Conclusion

This concluding chapter highlights the efforts put into reducing tax crimes. It starts with the socio-economic impact of the COVID-19 pandemic on budget deficits and optimisation of tax collection and reducing the tax gap. The Anti-Money Laundering (AML) framework and anti-tax fraud framework in the EU laid the foundation for future legislation and policy to counter tax crimes across Europe. Case studies, focus groups, and workshops found that interagency and international cooperation in fighting tax crimes fronted significant constraints, such as data exchange, joint investigations, collaborative asset confiscations, and sanctions. The chapter then discusses the findings from the PROTAX project to expound its point on legal regimes being made across Europe. It suggests that developing a holistic tax enforcement eco-system is needed instead of just tinkering with legal provisions. © U Turksen, D Vozza, R Kreissl, and F Rasmouki 2023.

A new tractable method for generating human alveolar macrophage-like cells in vitro to study lung inflammatory processes and diseases.

Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAMs) to pulmonary diseases remains poorly understood due to the difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, that is, Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (granulocyte macrophage colony-stimulating factor, transforming growth factor-ß, and interleukin 10) that facilitate the conversion of blood-obtained monocytes to an AM-like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.IMPORTANCEMillions die annually from respiratory disorders. Lower respiratory track gas-exchanging alveoli maintain a precarious balance between fighting invaders and minimizing tissue damage. Key players herein are resident AMs. However, there are no easily accessible in vitro models of HAMs, presenting a huge scientific challenge. Here, we present a novel model for generating AML cells based on differentiating blood monocytes in a defined lung component cocktail. This model is non-invasive, significantly less costly than performing a bronchoalveolar lavage, yields more AML cells than HAMs per donor, and retains their phenotype in culture. We have applied this model to early studies of M. tuberculosis and SARS-CoV-2. This model will significantly advance respiratory biology research.

Defective T-cell response to COVID-19 vaccination in acute myeloid leukaemia and myelodysplastic syndromes.

Limited data exist on COVID-19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS-EB2). We report results from a prospective study, PACE (Patients with AML and COVID-19 Epidemiology). 93 patients provided samples post-vaccine 2 or 3 (PV2, PV3). Antibodies against SARS-COV-2 spike antigen were detectable in all samples. Neutralization of the omicron variant was poorer than ancestral variants but improved PV3. In contrast, adequate T-cell reactivity to SARS-COV-2 spike protein was seen in only 16/47 (34%) patients PV2 and 23/52 (44%) PV3. Using regression models, disease response (not in CR/Cri), and increasing age predicted poor T cell response.

Influenza A (H1N1) virus induced long-term remission in a refractory acute myeloid leukaemia.

There have been reports of haematological cancer patients achieving spontaneous remission after being infected with the influenza A or SARS-COV-2 virus. Here, we present the first case of long-term complete remission (CR) induced by influenza A (IAV, H1N1 subtype) in a refractory AML patient and have functionally validated this finding in two different animal disease models. We observed a significant increase in the proportion of helper T cells in the patient after IAV infection. The levels of cytokines, including IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α, were higher in IAV-infected patients compared with control groups. These findings indicate that the anti-tumour effects induced by IAV are closely related to the modification of the immune response. Our study provides new evidence of the anti-tumour effects of IAV from a clinical practice perspective.

Diagnostic and Treatment Obstacles in Acute Myeloid Leukemia: Social, Operational, and Financial.

Acute myeloid leukemia (AML) can affect individuals of all ages, but is more common in older adults. It has been estimated that AML accounted for 1% of all newly diagnosed cancers in the USA in 2022. The diagnostic process varies depending on the presenting symptoms and the healthcare facility that patients attend at diagnosis. The treatment process is long and prone to complications, requiring experienced medical professionals and appropriate infrastructure. Treatment of the disease did not change greatly over the years until 2017 when targeted therapies were licensed. The treatment of AML is associated with significant direct economic costs. A number of obstacles originating both from individual patients and the healthcare system may be encountered during the diagnosis and treatment of the disease, which may negatively impact the optimal management of the disease process. In this article, we focus primarily on the social, operational, and financial obstacles including the corona virus disease 2019 (COVID-19) pandemic experienced during the diagnosis and treatment of AML.

