Granulocyte transfusions in life-threatening infections of children with hemato-oncological diseases.

Granulocytes are the most important cells for host defense during infections. Granulocyte suspension transfusions (GTx) may be given as additional treatment in severely neutropenic patients with life-threatening infections when antimicrobial therapy is inadequate. The aim of this study was to evaluate the effectiveness and safety of GTx for the treatment of children with hemato-oncological disease, febrile neutropenia and serious life-threatening infections. Patients who underwent GTx between July 2020 and September 2022 were evaluated retrospectively. Hematologic and clinical response rates, adverse effects, characteristics of infection episodes and survival data of the patients were analyzed. During the study period, 60 patients received a total of 313 GTx for 81 infection episodes with a median number of GTx/infection episode of 3 (range 1-29). The median neutrophil count per bag was 20.8 (range 7.9-68.3) × 109 and the median neutrophil count per kg body weight was 0.82 (range 0.17-9.2) × 109. Clinical response was 85 %. Clinical response decreased significantly as the duration of neutropenia increased (p = 0.002). Hematologic response was calculated in 198 GTx (GTx given with pre-transfusion neutrophil count ≤ 0.5 × 109/L); hematologic response rate was 34 %. The infection-related mortality was 15 % and overall survival rate was 87 % and 70 % on days 30 and 90, respectively. No serious side effects were observed in any patient. Granulocyte transfusions appear to be safe and effective supportive treatment in neutropenic children with hematologic/oncologic diseases and severe infections.

Fat Matters: Exploring Cancer Risk through the Lens of Computed Tomography and Visceral Adiposity.

Obesity is an established risk factor for cancer. However, conventional measures like body mass index lack precision in assessing specific tissue quantities, particularly of the two primary abdominal fat compartments, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Computed tomography (CT) stands as the gold standard for precisely quantifying diverse tissue types. VAT, distinguished by heightened hormonal and metabolic activity, plays a pivotal role in obesity-related tumor development. Excessive VAT is linked to aberrant secretion of adipokines, proinflammatory cytokines, and growth factors, fostering the carcinogenesis of obesity-related tumors. Accurate quantification of abdominal fat compartments is crucial for understanding VAT as an oncological risk factor. The purpose of the present research is to elucidate the role of CT, performed for staging purposes, in assessing VAT (quantity and distribution) as a critical factor in the oncogenesis of obesity-related tumors. In the field of precision medicine, this work takes on considerable importance, as quantifying VAT in oncological patients becomes fundamental in understanding the influence of VAT on cancer development-the potential "phenotypic expression" of excessive VAT accumulation. Previous studies analyzed in this research showed that VAT is a risk factor for clear cell renal cell carcinoma, non-clear cell renal cell carcinoma, prostate cancer, and hepatocarcinoma recurrence. Further studies will need to quantify VAT in other oncological diseases with specific mutations or gene expressions, in order to investigate the relationship of VAT with tumor genomics.

Lung and blood perioperative metalloproteinases in patients undergoing oncologic lung surgery: Prognostic implications.

BACKGROUND: Metalloproteinases (MMPs) have been reported to be related to oncologic outcomes. The main goal of the study was to study the relationship between these proteins and the long-term prognosis of patients undergoing oncologic lung resection surgery. METHODS: This was a substudy of the phase IV randomized control trial (NCT02168751). We analyzed MMP-2, -3, -7, and -9 in blood samples and bronchoalveolar lavage (LBA) and the relationship between MMPs and long postoperative outcomes (survival and disease-free time of oncologic recurrence). RESULTS: Survival was longer in patients who had lower MMP-2 levels than those with higher MMP-2 in blood samples taken 6 h after surgery (6.8 vs. 5.22 years; p = 0.012) and MMP-3 (6.82 vs. 5.35 years; p = 0.03). In contrast, survival was longer when MMP-3 levels were higher in LBA from oncologic lung patients than those with lower MMP-3 (7.96 vs. 6.02 years; p = 0.005). Recurrence-free time was longer in patients who had lower MMP-3 levels in blood samples versus higher (5.97 vs. 4.23 years; p = 0.034) as well as lower MMP-7 (5.96 vs. 4.5 years; p = 0.041) or lower MMP-9 in LBA samples (6.21 vs. 4.18 years; p = 0.012). CONCLUSION: MMPs were monitored during the perioperative period of oncologic lung resection surgery. These biomarkers were associated with mortality and recurrence-free time. The role of the different MMPs analyzed during the study do not have the same prognostic implications after this kind of surgery.

