Genetic Markers of Acute Childhood B-Lineage Lymphoblastic Leukemia in the Kazakh Population.

INTRODUCTION: To investigate the genetic contribution of 24 GWAS-associated polymorphic gene variants on the development of children's B-lineage acute lymphoblastic leukemia (B-ALL) in an ethnically homogeneous population of Kazakhs. METHODS: A study of 205 children with B-ALL and 204 healthy children was conducted. Genotyping of polymorphic loci was carried out using the TaqMan method. RESULTS: Significant associations (p < 0.05) with the risk of childhood B-ALL were found for twelve variants, including rs6457327 of the HLA gene, rs4251961 of the IL1RN gene, and rs1800630 of the TNF gene. Carriage of the minor allele A of the protective rs1801157 polymorphism A of the CXCL12 gene reduces the risk of B-ALL in the Kazakh population by 40%. DISCUSSION: The results reveal significant associations of polymorphic genetic variants, which can serve as a basis for the development of effective methods for predicting the risk of B-ALL, early diagnosis, and timely treatment.

Improving Drug Safety in Pediatric and Young Adult Patients with Hemato-Oncological Diseases: A Prospective Study of Active Pharmacovigilance.

The acquisition of relevant pediatric clinical safety data is essential to ensure tolerable drug therapies. Comparing the real number of Adverse Drug Reaction (ADR) reports in clinical practice with the literature, the idea of ADR underreporting emerges. An active pharmacovigilance observational prospective study was conducted to assess the safety of oncology pharmacological prescriptions in patients aged 0-24 years at Institute for Maternal and Child Health IRCCS Burlo Garofolo in Trieste and IRCCS CRO National Cancer Institute in Aviano (Italy) between January 2021 and October 2023. Prescriptions and ADRs were evaluated by a multidisciplinary team. A total of 1218 prescriptions for 38 patients were analyzed, and 190 ADRs of grade 3-5 were collected. As compared to historical data, we registered a significant increase (p < 0.001) in the number of ADRs. The risk of ADR was 3.4 times higher in the case of off-label prescriptions compared to on-label ones (OR 3.4; [1.47; 7.89]; p-value = 0.004). The risks of error and near-miss were reported for 6.3% and 18.2% of total prescriptions, respectively. Of the total of 133 interactions, 47 (35.3%) resulted in ADRs. This study shows the importance of pro-active pharmacovigilance to efficiently highlight ADRs, and the fundamental role of multidisciplinary teams (oncologist, pharmacist, pharmacologist, pediatrician, nurse) in improving patients' safety during therapy.

Making the Best in a Bad Job: A Psychoanalytic Perspective on Communication with Children and Adolescents with Severe Physical Condutions.

Ill children/adolescents who suffer from severe organic diseases have to cope with their inner experiences, therapies, and the global burden of the disease. Although sometimes depression, anger, and death anxiety are openly encountered in medical settings, other times they can be partially hidden by a reactive and defensive path. In these scenarios, psychoanalysis is challenged to contribute the best comprehension of the intimate communication, maybe hidden, and the needs of the ill patients to express themselves. The best way a child can talk about himself is through spontaneous creativity. The adult's task is to facilitate the creation of an empty space and to recognize the child's mode of communication. There may be intense emotional reactions that the adult has to tolerate to not move the patient towards an over-adaptation. These over-adaptations entail the child being forced to feel good or have fun, thereby causing them to escape from their inner experience. The loss of the child's reality forms an additional burden to the child. The most valid indicator of this attitude is the ability to not take counterphobic attitudes but to allow the depression to be shared in a contact space between the child's true self and the perceived environment.

Effects of exercise training on cancer patients undergoing neoadjuvant treatment: A systematic review.