The Globalization of Cashless Transactions Using Blockchain Technology to Preventing Money Laundering and the Changing Trends in the Cryptocurrency Market: A Learning Experience of Polish and EU Laws

Summary The COVID-19 pandemic experience has driven us to rely on technology so much on the development and expansion of technology, including cashless transactions. Criminal groups may become more interested in electronic payments and virtual currencies because of increased traffic in these areas. When comparing the second half of the 2019 to the first half of the 2020, the number of fraudulent card transactions increased by 11.4%. New developments in virtual currency trading regulations, including the digital finance package, which includes, among other things, a draught regulation from the European Parliament and an amended act to combat money laundering and terrorist financing, among others. For the reasons stated above, these regulations may lead to a virtual currency market collapse and the withdrawal of investors and the siphoning of money into Asian markets as a result. The current regulations are a manifestation of total regulation and do not encourage technological advancement. © 2022 Abhishek Thommandru et al., published by Sciendo.

Giant Cellulitis-Like Sweet Syndrome Masquerading As Cellulitis and Shingles: A Case Report and Literature Review.

Sweet syndrome (SS) is also known as acute febrile neutrophilic dermatoses. Clinically, SS features fever, arthralgias, and the sudden onset of an erythematous rash. The morphologies of skin lesions in SS are heterogenous, varying from papules, plaques, and nodules to hemorrhagic bullae, which sometimes makes the diagnosis of SS more challenging. We report a 62-year-old obese male with a history of chronic myeloid leukemia in remission for 10 years who presented with a rash for five days. The patient reported prodromal flu-like symptoms with subjective fever, malaise, cough, and nasal congestion followed by a sudden onset, painful, non-pruritic rash. The rash was associated with bilateral hip arthralgias and abdominal pain. The patient denied any recent travel, exposure to sick contacts, or the use of any new medications. Physical examination showed a well-demarcated, non-blanching, confluent, erythematous plaque involving the bilateral buttocks and extending to the lower back and flanks with coalescent "juicy"-appearing plaques and flaccid bullae. No oral or mucosal involvement was noted. Laboratory investigations revealed mild leukocytosis, elevated inflammatory markers, and acute kidney injury. The patient was started on antibiotics given the cellulitis-like skin lesions, leukocytosis with neutrophilia, and elevated inflammatory markers. Dermatology was consulted, who attributed the patient's rash to shingles and recommended initiating acyclovir and obtaining a skin biopsy. However, the patient's rash and arthralgias worsened with anti-viral treatment while awaiting pathology results. Antinuclear antibodies, complement, human immunodeficiency virus, hepatitis panel, blood cultures, and tumor markers were all negative. Flow cytometry showed no evidence of hematopoietic neoplasms. The skin punch biopsy revealed dense neutrophilic infiltration in the dermis with no evidence of leukocytoclastic vasculitis, consistent with acute neutrophilic dermatoses. The diagnosis of giant cellulitis-like Sweet syndrome was established, and the patient was started on prednisone 60 milligrams daily. His symptoms improved promptly with steroid treatment. Our case suggests that SS can camouflage a wide spectrum of diseases, including cellulitis, shingles, vasculitis, drug eruptions, leukemia cutis, and sarcoidosis, which emphasizes the importance of keeping a high index of suspicion for SS when assessing the clinical constellations of fever, neutrophilia, and erythematous plaques suggesting atypical cellulitis. Approximately 21% of Sweet syndrome is associated with malignancy. Sweet syndrome can precede, concur with, or follow the onset of malignancy. Due to the lack of a systematic approach to patients with SS, under-investigation and diagnostic delays are common. Therefore, further screening and continuous monitoring in patients with SS becomes especially important in facilitating the early detection of a potential underlying malignancy and assists in initiating adequate therapy.

Adversarial Machine Learning Protection Using the Example of Evasion Attacks on Medical Images

This work considers evasion attacks on machine learning (ML) systems that use medical images in their analysis. Their systematization and a practical assessment of feasibility are carried out. Existing protection techniques against ML evasion attacks are presented and analyzed. The features of medical images are given and the formulation of the problem of evasion attack protection for these images based on several protective methods is provided. The authors have identified, implemented, and tested the most relevant protection methods on practical examples: an analysis of images of patients with COVID-19.

Patient, Family Member and Physician Perspectives and Experiences with AML Treatment Decision-Making.