[The design of research project of behavioral strategies of women with breast cancer experience].

The breast cancer can be successfully cured after its early diagnosis. Nevertheless, this disease remains one of the main causes of female mortality in Russia and in the world. The effective mode of overcoming this disease is to intensify institutional programs of prevention and treatment in context of the national health care system. The efficacy of such programs depends on social economic inequality and differences between population groups with respect to informational, financial and regional aspects. The study design includes: comprehensive approach to analysis of social economic and infrastructural conditions of organization of prevention and treatment of breast cancer; of characteristics of symbolic filling of the breast cancer phenomenon in the Russian society; of factors determining willingness and ability of women of different social status groups to be involved in prevention and treatment of breast cancer and conditions, including conditions of increasing their subjectness.

Assessment of female fertility preservation in Auvergne 3 years after implementation of the PREFERA platform (PREservation FERtilité Auvergne).

INTRODUCTION: Fertility preservation (FP) in patients with cancer or pathology at risk of gonadotoxicity is now according to legislation, an integral part of the treatment protocol. for this reason, clinical-biological platforms have emerged with the aim of developing and improving this practice, such as the PREFERA platform (PREservation FERtilité Auvergne) MATERIAL ET METHOD: This is an observational cohort study to evaluate female fertility preservation activity in Auvergne at the AMP-CECOS center of the Clermont-Ferrand University Hospital from March 2013 to March 2019. This period covering 3 years before and after the creation of PREFERA in 2015. RESULTS: 205 patients were referred for fertility preservation consultations, including 77 before the platform was set up and 128 after, corresponding to an increase of 66%. 190 patients (92.7%) referred were eligible for FP, of whom 169 (88.9%) received treatment. Thirty-nine patients underwent oocyte vitrification before the platform was set up and 74 after (+89.7%), twenty patients underwent ovarian cortex freezing before the platform was set up and 27 after (+35%). Only 54 patients (26.2%) were seen for follow-up with an increased number of consultations following the implementation of PREFERA. (8% vs 33%, p<0.001). CONCLUSION: Creation of the PREFERA platform facilitated patient access and management of fertility preservation procedures. However, at the regional level, it is necessary to continue to raise awareness of fertility issues, particularly in the context of post-cancer follow-up, both among patients and health professionals.

Social factors influence the course and prognosis of malignat diseases.

BACKGROUND: A statement of the dia-gnosis of malignant disease fundamentally changes the identity of a man. A healthy person changes to a patient. A lot of studies analyzed the influence of marital status on the disease development. PURPOSE: We present an analysis of interpersonal relationships in connection with oncological diseases. The majority of the authors consider living in a couple as a positive prognostic factor. On the other hand, malignant disease at a younger age increases the risk of divorce or breakup.

[The comparative analysis of coefficients of variation of standard regional indices of mortality and causes having and having not accurate criteria of diagnostics].

The standardized mortality coefficients for different causes have significant variability between regions and depend on many factors. The purpose of study was to investigate interregional variation coefficients of standardized mortality of oncologic diseases as compared with other causes having no explicit diagnosis criteria. The 49 death causes were selected out of 295 causes of the Short nomenclature of the Rosstat. These causes were distributed by 2 groups: neoplasms and causes without explicit diagnostic criteria. The standard mortality indicator was calculated on the basis of the European standard. The significance of differentiations between the groups was estimated using one-factor dispersion analysis by pair comparison and Bonferroni amendment. The level of interregional variation coefficient of the standard mortality indicator from cancer was lower than from other causes with no explicit diagnostic criteria. Even the reasons of death from oncologic diseases which has no explicit criteria have the significantly less marked variation coefficient as compared to other two groups. There were reliable differences of the variation coefficients between the subgroup of oncologic diseases with precise location of tumor and the subgroup of oncologic diseases of other and non-explicit locations. The death causes due to "other diseases" and the death causes due to diseases with no-explicit diagnostic criteria had similarly high level of variation coefficient. The difference of the regional standard mortality indicator of concrete reasons is affected by uncoordinated criteria of diseases diagnostic and the main reason of death determination. The letter of the Minzdrav of Russia concerning the rules of application of notion "senility" as cause of death played certain role also. The different level of morbidity in regions had the influence as well. The harmonization of verification of all the cases of diagnosis, its "depth" and applied criteria is needed for proper analysis of data of death from separate causes is needed.

