Three-year cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia or small cell lymphocytic lymphoma treated with Bruton tyrosine kinase inhibitors acalabrutinib or ibrutinib: a real-world analysis.

Bruton tyrosine kinase (BTK) inhibitors play an important role in targeted treatment of B-cell lymphoproliferative disorders. However, adverse events may limit the proper course of treatment in many patients. The purpose of this study is to compare the risk of cardiovascular and non-cardiovascular adverse events in patients with chronic lymphocytic leukemia (CLL) or small cell lymphocytic lymphoma (SLL) treated with the first-generation BTK inhibitor ibrutinib versus second-generation acalabrutinib, using real-world data from a collaborative multinational network. We used data from the network (TriNetX), which encompasses more than 100 healthcare organizations worldwide. We queried the database for patients aged ≥ 18 years with chronic lymphocytic leukemia or small-cell lymphomas treated with ibrutinib or acalabrutinib in the past ten years before the analysis. We used propensity score matching to balance the cohorts. The 3-year cumulative incidences and hazard ratios for the following outcomes were calculated: atrial flutter or fibrillation, other arrhythmias, heart failure, ischemic stroke or peripheral embolism, acute coronary syndrome, bleeding, and sepsis. We compared 2,107 patients in each group. Atrial fibrillation or flutter occurred in 150 (7.1%) patients with acalabrutinib and 310 (14.7%) patients with ibrutinib during the 3-year follow-up (hazard ratio, 0.68, 95% CI 0.55-0.84). New-onset hypertension occurred in 342 (16.3%) patients in the acalabrutinib group and 584 (27.7%) patients in the ibrutinib group (hazard ratio 0.81, 95% CI 0.66-0.98). Sepsis was diagnosed in 136 (6.5%) patients in the acalabrutinib group versus 239 (11.3%) patients in the ibrutinib group (hazard ratio 0.77, 95 CI 0.60-0.98). The two groups had no significant differences concerning the other adverse events. In a large retrospective cohort using real-world data from electronic medical registers, patients with CLL or SLL treated with acalabrutinib had a better cardiovascular and non-cardiovascular safety profile than those treated with ibrutinib, with lower risks of atrial flutter or fibrillation, new-onset arterial hypertension, and sepsis.

Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

Cancer risk-reducing surgery: Brazilian Society of Surgical Oncology Guideline Part 2 (Gastrointestinal and thyroid).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Eleven questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reducing colectomy, gastrectomy, and thyroidectomy, a major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO and it should serve as an important reference for the management of families with cancer predisposition.

Characterizing the Interaction between Root-knot Nematodes and Soil-borne Fungi which are Pathogenic to Passion Fruit (Passiflora Edulis).

For decades there have been anecdotal claims of synergistic interactions between plant-parasitic nematodes and soil-borne fungi causing decline of productivity of passion fruit (Passiflora edulis) orchards. An empirical confirmation of these disease complexes would impact disease management and plant breeding for resistance. To test those claims, we subjected passion fruit plants to single or concomitant parasitism by Meloidogyne javanica or M. incognita and Fusarium nirenbergiae or Neocosmospora sp. under controlled conditions. Non-inoculated plants served as control for the assays. The severity of shoot symptoms and variables related to plant growth, the extent of fungal lesions, and nematode reproduction were assessed to characterize the interactions. The shoot symptoms and effect on plant growth induced by the pathogens varied, but no synergy between the pathogens was observed. Moreover, the volume of tissue lesioned by the fungi was not affected by co-parasitism of the nematodes. Conversely, plant resistance to the nematodes was not affected by co-parasitism of the fungi. The interactions M. incognita-F. nirenbergiae, M. incognita-Neocosmospora sp., M. javanica-F. nirenbergiae, and M. javanica-Neocosmospora sp. were not synergistic as previously claimed, but instead neutral.

Search for Sub-Solar Mass Binaries with Einstein Telescope and Cosmic Explorer.

