High False-Positive Rate of (1,3)-ß-D-Glucan in Onco-Hematological Patients Receiving Immunoglobulins and Therapeutic Antibodies.

Immunoglobulins and/or therapeutic antibody preparations are associated with a high rate of false-positive (1,3)-ß-D-glucan (BDG) tests in onco-hematological patients routinely screened for fungal infections. The benefit of BDG monitoring shall be balanced against the risk of false-positive tests leading to unnecessary investigations and costs in this population.

Clinical, economic and organizational impact of pharmacist interventions on injectable antineoplastic prescriptions: a prospective observational study.

BACKGROUND: Pharmacists play a key role in ensuring the safe use of injectable antineoplastics, which are considered as high-alert medications. Pharmaceutical analysis of injectable antineoplastic prescriptions aims to detect and prevent drug related problems by proposing pharmacist interventions (PI). The impact of this activity for patients, healthcare facilities and other health professionals is not completely known. This study aimed at describing the clinical, economic, and organizational impacts of PIs performed by pharmacists in a chemotherapy preparation unit. METHODS: A prospective 10-week study was conducted on PIs involving injectable antineoplastic prescriptions. Each PI was assessed by one of the four multidisciplinary expert committees using a multidimensional tool with three independent dimensions: clinical, economic and organizational. An ancillary quantitative evaluation of drug cost savings was conducted. RESULTS: Overall, 185 patients were included (mean age: 63.5 ± 13.7 years; 54.1% were male) and 237 PIs concerning 10.1% prescriptions were recorded. Twenty one PIs (8.9%) had major clinical impact (ie: prevented hospitalization or permanent disability), 49 PIs (20.7%) had moderate clinical impact (ie: prevented harm that would have required further monitoring/treatment), 62 PIs (26.2%) had minor clinical impact, 95 PIs (40.0%) had no clinical impact, and 9 PIs (3.8%) had a negative clinical impact. For one PI (0.4%) the clinical impact was not determined due to insufficient information. Regarding organizational impact, 67.5% PIs had a positive impact on patient management from the healthcare providers' perspective. A positive economic impact was observed for 105 PIs (44.3%), leading to a saving in direct drug costs of 15,096 €; 38 PIs (16.0%) had a negative economic impact, increasing the direct drug cost by 11,878 €. Overall cost saving was 3218€. CONCLUSIONS: PIs are associated with positive clinical, economic and organizational impacts. This study confirms the benefit of pharmacist analysis of injectable antineoplastic prescriptions for patient safety with an overall benefit to the healthcare system.

Exercise prescription and tailored physical activity intervention in onco-hematology inpatients, a personalized bedside approach to improve clinical best practice.

Therapy of hematological malignancies lasts for long periods implicating various complications. The chemotherapy induces fatigue and forces bed rest. These features strongly contribute to a general impairment of the physical efficiency. Oppositely, an increase of physical exercise can prevent or reduce this weakening. Few trials examined the efficacy of an exercise in onco-hematological inpatients, during their hospitalization. Therefore, this study aimed to determine the feasibility of an inter-hospital intervention and the beneficial role of a tailored exercise program in the maintenance of the physical function in onco-hematological inpatients. The study included 42 patients, which were allocated in two groups. In the intervention group (IG) a tailored exercise protocol during patient's hospitalization was administered. Exercise protocol was focused on development of strength, balance control, and flexibility; sessions were directly performed in the patient's hospital room everyday for 15 to 30 minutes. Exercise was supervised by an exercise specialist and driven by a multimedia support. Control group (CG) remained physically inactive for all period of hospitalization. To examine the interaction between the two situations (T0 and T1 ) and the two groups (IG and CG) for all dependent variables, a 2 × 2 within-subjects contrasts model analysis of variance was applied. Within groups analysis displayed significant differences in grip and leg strength and in static balance control (P < 0.05) with medium to very large effect size. Results from this investigation showed that a tailored exercise protocol administered to hospitalized onco-hematological patients was feasible and efficient to promote the maintenance of their physical function, improving clinical best practice including exercise to the traditional treatment. Moreover, the magnitude of the difference between the IG and the CG underlined the importance to invite and stimulate patients to workout to preserve the physical function, counteracting side effects of chemotherapy treatments with a concurrent reduction in bed rest syndrome.

Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: Impact of national programme of antifungal prophylaxis.

The objective of the study was the analysis of incidence and outcome of invasive fungal disease (IFD) in children treated for malignancy (PHO, paediatric hematology-oncology) or undergoing hematopoietic cell transplantation (HCT) over a period of six consecutive years in nationwide study. A total number of 5628 patients with newly diagnosed malignancies and 971 patients after HCT (741 allo-HCT and 230 auto-HCT) were screened for infectious complications in biennial reports. IFD incidence was lower among PHO patients: 8.8% vs 21.2% (P < .0001) and survival from IFD was better: 94.2% vs 84.1% (P < .0001). Auto-HCT patients had lower incidence (10.9% vs 24.4%) and lower mortality than allo-HCT patients. Introduction of national antifungal prophylaxis programme in HCT and acute leukaemia patients decreased incidence of IFD in HCT (from 23.1% to 13.4%) and AML on conventional chemotherapy (from 36% to 23%) but not in ALL patients during chemotherapy. In multivariate analysis, the incidence of IFD was higher in patients after HCT, diagnosed for ALL, AML or NHL, and in patients > 10 years old. Factors contributing to death with infection were as follows: undergoing HCT, diagnosis of acute leukaemia (ALL or AML) and duration of treatment of infection > 21 days. In conclusion, the incidence of IFD in allo-HCT and in AML patients on chemotherapy has decreased after introduction of national programme of antifungal prophylaxis, while the incidence of IFD in ALL patients on chemotherapy did not change significantly. The outcome of IFD both in PHO and HCT patients has largely improved in comparison with historical international data.

[Continuous theoretical training in onco-hematology for pharmacy technician's working in cytotoxic preparation unit]. / Mise en place d'une formation continue théorique en onco-hématologie au sein d'une unité de préparation des anticancéreux.

OBJECTIVES: Within the context of pharmacy technician's (PT) continuing training (CT), a theoretical instruction in onco-hematology has been developed for PT working in our cytotoxic preparation unit (CPU). The aim of this study is to describe the approach taken, tools used and present knowledge assessment (KA). METHODS: A previous KA has been conducted using quiz available on GERPAC website which listing 36 drugs. Forty-five minutes sessions were conducted. KA was assessing before and after each session and 2 years after. PT appreciation was also evaluated. RESULTS: The previous KA served to targeting gaps and insisted on: indications, mechanism of action and cytotoxic drugs costs. Interactive sessions were led by a pharmacist and concerned about 17 diseases and 3 of the most prescribed cytotoxic drugs: 47 drugs summaries have been written by a pharmacist. The before-after knowledge improvement is significant (P>0.0005) (average [a] before=4.7 vs. a after=9.6). Two years after, this was non-significant but assessment results remain higher than before sessions (a=4.7 vs. 6.8). All PT wish sessions sustainability, 92% reported an adequate comprehension level. CONCLUSION: Lack of time and staff constitute a brake for sustaining and this was also highlighted by other units. Share this experience on a web platform could be interesting. Nevertheless, supports used during sessions should be suitable in conformity with the hospital practice and updated with new therapeutic.

Polymorphisms in Receptors Involved in Opsonic and Nonopsonic Phagocytosis, and Correlation with Risk of Infection in Oncohematology Patients.