OBJECTIVES: This systematic review aimed to analyze the effects of different exercise protocols on physical fitness (cardiorespiratory fitness, muscle strength, and body composition), quality of life, cancer-related fatigue, and sleep quality in patients with different types of cancer undergoing neoadjuvant treatment. DESIGN: Systematic review. METHOD: A comprehensive search of existing literature was carried out using four electronic databases: PubMed, Scopus, Web of Science, and Cochrane Library (published until October 19, 2022). All databases were searched for randomized controlled trials, quasi-experimental investigations, and pre-post investigations assessing the effects of exercise in cancer patients during neoadjuvant treatment. Excluded articles included multicomponent interventions, such as exercise plus diet or behavioral therapy, and investigations performed during adjuvant treatment or survivorship. The methodological quality of each study was assessed using the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Twenty-seven trials involving 999 cancer patients were included in this review. The interventions were conducted in cancer patients undergoing neoadjuvant treatment for rectal (n = 11), breast (n = 5), pancreatic (n = 4), esophageal (n = 3), gastro-esophageal (n = 2), and prostate (n = 1) cancers, and leukemia (n = 1). Among the investigations included, 14 utilized combined exercise protocols, 11 utilized aerobic exercise, and two utilized both aerobic and resistance training separately. Exercise interventions appeared to improve cardiorespiratory fitness, muscle strength, body composition, and quality of life, although many investigations lacked a between-group analysis. CONCLUSION: Despite limited evidence, exercise interventions applied during neoadjuvant treatment demonstrate promising potential in enhancing cardiorespiratory fitness, muscle strength, body composition, and overall quality of life. However, a scarcity of evidence remains on the effects of exercise on cancer-related fatigue and sleep quality. Further research with high-quality randomized controlled trials is warranted.

Promoção do conforto da pessoa com cancro de cabeça e pescoço em fim de vida e família: intervenção de enfermagem / Promoting comfort for people with head and neck cancer at the end of life and their families: nursing intervention

O presente relatório foi desenvolvido no âmbito da unidade curricular de estágio com relatório do 3º semestre do 12º Curso de Mestrado/Especialidade em Enfermagem Médico-Cirúrgica na vertente de Enfermagem Oncológica. Exercendo funções num Serviço de Otorrinolaringologia e, contatando diariamente com pessoas com CCP, verifico, após reflexão pessoal, que esta população sofre um enorme impacto no seu conforto, em particular, no fim de vida, sendo uma perceção igualmente partilhada pelos colegas do serviço. Além disso, a equipa de enfermagem refere sentir dificuldades na prestação de cuidados promotores do conforto, nomeadamente, no controlo de sintomas do foro físico, psicológico, social e espiritual a esta população e sua família. Deste modo, com a elaboração deste relatório, pretendo demonstrar o processo de desenvolvimento de competências de enfermeiro especialista na intervenção de enfermagem à pessoa com CCP em fim de vida e sua família, contribuir para a melhoria da qualidade dos cuidados prestados e promover o seuconforto. Sustentada na metodologia de projeto, realizei três estágios onde, nos dois primeiros, potenciou-se um processo de desenvolvimento de competências técnicas, relacionais e pessoais para o cuidar da pessoa em fim de vida. No último estágio, apliquei o que foi desenvolvido em termos de competências de enfermeiro especialista bem como capacitei a equipa de enfermagem através da realização de duas formações onde foram apresentadas as intervenções de enfermagem promotoras do conforto à pessoa com CCP em fim de vida e família, conteúdos acedidos através da revisão da literatura e observação da prática de cuidados. Foram ainda elaborados e apresentados um guia orientador de cuidados dirigido aos enfermeiros do Serviço de ORL que será uma ferramenta chave para a prática bem como um protocolo de articulação com a EIHSCP que permitirá estruturar a resposta às necessidades de cuidados paliativos da pessoa com CCP através da parceria entre as equipas de enfermagem dos Serviços ORL ­ internamento e da EIHSCP, sendo que ambos irãopotenciar uma resposta mais precoce e de qualidade pela equipa de enfermagem e contribuir para a promoção do conforto da pessoa em fim de vida e família.

This report was developed within the internship curricular unit with report of the 3rd semester of the 12th Course of Master/Specialty in Medical-Surgical Nursing in the Oncological Nursing field. Performing functions in an Otorhinolaryngologist Service and contacting daily with CCP patients, I verified after a personal reflection, that this population suffers an enormous impact in its comfort, particularly, in the end of life. This perception is equally shared by the co-workers. Furthermore, the nursing team refers to have difficulties in the provision of care that maximize comfort, namely the control of symptoms of the physical, psychological, social and spiritual forum to this population and its family. This way, with the elaboration of this report, I intend to demonstrate the development process of skills of a specialist nurse in the nursing intervention to the person with CCP in end of life and its family, contributing to the improvement of the quality of the provided care and promotion of their comfort. Supported by the project methodology, three internships were made where, in the first two, it was strengthened a development process of technical, relationship and personal skills to the care of a person in end of life. In the last internship, I applied what was developed in terms of skills of specialist nurse as well as I enabled the nursing team through two trainings where it was disclosed the nursing interventions promoters of comfort to the person with CCP in end of life and family, contents assessed through the literature review and observation of practical cares. It was also made and presented a guiding guide of cares addressed to the nurses of the ORL Service which will be a key tool for the practicing as well as an articulation protocol with the EIHSCP, which will allow to organize the answer to the needs of palliative care of the person with CCP through the partnership between the nursing teams of the ORL Services ­ internment and the EIHSCP, both of which will potentiate an earlier and with more quality action by the nursing team as well as promote the comfort of the person in end of life and its family.

