convalescent plasma in 4, oxygen therapy in 3 (1-mechanical ventilation), steroids in 2, intravenous immunoglobulins in 2, and heparin in 4. Eighty patients were treated with chemotherapy within 30 days after SARS-CoV-2 infection diagnosis or were diagnosed with SARS-CoV-2 infection during 30 days of chemotherapy administration. Respiratory symptoms associated with COVID-19 and associated with oxygen therapy were present in 4 patients in the study population, and four deaths were recorded (2 due to COVID-19 and 2 due to progressive malignancy). The probability of 100-day overall survival was 97.3% (95% CI 92.9-99%). Delay in the next chemotherapy cycle occurred in 91 of 156 cases, with a median of 14 days (range 2-105 days). CONCLUSIONS: For the majority of pediatric cancer patients, SARS-CoV-2 infection does not result in a severe, life-threatening course. Our data show that interruptions in therapy are common and can result in suboptimal therapy.

Plasma free amino acid profiling as metabolomic diagnostic and prognostic biomarker in paediatric cancer patients: a follow-up study.

Amino acids (AAs) play a crucial role in cancer cell metabolism. Levels of 22 plasma AAs at the time of diagnosis and after treatment were established among 39 pediatric cancer patients and 33 healthy children. Glutamic acid levels decreased and tryptophan levels increased during treatment. Cancer patients presented significantly lower levels of glutamine and leucine post-treatment while levels of 12 other AAs were higher comparing to controls. Results suggest that plasma free AA profile may serve as a prognostic biomarker.

Characteristics of platelet indices and their prognostic significance in selected medical condition - a systematic review.

BACKGROUND: Platelets, also called thrombocytes, are produced in bone marrow and are the second most numerous blood cells which circulate in blood and play a pivotal role in hemostasis, wound healing, angiogenesis. There is a large body of evidence that platelets are likely to contribute to inflammation in multiple diseases. Also, recent studies revealed the association between platelet indices (PI) and inflammation. METHODS: PubMed, Scopus and Google Scholar databases were searched and only papers published in the last 10 years were consequently analyzed. RESULTS: The most frequently evaluated parameters are mean platelet volume (MPV), platelet diversity index (PDW), plateletcrit (PCT) and the presence of larger platelets (P-LCRs platelet larger cell ratio). The values of platelet indices (PI) were elevated in patients suffering from type 2 diabetes mellitus, myocardial infarction, cancers or acute surgical conditions, such as appendicitis. The measurement of PIs does not generate additional costs and can be performed during routine cell blood count, not requiring additional blood samples. CONCLUSIONS: Platelet indices may have prognostic and predictive value in numerous conditions.

Factors affecting weight and body composition in childhood cancer survivors-cross-sectional study.

Due to improved efficacy of antitumour treatment in the general population, there are increasingly more childhood cancer survivors. However, some of these survivors are at risk of distant complications including cardiovascular disease. We aimed to examine the risk of overweight/obesity and abnormal body composition in a large group of patients from our paediatric oncology centre. We used anthropometric methods and electrical bioimpedance to assess these features, and then determined their association with disease and treatment. We found patients treated for leukaemia/lymphoma (especially boys) had significantly higher rates of overweight/obesity compared to the other patient groups. On the contrary, overweight/obesity was more common in girls among patients treated for solid tumours. Patients treated for leukaemia/lymphoma were characterised by a higher body fat content compared to those treated for solid tumours and controls. During treatment for cancer, patients had a higher percentage of muscle mass deficiency compared to those in the control group. Our regression analysis showed time from completion of treatment, gender and type of therapy (radiotherapy, megachemotherapy) were associated with body weight and body composition including fat and muscle content. We recommend paediatricians and general practitioners should actively try to detect and prevent cardiovascular disease among childhood cancer survivors.

Determinants of utilization of cryopreservation of germ cells in adolescent cancer patients in four European countries.

Infertility is a relevant late-effect following cancer treatment; yet, a large proportion of survivors cannot recall having been informed of this risk. In an intervention study, we examined if and how supportive patient information material on fertility/fertility-preserving measures influences utilization of cryopreservation in adolescent cancer patients. The control group, recruited 03/2014-01/2016, received the usual patient education at initial diagnosis. The intervention group, recruited 04/2016-10/2017, received patient education supported by a fertility flyer and brochure. Patients and parents were each asked questions on utilization of cryopreservation in a questionnaire 3 and 6 months after initial diagnosis. Patient core and therapy data were obtained from medical records. Overall, cryopreservation rates showed no significant difference between the control (32.7%, n = 37/113) and intervention group (36.6%, n = 37/101). In the control group, cryopreservation was associated with gender (OR 0.100, CI 0.023-0.427), age (OR 1.559, CI 1.077-2.258) and recalling information on fertility protection (OR 33.663, CI 2.100-539.574); in the intervention group, cryopreservation was related to gender (OR 0.093, CI 0.026-0.330) and the estimated infertility risk (OR 43.665, CI 2.157-883.974).Conclusion: Cryopreservation rates did not overall increase following the intervention; however, the individual risk seemed to be brought into attention more: Those at risk, including younger patients, cryopreserved at higher rates.What is Known:•Infertility is a relevant late-effect following adolescent cancer.•Guidelines recommend to offer fertility protection before cancer treatment.•A relevant proportion of adolescents with cancer are not aware of this risk.•Fertility protection seems under-used in cancer patients at risk for infertility.What is New:•Information material on fertility and protection in adolescents did not increase overall rates of cryopreservation.•Cryopreservation rates were improved according to individual risk for infertility.•Our flyers and brochures on fertility in cancer patients are available in various languages.