High-risk hematological malignancies are a privileged setting for infection by opportunistic microbes, with invasive mycosis being one of the most serious complications. Recently, genetic background has emerged as an unanticipated risk factor. For this reason, polymorphisms for genes encoding archetypal receptors involved in the opsonic and nonopsonic clearance of microbes, pentraxin-3 (PTX3) and Dectin-1, respectively, were studied and correlated with the risk of infection. Fungal, bacterial, and viral infections were registered for a group of 198 patients with high-risk hematological malignancies. Polymorphisms for the pentraxin-3 gene (PTX3) showed a significant association with the risk of fungal infection by Candida spp. and, especially, by Aspergillus spp. This link remained even for patients undergoing antifungal prophylaxis, thus demonstrating the clinical relevance of PTX3 in the defense against fungi. CLEC7A polymorphisms did not show any definite correlation with the risk of invasive mycosis, nor did they influence the expression of Dectin-1 isoforms generated by alternative splicing. The PTX3 mRNA expression level was significantly lower in samples from healthy volunteers who showed these polymorphisms, although no differences were observed in the extents of induction elicited by bacterial lipopolysaccharide and heat-killed Candidaalbicans, thus suggesting that the expression of PTX3 at the start of infection may influence the clinical outcome. PTX3 mRNA expression can be a good biomarker to establish proper antifungal prophylaxis in immunodepressed patients.

[Multiplex ligation-dependent probe amplification in oncohematological diagnostics and research]. / Multiplex ligatiofüggo szondaamplifikáció az onkohematológiai kutatásban és diagnosztikában.

Genetic abnormalities associated with the development, progression and treatment resistance of hematological malignancies are extensively characterized. Rapid, reliable and cost-efficient techniques are needed to screen the clinically relevant aberrations in routine diagnostics. Multiplex ligation-dependent probe amplification is an efficient tool to analyze genomic copy number aberrations at 55-60 different genomic loci. The method allows the profiling of prognostic and predictive markers; thus, it can efficiently be combined with karyotyping and fluorescence in situ hybridization, the most commonly used diagnostic techniques to detect cytogenetic lesions. Furthermore, the method can interrogate methylation status and unravel point mutations at specific sites, providing results in 24 hours. Here, we describe the technical background of multiplex ligation-dependent probe amplification, summarize its advantages and limitations as well as discuss its role in oncohematological diagnostics and research. Finally, future outlook is provided, with emphasis on recent technological advances related to next-generation sequencing. Orv Hetil. 2018; 159(15): 583-592.

Distribution of virulence associated traits among urine Escherichia coli isolates from patients in onco-hematology.

Escherchia coli is the most common etiological agent of urinary tract infections. In this study we had two goals: First of all, to find out if urine stains isolated from our patients--having the particularity of being immunocompromised--would have a virulence genes distribution different from the one observed in strains isolated from ordinary patients. Second, we wanted to identify a common virulence profile associated to these particular strains. The prevalence of virulence factors (VF)-encoding genes was analyzed by PCR. Of the tested VF-encoding genes, malX (80%), ompT (79%), fyuA (74%), usp (67%), chuA (66%), iroN (59%), iutA (56%), papC (36%), pap AH (30%), papEF (28%), hlyA (28%), papG allele II (25%), cnf1 (21%), focG (20%),cvaC (20%) and papG allele III (7%) were significantly associated to urinary strains. Virulence genes distribution of urinary strains isolated from onco-hematology patients and the one observed in strains isolated from ordinary patients are almost the same. The virulence profiles containing adhesins type 1, S and F1C fimbriae, siderophore genes and three individual genes ompT, usp and malX were present in half of the urinary strains and were significantly associated to them. Two virulence signatures occurred significantly in UTI-causing strains (12%). These findings provide first insight into the virulence of UTI-causing E. coli strains isolated in onco-hematology patients.

Microsatellite Typing of Aspergillus flavus Strains in a Tunisian Onco-hematology Unit.

Aspergillus flavus is the most common species associated with invasive aspergillosis in Tunisia. The molecular epidemiology of the species is poorly documented. We used five highly discriminative microsatellite markers for the genotyping of clinical and hospital environmental A. flavus strains to assess whether IA could be hospital-acquired in the onco-hematology unit of the Farhat Hached teaching hospital of Sousse, Tunisia. The genotyping of 18 clinical isolates, collected from sputa of 17 acute leukemia patients, and 81 isolates, collected in these patients' hospital environment and food, identified 57 isolates that were grouped in 10 clones, each of them including 2-17 isolates. The remaining 42 isolates showed a unique genotype. Two main transmission scenarios were observed: (1) the same clone was isolated from different patients; (2) the same clone was isolated from a patient, its hospital environment and/or food. These findings strongly suggest the occurrence of hospital-acquired A. flavus infection/colonization in the investigated onco-hematology unit.