Prevention and treatment of cancer associated venous thromboembolism - interdisciplinary consensus.

The increasing volume of the data and experience with direct oral anticoagulants (DOACS) in the primary and secondary prevention of venous thromboembolism in oncologic patients (CAVTE) has recently lead to changes in several international guidelines. We reflect these changes within the conditions in Slovak republic. In the primary prevention of CAVTE we recognise oncosurgical patients and nonsurgical patients: hospitalised and out patients. Low molecular weight heparins are still dominant in the primary prevention of CAVTE. Regarding the treatment and the secondary prevention of CAVTE, we recommend always to consider the possibility to use DOACs as they proved to be non inferior to LMWH. However, LMWH should be prefered over DOACs as well as over warfarin (VKA) in all patients who are in a clinically unstable condition with the high risk of bleeding and/or interaction with the systemic treatment. Primarily in the patients with intraluminal tumours of the upper part of the gastrointestinal tract and genitourinary tumours with the high risk of bleeding. As for the lack of data, LMWH are still preferd also in patients with primary tumours and metastatic disease of the central nervous system and in hemato oncology.

Hemato-Oncological Diseases as Risk Factor for Recurrence or Metastasis of Pleomorphic Dermal Sarcoma.

Background: Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are increasingly common sarcomas of the skin with a genetic UV signature. Immunosuppression is a known risk factor for developing other UV-induced skin cancers such as cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and Merkel cell carcinoma with increased mortality. In case reports or small case series of AFX/PDS patients, immunosuppression has been hypothesized as a risk factor for the development of distant metastases. The aim of the present study was to analyze immunosuppression as a risk factor for AFX/PDS in a large patient cohort. Methods: A cohort of 164 patients with AFX/PDS (47 AFX and 117 PDS) was collected between 2003 and 2021 and analyzed for clinicopathological data with a special focus on immunosuppression. Results: Of all patients, 29.9% had any kind of immunosuppression; 6.4% of the AFX and 12.0% of the PDS patients had underlying hemato-oncological diseases. Patients with immunosuppression due to an underlying hemato-oncological disease had a significantly increased risk of progressing to (p = 0.010) and developing distant organ metastases (p = 0.000). Conclusions: Immunosuppression seems to be a risk factor for developing AFX/PDS with worse clinical outcomes. Therefore, immunosuppression, especially underlying hemato-oncological diseases, should be considered in the treatment and follow-up care of patients with AFX/PDS.

Psoriatic patients with a history of cancer: A real-life experience with Apremilast treatment for 104 weeks.

Psoriasis is a multifactorial, chronic, auto- inflammatory disease, with a worldwide prevalence of around 2%, subtended by robust genetic predisposition and autoimmune pathogenic traits. The disease, mainly involving the skin and joints, is featured by erythemato-squamous lesions, with a chronic relapsing course and relevant systemic comorbidities. Apremilast is a novel oral agent that has recently been made available to dermatologists for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Although it is considered as relatively safe molecule with few contraindications, experience with Apremilast in the real-world setting for cancer patients with moderate-to-severe plaque psoriasis is lacking. Hence, we report the real-life experience in patients with psoriasis and a history of cancer who underwent treatment with Apremilast for 104 weeks.

Glomerular filtration rate in children and young adults with haemato-oncological disease and infection is best described by three-compartment iohexol model.