The influence of different intensity of treatment on hormonal markers of gonadal function in acute lymphoblastic leukemia survivors.

Anti-cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti-Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed-up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.

Effectiveness comparison of various atrial fibrillation ablation methods in patients with common venous trunk.

BACKGROUND: Atrial fibrillation (AF) is a common clinical problem. The left atrium anatomy makes up a factor that may significantly affect the effectiveness of the AF ablation. OBJECTIVES: The aim of the study was to evaluate a long-term effectiveness ablation in patients with common pulmonary vein trunk (CPVT) and AF. MATERIAL AND METHODS: The outcomes of 129 procedures in 95 patients with CPVT out of 1,475 procedures carried out in 1,150 patients with AF treated with ablation, were analyzed. Ablation with CARTO 3 system (Johnson & Johnson, New Brunswick, USA), cryoballoon, and the circular multipolar duty-cycled radiofrequency-based pulmonary vein ablation producer with catheter (PVAC) were considered as advanced methods. The following data was recorded for every patient: age, gender, AF duration and type, previous antiarrhythmic drugs, weight, height, any prior cardioversion, and comorbidities, including hypertension, diabetes, hypothyreosis, thyrotoxicosis, heart failure, and stroke/transient ischemic attack. The following anatomical factors were assessed: the presence of patent foramen ovale (PFO) and localization of the CPVT on the basis of venography or computed tomography (CT). In the 1st year after ablation, 24-h Holter monitoring was performed 3-5 times, and the patients were encouraged to visit their doctor or an emergency department if a cardiac arrhythmia occurred. Long-term ablation effectiveness was assessed based on a telephone interview and patients' answers to the questionnaires including 12-lead electrocardiography (ECG). RESULTS: Sinus rhythm was maintained in 44 patients (43.6 %) after a median of 42 months (range 12-120). A lower number of clinical factors (odds ratio [OR] range 0.09; 95% confidence interval [CI] 0.02-0.56; p < 0.01), and advanced ablation methods (OR 3.1; 95% CI 1.4-7.1; p < 0.01) were related to a better longterm effectiveness. CONCLUSIONS: The long-term effectiveness of pulmonary vein (PV) isolation in patients with AF and CPVT is higher when advanced ablation techniques are used. Accumulation of clinical factors was found to be the most tremendous predictor of AF recurrence.

Is a normal chest radiograph sufficient to exclude pulmonary abnormalities potentially associated with chronic cough?

INTRODUCTION: There are few original studies on the true role of normal chest radiograph (CXR) in exclusion of pulmonary conditions that may be associated with chronic cough. Thus, the aim of the study was to assess whether a plain CXR is a sufficient tool to exclude relevant pulmonary causes of chronic cough. MATERIAL AND METHODS: A retrospective analysis of chest computed tomography (CT) scans in non-smoking patients with chronic cough and normal CXR was performed. The percentage of individuals in whom chest CT revealed relevant abnormalities was compared with the percentage of patients with irrelevant findings or normal chest CT scans. The negative predictive value (NPV) of the CXR in diagnosing the causes of chronic cough was calculated as a proportion of true negative CXRs (normal CXR AND irrelevant CT findings OR normal CT scan) to all negative CXRs (all patients, who had both a CXR and CT scan). RESULTS: The study group consisted of 59 adult patients with chronic cough, normal CXR and CT scan performed to diagnose the cause of chronic cough. In 21 patients (21/59, 36%), chest CT revealed abnormalities that were classified as relevant to chronic cough. The most frequent were: bronchiectasis (7/59, 11.9%), bronchial wall thickening (6/59, 10.2%) and mediastinal lymphadenopathy (5/59, 8.5%). The NPV of a CXR in diagnosing the causes of chronic cough was 64%. CONCLUSIONS: In conclusion, the NPV of CXR in diagnosing pulmonary causes of chronic cough is relatively low. Thus, plain CXR seems to be insufficient to exclude pulmonary diseases potentially associated with chronic cough.