[Study impacto: Descriptive analyzis of pharmacist's clinical practice in onco-hematology]. / Étude impacto : analyse descriptive des pratiques de pharmacie clinique en cancérologie.

Pharmaceutical analyses of chemotherapy prescriptions by hospital pharmacists are activities codified by regulation and rules (bon usage). The involvement of the pharmacists in clinical pharmacy activities in the oncology setting is not clearly identified, justifying the development of a mapping of these activities from a questionnaire addressed to the professionals. One hundred and seven centers have participated to this study at the national level (overall participation rate of 32.4%). More than 95% of them used a computerized ordering system and three quarter of them submit the introduction of new compounds to an analysis by the drug therapeutic committee. Prescription analysis allowed detecting around 2% of errors from the current prescription. Clinical pharmacist participates to tumor boards of onco-hematology (RCP) at a level of 46% for senior pharmacist and 42% for junior pharmacist. This involvement in the RCP allowed anticipating protocol's modification and temporary used authorization. Ninety-two percent of the senior pharmacists estimate that they highlight the risk of no reimbursement for prescription out of the guideline during RCP, resulting to a modification of the prescription for 40% of them. This level of intervention is lower with respectively 64% and 10% for the juniors. This study underlines the expert value of the clinical pharmacist dedicated to oncology setting in pre and post analysis prescriptions. It could be targeted by a prospective analysis of both clinical and pharmacoeconomics impact of these interventions.

Simultaneous merkel cell carcinoma and acute myeloid leukaemia: A diagnostic challenge.

Merkel cell carcinoma is a very aggressive primary skin tumour with a high risk of local recurrences and lymphatic and distant metastases. The frequent association between this carcinoma and other skin tumour and lymphoid malignancies, its similar cellular morphology with leukocytes, and limited infiltration in bone marrow constituted a challenging diagnosis. We report an unusual case of an 82-year-old male who simultaneously presented Merkel cell carcinoma and acute myeloid lymphoma. The diagnosis was established through flow cytometry, immunohistochemical studies and next generation sequencing (NGS) analysis. Flow cytometry allowed for the differentiation of the two cell populations in bone marrow aspirate, which was crucial to the diagnosis of Merkel cell carcinoma and acute myeloid leukaemia (AML), after confirmed by immunohistochemistry. AML could be classified based on NGS results. Following diagnosis, the patient received palliative care and died 50 days later. immunophenotypic analysis by flow cytometry and Immunohistochemical study was crucial to establish the diagnosis of simultaneous affection of Merkel cell carcinoma and hematologic disorder.

Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors: A case report and literature analysis.

Hepatitis B virus (HBV) reactivation (HBVr) represents a severe and potentially life-threatening condition, and preventive measures are available through blood test screening or prophylactic therapy administration. The assessment of HBVr traditionally considers factors such as HBV profile, including hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen, along with type of medication (chemotherapy; immunomodulants). Nevertheless, consideration of possible patient's underlying tumor and the specific malignancy type (solid or hematologic) plays a crucial role and needs to be assessed for decision-making process.

Safety of empirical antibiotic therapy discontinuing for fever of unknown origin during high-risk neutropenia in children.