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation.

We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT). The patients consisted of 20 males and 9 females with a median age of 14.5 years (age range, 3 to 18 years) and a median body weight of 47 kg (body weight range, 15 to 80 kg). ISA was used as prophylaxis in 5 patients and as treatment in 24 cases (20 after therapeutic failure, 4 as first-line therapy). According to European Organization for Research and Treatment of Cancer (EORTC) criteria, we registered 5 patients with proven IFD, 9 patients with probable IFD, and 10 patients with possible IFD. Patients with a body weight of <30 kg received half the ISA dose; the others received ISA on the adult schedule (a 200-mg loading dose every 8 h on days 1 and 2 and a 200-mg/day maintenance dose); for all but 10 patients, the route of administration switched from the intravenous route to the oral route during treatment. ISA was administered for a median of 75.5 days (range, 6 to 523 days). The overall response rate was 70.8%; 12 patients with IFD achieved complete remission, 5 achieved partial remission, 5 achieved progression, and 3 achieved stable IFD. No breakthrough infections were registered. PK monitoring of 17 patients revealed a median ISA steady-state trough concentration of 4.91 mg/liter (range, 2.15 to 8.54 mg/liter) and a concentration/dose (in kilograms) ratio of 1.13 (range, 0.47 to 3.42). Determination of the 12-h PK profile was performed in 6 cases. The median area under the concentration-time curve from 0 to 12 h was 153.16 mg·h/liter (range, 86.31 to 169.45 mg·h/liter). Common Terminology Criteria for Adverse Events grade 1 to 3 toxicity (increased transaminase and/or creatinine levels) was observed in 6 patients, with no drug-drug interactions being seen in patients receiving immunosuppressants. Isavuconazole may be useful and safe in children with hemato-oncologic diseases, even in the HSCT setting. Prospective studies are warranted.

Acute portal vein thrombosis in noncirrhotic patients - different prognoses based on presence of inflammatory markers: a long-term multicenter retrospective analysis.

Background: Portal vein thrombosis (PVT) is a partial or complete thrombotic occlusion of the portal vein and is rare in noncirrhotic patients.Patients and methods: 78 adult patients with noncirrhotic acute PVT without known malignity were evaluated. Patients with initial CRP level 61-149 mg/l were excluded.Results: Patients were divided into two groups - the first one (33 patients) was characterized with signs of inflammation and CRP over 149 mg/l. The second group (45 patients) was without signs of inflammation and CRP level less than 61 mg/l. The frequency of prothrombotic hematologic factors was statistically significantly different in levels of factor VIII and MTHFR 677 C mutation. All patients from both groups underwent the same oncologic and hemato-oncologic screening which was positive in 23 patients (51.1%) in the group without signs of inflammation. In the group of patients with clinical and laboratory signs of inflammation oncologic and hemato-oncologic screening was positive only in 1 patient (3.0%). Complete portal vein recanalization was achieved in 19.2%, partial recanalization in 26.9%.Conclusions: Patients with clinical signs of inflammation and acute PVT have a low risk of malignancy in contrast to patients without signs of inflammation and acute PVT, which have a high risk of oncologic or hemato-oncologic disease. Patients with negative hemato-oncologic screening should be carefully observed over time because we expect they are at higher risk for the development of hemato-oncologic disease, independent from the presence and number of procoagulation risk factors.

Predictors of mortality after admission to pediatric intensive care unit in oncohematologic patients without history of hematopoietic stem cell transplantation: A single-center experience.