INTRODUCTION: Treatment decisions in older adults with acute myeloid leukemia (AML) are challenging, particularly for those who are not candidates for intensive chemotherapy (IC), and the trade-offs patients, their families and physicians consider when choosing a treatment option are not well understood. This qualitative research explored the value of extending survival and the treatment decision-making process from a multi-stakeholder perspective. METHODS: Overall, 28 patients with AML (≥ 65 years old, unsuitable for IC), 25 of their relatives and 10 independent physicians from the US, UK and Canada took part in one-on-one, 60-minute qualitative interviews. RESULTS: Across all stakeholders, improved health-related quality of life (HRQoL), extended survival and relief of AML symptoms were recognized as most important in AML treatment decision-making. However, extending survival in 'good health' was more important than extending survival alone, particularly because of the extra time it gives patients and their relatives together, and allows patients to achieve important goals. Patients' limited understanding of available treatment options, paired with incorrect perceptions of treatment side effects, impacted their involvement in the treatment decision-making process. Patients and physicians perceived physicians to have the most influence in the decision-making process despite their priorities not always aligning. CONCLUSION: These findings illustrate the importance of having structured discussions which explicitly assess patients' goals and their understanding and expectations of treatments and also the need for patient friendly resources about the lived experience of AML and available treatment options. These measures will help to ensure that patients are fully involved in the shared decision-making process.

Unusual Presentation of Acute Myeloid Leukemia (AML-M2): A Case Report

Context: Acute myeloid leukemia (AML) is rarely presented with thrombocytosis and marked thrombocytosis with a platelet count over 1.0×1012/L is an extremely rare phenomenon. Objective: A case of de novo AML with unusual presentation by extreme thrombocytosis. Design: A case report. Setting: Hematology Unit at the Oncology Center Mansoura University, Egypt. Patient: A 37-year-old male patient with a history of sleeve gastrectomy in 2020, presented with oral mucositis, recurrent abscess, fever, and bilateral axillary lymphadenopathy. Initial complete blood count (CBC) showed a Hb level of 6 g/dL, a platelet count of 1.685×109/L, and a white blood cell (WBC) count of 19×109/L. Diagnosis of de novo AML (FAB-M2 AML) was confirmed by bone marrow aspiration, biopsy, and immunophenotyping. Cytogenetic study showed negative t(8;21)/inv 16/ t(9;22). A molecular study showed positive FLT-3 mutation and negative BCP/ABL1, JAK2, V617F, and CALR exon 9 mutations excluding blast transformation on top of myeloproliferative neoplasm (MPN) and myelodysplastic syndrome (MDS). Interventions: The patient received induction chemotherapy including a course of 7-day-cytarabine along with 3-day-anthracycline on September 20th, 2021 but the patient was refractory as BMA showed blast cells 75%. The patient started salvage HAM (high-dose cytosine arabinoside and mitoxantrone) + Sorafenib on November 6th, 2021. Again, he could not achieve a response and received FLAG (high-dose cytosine arabinoside, fludarabine, and granulocyte colony-stimulating factors) + Sorafenib on December 18th, 2021, after recovery from COVID-19 infection. Main Outcome Measures: To shed light on fact that myeloid neoplasms as MPN, MDS, and de novo AML can share overlapping features. Results: On January 25th, 2022, the last CBC showed a Hb level of 8.4 g/dL, a platelet Count of 395×109/L, and a WBC Count of 2.41×109/L with a differential Neutrophil count of 0.24×109/L. The patient lost follow-up since then. Conclusions: Only a few AML cases have been reported with thrombocytosis. Detailed molecular studies are mandatory to confirm the diagnosis of de novo AML patients with unusual presentation. Careful follow-up of those cases could help in establishing management guidelines for better outcomes as those patients usually have a poor prognosis.

Coexistence of COVID-19 and AML-M5: A Pediatric Case Report COVID-19 ve AML-M5 Birlikteliği: Bir Pediyatrik Olgu Raporu

Coronavirus disease-2019 (COVID-19) is an infection that firstly reported in China and spread rapidly and caused a pandemic all over the world and still continues to spread. Although lung infection is the main factor affecting mortality, it can creates multisystemic involvement. Even though the clinical course is relatively mild in children, it is more severe in patients who have underlying chronic disease. A 16-year-old patient, who was previously followed up due to Familial Mediterranean Fever, was admitted to the emergency department with cough and respiratory distress, and in the evaluation of the patient, to the best our knowledge, the first case in the literature was diagnosed with pneumonia due to COVID-19 and AML-M5, simultaneously. Even if there are signs of viral infection and laboratory tests suggestive of COVID-19, the changes of hematological parameters should be examined in terms of malignancy. © 2022 by Society of Pediatric Emergency and Intensive Care Medicine.

Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant: SARS-CoV-2 Vaccine as a Potential Trigger.

Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are at a risk of developing immune-mediated tissue damage from activation of the donor's immunocompetent T cells by the recipient's normally expressed antigens, a phenomenon called graft-versus-host disease (GVHD). With the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), new vaccines have been developed to prevent morbidity and mortality, including the highly vulnerable hematologic malignancy patients after undergoing AHSCT. The early pathophysiologic events in GVHD include priming the donor T cells with molecules that are endogenous or pathogenic. In this case series, we present two cases of AHSCT recipients in which the SARS-CoV-2 vaccination series proceeded the development of GVHD manifesting with oral mucosal symptoms and derangement in the liver function tests. Our experience raises the question if any of the vaccine components serve as a molecular trigger for GVHD, making the current SARS-CoV-2 vaccines a risk factor for activating the immune system and developing GVHD.

A Case Series of SARS-CoV-2 Omicron Variant in Patients With Acute Leukemia.

Coronavirus disease 2019 (COVID-19) is a respiratory viral illness caused by coronavirus 2 (SARS-CoV-2). The disease often presents with non-specific symptoms, including fever, and fatigue, usually associated with respiratory symptoms (eg., cough) and other systemic involvement. The primary strategy to prevent transmission and reduce the disease severity of the SARS-CoV-2 infection is through vaccination. However, the virus had shown significant changes and mutations that resulted in the emergence of different strains. Each strain varies in its virulence, disease severity, and the body's immune system response. Previous reports showed that the Omicron variant causes mild disease. Little is known about the effect of Omicron in patients with acute leukemia. We present three patients with acute leukemia who had an infection with the Omicron variant of the SARS-CoV-2 virus.

The Venetoclax/Azacitidine Combination Targets the Disease Clone in Acute Myeloid Leukemia, Being Effective and Safe in a Patient with COVID-19.

The addition of Venetoclax (VEN) to Hypomethylating agents (HMAs) significantly improves the probability of complete remission and prolongs survival in patients with Acute Myeloid Leukemia (AML) when compared to HMA alone. However, the mutated clone composition may impact the probability of response and its duration. Here, we describe the molecular profile of a patient with AML rapidly evolved from a previous therapy-related-Chronic MyeloMonocytic Leukemia, who achieved safely complete remission after treatment with the VEN/Azacitidine combination, even in the presence of SARS-COVID-2 infection. The targeted NGS analysis showed that the VEN/AZA combination led to the eradication of the FLT3-ITD and RUNX1 mutated clone/s primarily associated with AML evolution, and subsequently, the SRSF2, NRAS, and ASXL1 mutated clone/s. This case also underlines the importance of the sequential use of targeted NGS for disease monitoring: the deep molecular remission achieved by this patient allowed to safely guide adjustments of drug dosage and treatment intervals in the presence of neutropenia, helping to rule out disease progression.

Spontaneous hyphema in the setting of COVID-19 pneumonia.

PURPOSE: To report a challenging case of spontaneous hyphema in the setting of prone positioning for COVID-19 pneumonia. OBSERVATIONS: A previously healthy patient was concomitantly diagnosed with acute myelogenous leukemia (AML) and COVID-19 infection. During his hospitalization he required intubation and prone positioning. Following change from prone to supine positioning, he was noted to have developed a large unilateral spontaneous hyphema. CONCLUSIONS AND IMPORTANCE: We present a challenging case of spontaneous hyphema due to a hematologic malignancy in the setting of prone positioning for COVID-19 pneumonia.

Could COVID-19 induce remission of acute leukemia?

BACKGROUND: COVID-19 viral pandemic caused many mortalities in cancer patients especially those with hematological malignancies. The immunological response to COVID-19 infection is responsible for the outcome of cases whether mild, severe or critical. CASE PRESENTATION: Two cases presented with moderate COVID-19 viral infection, concomitant with acute myeloid leukemia and T acute lymphoblastic leukemia, respectively. Surprisingly, after the administration of COVID-19 supportive therapy, the cases showed disease remission after a follow-up period of 12 and 5 months, respectively. Additionally, the blast cells dropped to only 3% and 0% in the bone marrow aspirates of those two cases, respectively, after it was 30% in both cases at diagnosis. CONCLUSION: The immune response that emerged against COVID-19 infection could potentially produce anti-tumor immunity in some patients, or the virus may act as an oncolytic virus. However, further investigations are required to explain this phenomenon, which may help in finding a possible new targeted therapy for these cases.

First report of invasive Aspergillus rhinosinusitis in a critically ill COVID-19 patient affected by acute myeloid leukemia, northeastern Iran.

This is a report of established invasive Aspergillus rhinosinusitis in a patient diagnosed with COVID-19 and afflicted by AML, which was initially considered to be rhinocerebral mucormycosis.