BACKGROUND: ECIL-2021 recommends discontinuing empirical antibiotic therapy (EAT) in febrile-neutropenic children after 72 h of treatment and at least 24-48 h of apyrexia in the case of fever of unknown origin (FUO). These guidelines are rarely applied to high-risk children's neutropenia. MATERIAL AND METHODS: We retrospectively included all consecutive FUO episodes occurring during profound neutropenia ≥ 10 days in children in our institution. We evaluated the safety of EAT discontinuation in patients for whom the ECIL guidelines were followed compared to those for whom they didn't. We used a combined criterion of mortality and intensive care unit admission at 30 days. We identified risk factors for recurrent fever after EAT discontinuation. RESULTS: Fifty-one FUO episodes occurred in 37 patients. EAT discontinuation followed ECIL guidelines in 19 (37 %) episodes. No deaths and-or transfers in ICU occurred in the ECIL group. The duration of EAT was shorter by nine days in the group following ECIL guidelines (p < 0.001). We observed 14 (27 %) episodes of recurrent fever. Mucositis was significantly associated with recurrent fever (p < 0.01). CONCLUSION: EAT discontinuation seems feasible and safe in FUO during prolonged febrile neutropenia in children. However, mucosal lesions should prompt thorough surveillance due to the risk of recurrent fever.

Development and Implementation of an eHealth Oncohematonootric Program: Descriptive, Observational, Prospective Cohort Pilot Study.

BACKGROUND: In oncohematology, both the development of the disease and the side effects of antineoplastic treatment often take a toll on patients' physical and nutritional well-being. In this era of digital transformation, we launched a pioneering project for oncohematologic patients to promote adherence to a healthy lifestyle and improve their physical and nutritional well-being. We aim to achieve this goal by involving doctors and nutritionists through the Nootric app. OBJECTIVE: This study aims to assess the impact of the use of eHealth tools to facilitate nutrition and well-being in oncohematologic patients. We also aim to determine the usefulness of physical-nutritional management in improving tolerance to chemotherapy treatments within routine clinical practice. METHODS: We designed a descriptive, observational, longitudinal, prospective cohort pilot study that included a total of 22 patients from March to May 2022 in the Vinalopó University Hospital. The inclusion criteria were adults over 18 years of age diagnosed with oncohematological pathology in active chemotherapy treatment. An action plan was created to generate alerts between the doctor and the nutritionist. In the beginning, the patients were trained to use the app and received education highlighting the importance of nutrition and physical exercise. Sociodemographic, clinical-biological-analytical (eg, malnutrition index), health care impact, usability, and patient adherence data were collected. Tolerance to chemotherapy treatment and its health care impact were evaluated. RESULTS: We included 22 patients, 11 (50%) female and 11 (50%) male, ranging between 42 and 84 years of age. Among them, 13 (59%) were adherents to the program. The most frequent diseases were lymphoproliferative syndromes (13/22, 59%) and multiple myeloma (4/22, 18%). Moreover, 15 (68%) out of 22 patients received immunochemotherapy, while 7 (32%) out of 22 patients received biological treatment. No worsening of clinical-biological parameters was observed. Excluding dropouts and abandonments (n=9/22, 41%), the adherence rate was 81%, established by calculating the arithmetic mean of the adherence rates of 13 patients. No admission was observed due to gastrointestinal toxicity or discontinuation of treatment related to alterations in physical and nutritional well-being. In addition, only 5.5% of unscheduled consultations were increased due to incidents in well-being, mostly telematic (n=6/103 consultation are unscheduled). Additionally, 92% of patients reported an improvement in their nutritional habits (n=12/13), and up to 45% required adjustment of medical supportive treatment (n=5/11). There were no cases of grade 3 or greater gastrointestinal toxicity. All of this reflects improved tolerance to treatments. Patients reported a satisfaction score of 4.3 out of 5, while professionals rated their satisfaction at 4.8 out of 5. CONCLUSIONS: We demonstrated the usefulness of integrating new technologies through a multidisciplinary approach. The Nootric app facilitated collaboration among the medical team, nutritionists, and patients. It enabled us to detect health issues related to physical-nutritional well-being, anticipate major complications, and mitigate potentially avoidable risks. Consequently, there was a decrease in unscheduled visits and admissions related to this condition.

The Relationship between Gene Polymorphisms od the XRCC1 and TP53 with the Gender of Children with Acute Leukemia.