BACKGROUND: Pediatric oncohematologic patients are a high-risk population for clinical deterioration that might require pediatric intensive care unit (PICU) admission. Several studies have described outcomes and mortality predictors for patients post hematopoietic stem cell transplantation (HSCT), but fewer data exist regarding the category of non-HSCT patients. PROCEDURE: All oncohematologic non-HSCT patients ≤18 years requiring PICU admission from 1998 to 2015 in our tertiary-care academic hospital were retrospectively evaluated by means of the pediatric hematology-oncology unit database and the Italian PICUs data network database. We assessed the relation between demographic and clinical characteristics and 90-day mortality after PICU admission. RESULTS: Of 3750 hospitalized oncohematologic patients, 3238 were non-HSCT and 63 (2%) of them were admitted to the PICU. Patients were mainly affected by hematological malignancies (70%) and mostly were in the induction-therapy phase. The main reasons for admission were respiratory failure (40%), sepsis (25%), and seizures (16%). The median PICU stay was 5 days (range 1-107). The mortality rate at PICU discharge was 30%, and at 90 days it was 35%. Fifty-five percent of deaths happened in the first 2 days of the PICU stay. Cardiac arrest (P = .007), presence of disseminated intravascular coagulation (DIC, P = .007), and acute kidney injury (AKI) at PICU admission (P < .001) and during PICU stay (P = .021) were significant predictors of mortality in the multivariate analysis. Respiratory failure and mechanical ventilation were not associated with mortality. CONCLUSIONS: A relatively small percentage of non-HSCT patients required PICU admission, but the mortality rate was still high. Hemodynamic instability, DIC, and AKI, but not respiratory failure, were significant predictors of mortality.

The pathogen-reduced red blood cell suspension: single centre study of clinical safety and efficacy in children with oncological and haematological diseases.

BACKGROUND: Transmission of pathogens through blood transfusion is still of great concern to clinicians, patients and blood providers. Pathogen reduction technologies (PRT) have been successfully applied for the treatment of labile blood components, such as plasma, platelets and whole blood (WB), which are now used in routine in many countries. We report the clinical evaluation of suspension of red blood cells (RBC-S) derived from the WB treated with riboflavin and UV light (RF+UV). STUDY DESIGN AND METHODS: Seventy paediatric patients (0·3-17·1 years old) suffering from different malignant disorders were recruited and assigned to two groups: the control group (C) received transfusions of γ-irradiated RBC-S. The experimental group (T) received RBC-S derived from WB, treated with RF+UV. Clinical efficacy was evaluated during follow-up periods by Hb and Ht increments, and needs for transfusion support. Safety was assessed through active surveillance, recording post-transfusion reactions, anti-erythrocyte's antibody formation, haptoglobin and serum potassium levels. RESULTS: The clinical efficacy of RBC-S in both groups was similar: mean post-transfusion Hb concentration (101·6 ± 7·57 g/l vs. 100 ± 8·3 g/l; P = 0·43), and Ht level (28·5 ± 2·42% vs. 28·2 ± 2·7%; P = 0·66). Transfusion of pathogen-reduced RBC-S did not increase the frequency of transfusion reactions and did not induce an excessive immune response in the follow-up period. CONCLUSION: Transfusion of RBC-S, obtained from pathogen-reduced WB, is a promising method to increase the safety of blood component therapy for paediatric patients with malignant disorders without affecting clinical efficacy. A randomized clinical trial including more patients should follow this pilot study to confirm its results.

Association of systolic blood pressure drop with intravenous administration of itraconazole in children with hemato-oncologic disease.