BACKGROUND: Children with cancer and infection may develop glomerular hyperfiltration. With the aim to determine the prevalence of glomerular hyperfiltration in children and young adults with haemato-oncological disease and infection, we developed population pharmacokinetic model of iohexol. We further aimed to assess the accuracy of estimated glomerular filtration rate (eGFR) equations and single- or two-point measured GFR (mGFR) formulas compared with GFR based on iohexol clearance from our population pharmacokinetic model (iGFR). PROCEDURE: Hospitalised patients (0.5-25 years) with haemato-oncological disease and infection were included if their eGFR was ≥80 ml/min/1.73 m2 at the screening visit. Iohexol plasma concentrations were described by population pharmacokinetic model. Bias, precision and accuracy of 23 eGFR equations and 18 mGFR formulas were calculated. RESULTS: Total of 32 iohexol administrations were performed in 28 patients. Median (range) eGFR was 136 ml/min/1.73 m2 (74-234) and age 15.1 years (0.8-26.0). Three-compartment model with allometric scaling of central, one peripheral compartment and clearance (with power 0.75) to weight fitted the best. Median (range) iGFR was 103 ml/min/1.73 m2 (68-140). All except one eGFR equation overestimated GFR. Lund-Malmö revised eGFR equation performed the best, followed by Gao equation. Of single- or two-point mGFR formulas, 15 overestimated iGFR. Modified Jacobsson formula at 5.5 hours performed the best, followed by Fleming formula at 3 hours. CONCLUSIONS: In children and young adults with haemato-oncological disease and infection, renal function is best described by iohexol clearance from three-compartment pharmacokinetic model, while eGFR equations and single- and two-point mGFR formulas overestimate iGFR.

Comunicación de la verdad en oncología desde la visión de la bioética médica / Communication of the truth in oncology from the perspective of medical bioethics

RESUMEN Introducción: La relación médico paciente en oncología se basa en el respeto por la vida, unido de forma constante en la aceptación de la vulnerabilidad y al reconocimiento de la inevitabilidad de la muerte. La comunicación de la verdad, particularmente cuando se trata de informar malas noticias, es una situación estresante, difícil y que demanda la adecuada preparación del personal de la salud. Objetivo: Comentar sobre los fundamentos de la comunicación de la verdad en las enfermedades oncológicas y los puntos relevantes en la relación médico paciente. Desarrollo: Comunicar la verdad entraña varios dilemas éticos en oncología y a veces la información se maneja incorrectamente por el equipo médico. El consenso es no mentir, sin normas rígidas, "ocultar la verdad" y la "conspiración del silencio"; no son del todo errados, el profesional de la salud debe respetar el derecho del paciente de estar informado y a su autonomía, lo que facilitará la toma de decisiones. La relación médico paciente ya cede el terreno a formas más personalistas de relación y el respeto a la libertad individual. Conclusiones: Los fundamentos de la comunicación de la verdad en la enfermedad oncológica, se basan en los principios de la ética y bioética médica, la verdad garantiza una comunicación transparente y enriquecedora. Los puntos relevantes de la RMP consisten en lograr la adecuada alianza terapéutica entre el médico y paciente, en la mejora de su calidad de vida.

ABSTRACT Introduction: The doctor-patient relationship in oncology is based on respect for life, constantly linked to the acceptance of vulnerability and the recognition of the inevitability of death. The communication of the truth, particularly when it comes to reporting bad news, is a stressful and difficult situation that requires the proper preparation of health personnel. Objective: To comment the fundamentals of the communication of the truth in oncological diseases and the relevant points in the doctor-patient relationship. Development: Communicating the truth involves several ethical dilemmas in oncology and sometimes the medical team handles the information incorrectly. The consensus is not to lie, without rigid rules, "hide the truth" and the "conspiracy of silence"; are not entirely wrong, the health professional must respect the patient's right to be informed and their autonomy, which will facilitate decision-making. The doctor-patient relationship is already giving way to more personal forms of relationship and respect for individual freedom. Conclusions: The fundamentals of the communication of the truth in oncological disease are based on the principles of medical ethics and bioethics, the truth guarantees a transparent and enriching communication. The relevant points of the doctor patient relationship consist of achieving the adequate therapeutic alliance between the doctor and the patient, in order to improve their quality of life.

SeekFusion - A Clinically Validated Fusion Transcript Detection Pipeline for PCR-Based Next-Generation Sequencing of RNA.