BACKGROUND: The relevance of the study lies in the fact that although the role of polymorphism of some genes that are responsible for cell apoptosis and deoxyribonucleic acid repair in the development of acute leukemia has already been established, its relationship with the gender of patients has not been studied enough. This study was aimed at studying the relationship between the Arg399Gln polymorphism in the XRCC1 deoxyribonucleic acid repair gene and the Arg72Pro polymorphism in the TP53 tumor suppressor gene encoding the p53 protein with the gender of children with acute leukemia. MATERIAL AND METHODS: The study included 100 newly diagnosed pediatric patients of Kyrgyz nationality (69 boys and 31 girls), among which there were 77 patients with acute lymphoblastic leukemia, 22 patients with acute myeloblastic leukemia and 1 patient with a biphenotypic variant. Determination of polymorphisms was carried out by PCR-RFLP analysis or polymerase chain reaction followed by an analysis of restriction fragment length polymorphism. The interrelation of the results obtained with the patients' gender was assessed using statistical methods. RESULTS: The study showed that there were no gender differences for all three genotypes of the Arg72Pro polymorphic marker of the tumor suppressor p53 (ТР53). Three Arg399Gln genotypes of the XRCC1 gene also did not depend on gender. However, with a separate analysis of each polymorphism, there was a tendency for a greater proportion of the Arg/Gln genotype in the group of boys compared to girls. The Gln/Gln polymorphism relationship requires further study due to insufficient data for analysis. CONCLUSION: The study has expanded the understanding of genetic changes and their relationship with gender, which have diagnostic, prognostic and therapeutic implications in acute leukemia. The conducted research of the relationship between individual phenotypes of acute lymphoblastic leukemia with risky polymorphisms in some genes contributes to the study of AL.

Aminoglycosides' dosage in hematological malignancies and febrile neutropenia: extended interval or conventional dosage?

A patient with acute myeloid leukemia presented various episodes of febrile neutropenia, for which there was no positive response to antibiotic treatments. Following an episode of bacteremia by extensively drug-resistant Klebsiella pneumoniae, amikacin was prescribed, pharmacokinetic analyses of its plasma concentrations were performed and the dosage interval was narrowed to 12 and 8 h in order to counteract the reduced postantibiotic effect due to the patient being immunocompromised. The patient responded positively, with procalcitonin decreasing and body temperature normalizing. Recovery was finally achieved, without renal or auditory damage. This case proposes tightening dosage intervals for aminoglycosides as an effective strategy in immunocompromised patients. Aminoglycosides are given over extended intervals (24 h), considering concentration-dependent effectiveness, nephrotoxicity and postantibiotic effect. Leukocytes appear to play a determining role in the postantibiotic effect, with no proposed dosing strategy for strongly immunocompromised patients.

Invasive fungal infections in patients with hematologic malignancies (aurora project): lights and shadows during 18-months surveillance.

The aim of this multicenter prospective study was to evaluate the incidence of invasive fungal infections (IFIs) in adult and pediatric patients with hematologic malignancies, involving nine nosocomial facilities in Southern Italy over a period of 18 months. Furthermore, results of an environmental microbial surveillance routinely carried out in some of the enrolled hospitals are reported. A total of 589 onco-hematological patients were enrolled and 27 IFIs were documented. The main infections were caused by yeasts, more than filamentous fungi (overall incidence of 2.7% and 1.9%, respectively). The yeasts were mainly represented by Candida spp. (87.5%), all isolated by blood cultures; C. parapsilosis was the most common species. Among mould infections, the most frequent site was the lung, with regard to aspergillosis (81.8%). In six of the 10 patients with suspected aspergillosis, the diagnosis was made by the detection of galactomannan and (1,3)-ß-d-glucan antigens. The microbiological surveillance carried out on 156 air, 312 water and 312 surface samples revealed low environmental contamination: Alternaria alternata was the only fungus isolated from two surface samples. Our data, especially the low occurrence of filamentous fungi, suggest a particular local epidemiology. Further studies are needed to confirm this microbiological trend in onco-hematological patients in Southern Italy, the results of which might be helpful to improve the management of these patients.