PURPOSE: Although few adverse effects have been reported for itraconazole, a widely used antifungal therapy for febrile neutropenia, we found intravenous (IV) itraconazole to be associated with serious cases of blood pressure (BP) drop. We therefore evaluated the incidence and risk factors for BP drop during IV administration of the drug. MATERIALS AND METHODS: We reviewed the medical records of children with hemato-oncologic disease who were treated with IV itraconazole from January 2012 to December 2013. By analyzing systolic BP (SBP) measurements made from 4 hours before through to 4 hours after itraconazole administration, we evaluated the changes in SBP and the risk factors for an SBP drop, especially clinically meaningful (≥ 20%) drops. RESULTS: Itraconazole was administered 2,627 times to 180 patients. The SBP during the 4 hours following itraconazole administration was lower than during the 4 hours before administration (104 [53.0-160.33 mmHg] versus 105 [59.8-148.3 mmHg]; P<0.001). The decrease in SBP was associated with the application of continuous renal replacement therapy (CRRT) (P=0.012) and the use of inotropic (P=0.005) and hypotensive drugs (P=0.021). A clinically meaningful SBP drop was seen in 5.37% (141 out of 2,627) of the administrations, and the use of inotropics (odds ratio [OR] 6.70, 95% confidence interval [CI] 3.22-13.92; P<0.001), reducing the dose of inotropics (OR 8.08; 95% CI 1.39-46.94; P=0.02), CRRT (OR 3.10, 95% CI 1.41-6.81; P=0.005), and bacteremia (OR 2.70, 95% CI 1.32-5.51; P=0.007) were risk factors, while age was a protective factor (OR 0.93, 95% CI 0.89-0.97; P<0.001). CONCLUSION: A decrease in SBP was associated with IV administration of itraconazole. It was particularly significant in younger patients with bacteremia using inotropic agents and during application of CRRT. Careful attention to hypotension is warranted during IV administration of itraconazole in this group of patients.

Utilidad del PET--FDG en patología gineco-oncológica / Usefulness of PET--FDG in gynecological-oncological pathology

El PET-FDG es un estudio de imágenes de cuerpo entero que evalúa el metabolismo glucídico celular. Su mayor utilidad es en oncología tanto en adultos como en niños. Permite distinguir tumores malignos de benignos, seleccionar los sitios de biopsia, etapificar las neoplasias, determinar la respuesta al tratamiento y distinguir entre cicatriz y enfermedad residual post tratamiento. Diversos estudios han concluido que el PET-FDG es un examen útil en el manejo de la patología gineco-oncológica, destacando en cáncer de endometrio, cérvico uterino y ovárico. En este trabajo, se revisan las indicaciones de la técnica en las diversas patologías ginecológicas neoplásicas y su rendimiento. Asimismo, se presenta la experiencia chilena inicial realizada en el Hospital Militar de Santiago con equipo PET dedicado, donde se han estudiado más de 1.500 pacientes en su gran mayoría oncológicos.

FDG-PET is a whole body scan that evaluates glucose cell metabolism. Its main utility is in adult and children oncology. PET scan is useful differentiating benign from malignant neoplasm, selecting the site for biopsy, staging of the malignancy, evaluating response to therapy and distinguishing scar from residual neoplasm. Different studies have concluded that FDG-PET is a useful study in the gyneco-oncological management, especially in endometrial, cervical and ovarian cancer. This work reviews the principal indications of PET in this pathology and also the initial Chilean experience at the Military Hospital of Santiago with a dedicated PET, where we have studied more than 1,500 cases, most of them in cancer patients.

La enfermedad oncológica como un proceso de pérdidas / Oncologic disease as a loss process

La enfermedad oncológica se inscribe en la vida del paciente como un continuo de pérdidas, que se inicia con la pérdida de salud y que puede llegar hasta la pérdida de la propia vida. El cómo el sujeto enfrenta en su vida adulta esta situación estará determinado por sus experiencias tempranas de apego y separación, vivenciando las pérdidas producidas por la enfermedad con mayor o menor intensidad. Es importante tener presente que un paciente oncológico es un sujeto, que desde el punto de vista psicológico es, altamente vulnerable, y se hace necesario mantener un rol psicoprofiláctico, que permita prevenir el desarrollo de trastornos psicológicos mayores y faciliten el proceso de adaptación al proceso de enfermedad oncológica.

An oncologic disease arrives to the patient's life as a continuos loss process that begins with the loss of health and may possibly end with the loss of the patient's life. How the patient faces this situation as an adult, will depend upon the attachment and separation experiences in the early years, thus experiencing the health resulting losses in a more or less intense way. It is worth keeping in mind that an oncologic patient is an individual who from a psychological perspective is highly vulnerable, which makes it necessary to play a psychoprophylactic role that allows us to prevent the development of major psychological disorders and facilitate the adaptation process to this oncologic disease.