Detecting gene fusions involving driver oncogenes is pivotal in clinical diagnosis and treatment of cancer patients. Recent developments in next-generation sequencing (NGS) technologies have enabled improved assays for bioinformatics-based gene fusions detection. In clinical applications, where a small number of fusions are clinically actionable, targeted polymerase chain reaction (PCR)-based NGS chemistries, such as the QIAseq RNAscan assay, aim to improve accuracy compared to standard RNA sequencing. Existing informatics methods for gene fusion detection in NGS-based RNA sequencing assays traditionally use a transcriptome-based spliced alignment approach or a de-novo assembly approach. Transcriptome-based spliced alignment methods face challenges with short read mapping yielding low quality alignments. De-novo assembly-based methods yield longer contigs from short reads that can be more sensitive for genomic rearrangements, but face performance and scalability challenges. Consequently, there exists a need for a method to efficiently and accurately detect fusions in targeted PCR-based NGS chemistries. We describe SeekFusion, a highly accurate and computationally efficient pipeline enabling identification of gene fusions from PCR-based NGS chemistries. Utilizing biological samples processed with the QIAseq RNAscan assay and in-silico simulated data we demonstrate that SeekFusion gene fusion detection accuracy outperforms popular existing methods such as STAR-Fusion, TOPHAT-Fusion and JAFFA-hybrid. We also present results from 4,484 patient samples tested for neurological tumors and sarcoma, encompassing details on some novel fusions identified.

Machine Learning for Early Warning of Septic Shock in Children With Hematological Malignancies Accompanied by Fever or Neutropenia: A Single Center Retrospective Study.

OBJECTIVES: The purpose of this article was to establish and validate clinically applicable septic shock early warning model (SSEW model) that can identify septic shock in hospitalized children with onco-hematological malignancies accompanied with fever or neutropenia. METHODS: Data from EMRs were collected from hospitalized pediatric patients with hematological and oncological disease at Shanghai Children's Medical Center. Medical records of patients (>30 days and <19 years old) with fever (≥38°C) or absolute neutrophil count (ANC) below 1.0 × 109/L hospitalized with hematological or oncological disease between January 1, 2017 and August 1, 2019 were considered. Patients in whom septic shock was diagnosed during the observation period formed the septic shock group, whereas non-septic-shock group was the control group. In the septic shock group, the time points at 4, 8, 12, and 24 hours prior to septic shock were taken as observation points, and corresponding observation points were obtained in the control group after matching. We employed machine learning artificial intelligence (AI) to filter features and used XGBoost algorithm to build SSEW model. Area under the ROC curve (AU-ROC) was used to compare the effectiveness among the SSEW Model, logistic regression model, and pediatric sequential organ failure score (pSOFA) for early warning of septic shock. MAIN RESULTS: A total of 64 observation periods in the septic shock group and 2191 in the control group were included. AU-ROC of the SSEW model had higher predictive value for septic shock compared with the pSOFA score (0.93 vs. 0.76, Z = -2.73, P = 0.006). Further analysis showed that the AU-ROC of the SSEW model was superior to the pSOFA score at the observation points 4, 8, 12, and 24 h before septic shock. At the 24 h observation point, the SSEW model incorporated 14 module root features and 23 derived features. CONCLUSION: The SSEW model for hematological or oncological pediatric patients could help clinicians to predict the risk of septic shock in patients with fever or neutropenia 24 h in advance. Further prospective studies on clinical application scenarios are needed to determine the clinical utility of this AI model.

First exercise group for Turkish breast cancer patients in Vienna - a pilot project to include Turkish migrants.

Background: The aim of this pilot study was to describe the acceptance and feasibility of an exercise intervention in breast cancer patients of Turkish origin in Austria by using a hand-held swinging-ring system.Methods: The inclusion period lasted 1 year (1 February 2016-31 January 2017). In a multicentre cooperation, Turkish female breast cancer patients were included by using face-to-face information, email, facebook®, phone, and notice boards. The exercise program consisted of 1) supervised and 2) home-based exercise by using the smovey® vibroswing system. Feasibility and acceptance were assessed by using the Austrian school grading system and a qualitative approach after 3 months. Furthermore, the six-minute walk test (6MWT), handgrip strength, body composition (BIA), and health-related quality of life (QOL) were assessed at baseline (T0) and after 3 months (T1).Results: Only 5 breast cancer patients could be included, from whom one dropped out due to breast cancer recurrence. The exercise intervention showed no side effects and was well accepted by all 4 patients. Furthermore, results of the 6MWT, handgrip strength, BIA, and QOL improved.Conclusion: These results indicate notable barriers towards regular physical activity in female Turkish breast cancer patients in Austria. Four out of five of those involved were comfortable with the intervention. Therefore, it seems to be essential to further address these barriers in order to plan and implement effective interventions.Implications for RehabilitationExercise is an effective means of improving health and quality of life experienced by female patients suffering from breast cancer.Although extensive efforts were taken only a minority of Turkish female patients attended a structured exercise program.It seems to be essential to further address barriers to exercise in order to plan and implement effective interventions.