Application of Machine Learning Methods for Epilepsy Risk Ranking in Patients with Hematopoietic Malignancies Using.

Machine learning methods to predict the risk of epilepsy, including vascular epilepsy, in oncohematological patients are currently considered promising. These methods are used in research to predict pharmacoresistant epilepsy and surgical treatment outcomes in order to determine the epileptogenic zone and functional neural systems in patients with epilepsy, as well as to develop new approaches to classification and perform other tasks. This paper presents the results of applying machine learning to analyzing data and developing diagnostic models of epilepsy in oncohematological and cardiovascular patients. This study contributes to solving the problem of often unjustified diagnosis of primary epilepsy in patients with oncohematological or cardiovascular pathology, prescribing antiseizure drugs to patients with single seizure syndromes without finding a disease associated with these cases. We analyzed the hospital database of the V.A. Almazov Scientific Research Center of the Ministry of Health of Russia. The study included 66,723 treatment episodes of patients with vascular diseases (I10-I15, I61-I69, I20-I25) and 16,383 episodes with malignant neoplasms of lymphoid, hematopoietic, and related tissues (C81-C96 according to ICD-10) for the period from 2010 to 2020. Data analysis and model calculations indicate that the best result was shown by gradient boosting with mean accuracy cross-validation score = 0.96. f1-score = 98, weighted avg precision = 93, recall = 96, f1-score = 94. The highest correlation coefficient for G40 and different clinical conditions was achieved with fibrillation, hypertension, stenosis or occlusion of the precerebral arteries (0.16), cerebral sinus thrombosis (0.089), arterial hypertension (0.17), age (0.03), non-traumatic intracranial hemorrhage (0.07), atrial fibrillation (0.05), delta absolute neutrophil count (0.05), platelet count at discharge (0.04), transfusion volume for stem cell transplantation (0.023). From the clinical point of view, the identified differences in the importance of predictors in a broader patient model are consistent with a practical algorithm for organic brain damage. Atrial fibrillation is one of the leading factors in the development of both ischemic and hemorrhagic strokes. At the same time, brain infarction can be accompanied both by the development of epileptic seizures in the acute period and by unprovoked epileptic seizures and development of epilepsy in the early recovery and in a longer period. In addition, a microembolism of the left heart chambers can lead to multiple microfocal lesions of the brain, which is one of the pathogenetic aspects of epilepsy in elderly patients. The presence of precordial fibrillation requires anticoagulant therapy, the use of which increases the risk of both spontaneous and traumatic intracranial hemorrhage.

Liquid Biopsy in Cancer: Focus on Lymphoproliferative Disorders.

Within the context of precision medicine, the scientific community is giving particular attention to early diagnosis and intervention, guided by non-invasive methodologies. Liquid biopsy (LBx) is a recent laboratory approach consisting of a non-invasive blood draw, which allows the detection of information about potential prognostic factors, or markers to be used for diagnostic purposes; it might also allow the clinician to establish a treatment regimen and predict a patient's response. Since the discovery of circulating tumor cells (CTCs) in the nineteenth century, the possibility of integrating LBx into clinical practice has been explored, primarily because of its safeness and easy execution: indeed, compared to solid biopsy, sampling-related risks are less of a concern, and the quickness and repeatability of the process could help confirm a prompt diagnosis or to further corroborate the existence of a metastatic spreading of the disease. LBx's usefulness has been consolidated in a narrow range of oncological settings, first of all, non-small cell lung carcinoma (NSCLC), and it is now gradually being assessed also in lymphoproliferative diseases, such as acute lymphocytic leukemia (ALL), B-cell lymphomas, and multiple myeloma. The present review aims to summarize LBx's overall characteristics (such as its advantages and flaws, collection and analysis methodologies, indications, and targets of the test), and to highlight the applications of this technique within the specific field of B-cell malignancies. The perspectives on how such a simple and convenient technique could improve hemato-oncological clinical practice are broadly encouraging, yet far from a complete integration in routine clinical settings.