Características y tratamiento del paciente oncológico en el marco de la actual pandemia de la COVID-19 / Characteristics and treatment of the oncologic patient in the midst of the current COVID-19 pandemic

Introducción: El cáncer constituye una de las principales causas de morbimortalidad en todo el mundo. Múltiples reportes indican lo peligroso que puede llegar a ser la COVID-19 en pacientes oncológicos. Objetivo: Caracterizar al paciente oncológico y su tratamiento en el marco de la actual pandemia de COVID-19. Material y Métodos: Se realizó una revisión bibliográfica para la cual se usaron 37 referencias bibliográficas en inglés y español para la cual se utilizó Pubmed/Medline, ScIELO, Scopus, ScienceDirect, así como fuentes oficiales como OMS y CDC. Desarrollo: Los pacientes oncológicos presentan un sistema inmune comprometido. La polipnea se presentó más en pacientes con cáncer con diagnostico de la COVID-19 que en aquellos sin antecedentes oncológicos. No se hallaron diferencias en relación con otros síntomas; sin embargo se detectaron lesiones de mayor severidad en la Tomografía Axial Computarizada. En estos pacientes deben reforzarse medidas preventivas y se plantea la posibilidad de retrasar los tratamientos quimioterapéutico y quirúrgico mientras sea posible, aunque debe tenerse en cuenta el riesgo que esto constituye. Todos los pacientes con cáncer deben clasificarse como de alto riesgo y los que contraigan el SARS-CoV-2, recibirán el mismo tratamiento que los pacientes no oncológicos. Conclusiones: Los pacientes oncológicos tienen un mayor riesgo que la población general de padecer formas graves de la COVID-19; de ahí que sea importante adoptar medidas preventivas adecuadas que no se opongan a la aplicación de un tratamiento oncológicamente adecuado; por tanto se hace necesario adaptar los esquemas previamente establecidos a la situación que vive el mundo actualmente(AU)

Introduction: Cancer is one of the main causes of morbidity and mortality around the world. Numerous reports indicate how dangerous COVID-19 can be for oncologic patients. Objective: To characterize the oncologic patient and the treatment to follow in the midst of the COVID-19 pandemic. Material and Methods: A bibliographic review, which included 37 bibliographic references in Spanish and English languages, was carried out. Pubmed/Medline, SciELO, Scopus, and ScienceDirect databases as well as other official sources such as WHO and CDC were used for the search. Development: Oncologic patients have a compromised immune system. Polypnea was more common in oncologic patients with COVID-19 than in patients without cancer. There were no differences in relation to other symptoms; however, more severe lesions were found in CT-Scans. In oncologic patients, preventive measures must be reinforced and both chemotherapeutic and surgical treatment should be delayed as long as possible; however, the risk must be considered. All patients with cancer must be classified as high risk patients and those infected with SARS-CoV-2 will receive the same treatment than non-oncologic patients. Conclusions: Oncologic patients have a higher risk of suffering from severe forms of COVID-19 than the general population; therefore, it is very important to take preventive measures that are not opposed to the administration of an adequate oncological treatment. Because of that, it is necessary to adapt the previously established protocols to the current situation the world is living(AU)

Mieloma múltiple asociado con hiperbetaglobulinemia en paciente cirrótico. Reporte de caso / Multiple Myeloma Associated with Hyperbetaglobulinemia in a Cirrhotic Patient. Case Report / Mieloma múltiplo associado a hiperbetaglobulinemia em paciente cirrótico. Reporte de caso

Resumen Introducción: El mieloma múltiple es una enfermedad hematooncológica de origen clonal, caracterizada por la producción anormal de células plasmáticas que producen un reemplazo progresivo de otras líneas hematopoyéticas. El 95 % de los casos condiciona el aumento de la producción de inmunoglobu-linas defectuosas, predominantemente IgG e IgA, detectadas en suero con pico monoclonal, definido por un deterioro progresivo de la función renal aguda, anemia, citopenias, dolor óseo agudo o crónico, fracturas patológicas, trastornos endocrinos recientes y, como en el caso de estudio, asociado con cirrosis hepática. Presentación del caso: Paciente masculino de 49 años, con cefalea, dolor abdominal, torácico, evacuaciones melénicas, disnea y signos de ascitis, con un tiempo de enfermedad de tres meses, con historia de dolor lumbosacro de tres años antes de su ingreso. Los exámenes auxiliares mostraron pancitopenia, perfil de coagulación alterado, función renal alterada, inversión de albúmina-globulina, hiperuricemia, ascitis, lesiones óseas líticas, hipergammapatía monoclonal de tipo IgA relacionado con hiperbetaglobulinemia. Los exámenes específicos dieron como diagnóstico mieloma múltiple IgA EC IIIB más cirrosis hepática. Se presenta este caso como inusual por elevación de proteínas en suero, tanto beta como gamma, producto de dos patologías concomitantes. Conclusión: paciente con dos enfermedades simultáneas, en ambos casos con elevación de globulinas, lo que podría confundir el diagnóstico; el estado de inmunosupresión mejora con la administración de inmunoglobulinas y de tratamiento para la enfermedad base.

Abstract Introduction: The multiple myeloma is a hemato-oncological disease of clonal origin, characterized by the abnormal production of plasma cells that produce a progressive replacement of the other hema-topoietic lines in the bone marrow. In 95 % of the cases, the condition showed an increase in the production of defective immunoglobulins, predominantly IgG and IgA detected in serum with monoclonal peak, characterized by progressive deterioration of acute renal function, anemia, cytopenias, acute or chronic bone pain, pathological fractures, and recent endocrine disorders. The present case associated with hepatic cirrhosis. Case presentation: A 49-year-old male patient with headache, abdominal pain, thoracic, manes, dyspnea and signs of ascites with a 3-month disease time, and lumbosacral pain history of 3 years before admission. Auxiliary examinations showed pancytopenia, altered coagulation profile, impaired renal function, albumin-globulin inversion, hyperuricemia, ascites, lytic bone lesions, and monoclonal hypergammapathy of IgA type associated with hyperbetaglobulinemia. The specific exams gave as diagnosis multiple IgA EC IIIB myeloma, plus liver cirrhosis, this case is presented as unusual by elevation of serum proteins in both beta and gamma product of two concomitant pathologies. Conclusion: A patient with two simultaneous diseases, both cases with globulin elevation that could confuse the diagnosis, whos state of immunosuppression improved with the administration of immunoglobulins and the treatment for the base disease.

Resumo Introdução: O mieloma múltiplo é um doença hemato-oncológica de origem clonal, caracterizada pela produção anormal de células plasmáticas que produzem uma substituição progressiva de outras linhas hematopoiéticas. O 95 % dos casos, condiciona o aumento da produção de imunoglobulinas defeituosas, predominantemente IgG e IgA detectadas em soro com pico monoclonal, caracterizada por um deterioro progressivo da função renal aguda, anemia, citopenias, dor óssea aguda ou crónica, fraturas patológicas, transtornos endócrinos recentes e no presente caso associado à cirrose hepática. Apresentação do caso: Paciente masculino de 49 anos com cefaleia, dor abdominal, torácica, melena, dispneia e signos de ascite com um tempo de doença de 3 meses, com história de dor lombossacral 3 anos antes de seu ingresso, os exames auxiliares mostraram pancitopenia, perfil de coagulação alterada, função renal alterada, investimento de albumina-globulina, hiperuricemia, ascite, lesões ósseas líticas, hipergamapatia monoclonal de tipo IgA associado a hiperbetaglobulinemia. Os exames específicos deram como diagnóstico mieloma múltiplo IgA EC IIIB mais cirrose hepática, se apresenta este caso como inusitada por elevação de proteínas em soro tanto beta quanto gama produto de duas patologias concomitantes. Conclusões: Paciente com duas doenças simultâneas em ambos os casos com elevação de globulinas que poderiam confundir o diagnóstico e pelo estado de imunossupressão melhora com a administração de imunoglobulinas e tratamento para a doença base.

13N-NH3 PET/CT in oncological disease.

13N-Ammonia (13N-NH3) is widely used positron emission tomography/computed tomography (PET/CT) radiotracer for the measurement of myocardial blood perfusion; the possible role of 13N-NH3 PET or PET/CT in oncological disease is not yet clear. Aim of this review is to evaluate the diagnostic performances of 13N-NH3 PET in this field. A comprehensive computer literature search of the PubMed/MEDLINE, Scopus, and Embase databases was conducted including articles up to June 2019. Eighteen articles were finally included in the review. From the analyses of the selected studies, the following main findings could be drawn: (1) 13N-NH3 PET is useful in discriminating between gliomas and non-neoplastic brain lesions, and among gliomas between high-grade and low-grade gliomas; (2) 13N-NH3 PET have better diagnostic performance than 18F-FDG in studying gliomas; (3) a combination of 13N-NH3 PET and 18F-FDG PET may be useful to differentiate between several cerebral lesions (gliomas, cerebral lymphoma, meningioma); (4) only preliminary results about the positive impact in liver and prostate cancer.

Assessing drug response in engineered brain microenvironments.

Tissue engineered systems are important models for the testing and discovery of therapeutics against a number of diseases. The use of these models in vitro can expand both our understanding of the mechanisms behind disease and allow for higher throughput and personalized modeling of therapeutic response. Over the past decade there has been an explosion of models of neurological disorders that can be used in vitro to study new therapies against devastating neurodegenerative, neurodevelopmental, and neuro-oncological disease. These models span several types of engineered microenvironments which are produced using microfluidic devices, microtissue technology and/or the incorporation of biomaterial scaffolds to model neurological conditions such as; Alzheimer's disease, idiopathic autism, Parkinson's disease, Zika-induced microcephaly and neoplasms. Using engineered brain microenvironments, therapeutics can be tested in more physiologically relevant ways leading to new knowledge of the underlying causes and interactions occurring at the tissue level. However, much is still left to learn and model within these systems to make them truly valuable in the discovery and testing of novel therapies. Here we review the current state of the art of engineered brain microenvironments being used specifically to screen and test new therapeutic strategies and discuss the current benefits and limitations that still exist.

Rebound thymic hyperplasia after bone marrow transplantation in children with haemato-oncological diseases.

AIM OF THE STUDY: To evaluate prevalence of rebound thymic hyperplasia (RTH) after bone marrow transplantation (BMT) in paediatric patients with haemato-oncological diseases. MATERIAL AND METHODS: Between February 2013 and December 2017, BMT was performed in 189 paediatric patients with haemato-oncological diseases in our institution. Fifty-six patients who underwent at least two chest computed tomography (CT) exams performed before and after BMT were included in the study. Maximum transverse and anterior-posterior (AP) diameters and CT attenuation of the thymus were measured on axial images. Thymic enlargement was considered when both transverse and AP diameters increased. RTH was defined as the presence of thymic enlargement on CT after BMT relative to the CT taken before. RESULTS: Twenty of 56 patients (36%) demonstrated RTH (12 boys, 8 girls; age range = 4-18 years; median age = 9.8 years). In 20 patients with RTH, seven patients (35%) were diagnosed with ALL, five patients (25%) with thalassemia, two patients (10%) with AML, and one patient (5%) with various diseases. Mean follow-up period between pre-BMT CT and BMT was 46 days, which was 239 days between BMT and post-BMT CT. Mean thymic transverse and AP diameters were 9 mm and 16 mm, respectively, before BMT, which were 17 mm and 33 mm after BMT. Mean HU was 57 on contrast enhanced and 35 on unenhanced images before BMT, which were 59 and 36, respectively, after BMT. CONCLUSIONS: RTH is common finding after BMT in children with various haemato-oncological diseases and should be taken under consideration in paediatric patients after BMT.

Differential Diagnosis: Retroperitoneal Fibrosis and Oncological Diseases.

Retroperitoneal fibrosis is a connective disease of the auto-inflammatory/auto-immune type of the retroperitoneum with unknown etiology and pathological mechanism. The manifestations of the pathology can be local or systemic. Amongst the local symptoms, the dull and constant pain in the hips, back or abdomen is the most frequent. We report here a case of a 47-year-old woman, whose pathogenic mechanism could be related to an "IgG4-related disease" disorder as suggested by an increased serum level of this subclass of IgG and the positive immunohistochemistry. The diagnosis is not easy, because this pathology generates masses; adenomegalies with retro peritoneal development, that makes it similar to lymphomas or metastases from ovarian tumors.