A possible detection of sub-solar mass ultra-compact objects would lead to new perspectives on the existence of black holes that are not of astrophysical origin and/or pertain to formation scenarios of exotic ultra-compact objects. Both possibilities open new perspectives for better understanding of our universe. In this work, we investigate the significance of detection of sub-solar mass binaries with components mass in the range: 10-2M⊙ up to 1M⊙, within the expected sensitivity of the ground-based gravitational waves detectors of third generation, viz., the Einstein Telescope (ET) and the Cosmic Explorer (CE). Assuming a minimum of amplitude signal-to-noise ratio for detection, viz., ρ=8, we find that the maximum horizon distances for an ultra-compact binary system with components mass 10-2M⊙ and 1M⊙ are 40 Mpc and 1.89 Gpc, respectively, for ET, and 125 Mpc and 5.8 Gpc, respectively, for CE. Other cases are also presented in the text. We derive the merger rate and discuss consequences on the abundances of primordial black hole (PBH), fPBH. Considering the entire mass range [10-2-1]M⊙, we find fPBH<0.70 (<0.06) for ET (CE), respectively.

Halogen Bonding: An Underestimated Player in Membrane-Ligand Interactions.

Halogen bonds (XBs) are noncovalent interactions where halogen atoms act as electrophilic species interacting with Lewis bases. These interactions are relevant in biochemical systems being increasingly explored in drug discovery, mainly to modulate protein-ligand interactions, but are also found in engineered protein or nucleic acid systems. In this work, we report direct evidence for the existence of XBs in the context of biological membrane systems, thus expanding the scope of application of these interactions. Indeed, our molecular dynamics simulations show the presence of favorable interactions between halobenzene derivatives and both phosphate or ester oxygen acceptors from a model phospholipid bilayer, thus supporting the existence of XB-mediated phospholipid-halogen recognition phenomena influencing the membrane insertion profile of the ligands and their orientational preferences. This represents a relevant interaction, previously overlooked, eventually determining the pharmacological or toxicological activity of halogenated compounds and hence with potential implications in drug discovery and development, a place where such species account for a significant part of the chemical space. We also provide insights into a potential role for XBs in the water-to-membrane insertion of halogenated ligands as XBs are systematically observed during this process. Therefore, our data strongly suggest that, as the ubiquitous hydrogen bond, XBs should be accounted for in the development of membrane partition models.

Reassessing Patterns of Response to Immunotherapy with PET: From Morphology to Metabolism.

Cancer demands precise evaluation and accurate and timely assessment of response to treatment. Imaging must be performed early during therapy to allow adjustments to the course of treatment. For decades, cross-sectional imaging provided these answers, showing responses to the treatment through changes in tumor size. However, with the emergence of immune checkpoint inhibitors, complex immune response patterns were revealed that have quickly highlighted the limitations of this approach. Patterns of response beyond tumor size have been recognized and include cystic degeneration, necrosis, hemorrhage, and cavitation. Furthermore, new unique patterns of response have surfaced, like pseudoprogression and hyperprogression, while other patterns were shown to be deceptive, such as unconfirmed progressive disease. This evolution led to new therapeutic evaluation criteria adapted specifically for immunotherapy. Moreover, inflammatory adverse effects of the immune checkpoint blockade were identified, many of which were life threatening and requiring prompt intervention. Given complex concepts like tumor microenvironment and novel therapeutic modalities in the era of personalized medicine, increasingly sophisticated imaging techniques are required to address the intricate patterns of behavior of different neoplasms. Fluorine 18-fluorodeoxyglucose PET/CT has rapidly emerged as one such technique that spans both molecular biology and immunology. This imaging technique is potentially capable of identifying and tracking prognostic biomarkers owing to its combined use of anatomic and metabolic imaging, which enables it to characterize biologic processes in vivo. This tailored approach may provide whole-body quantification of the metabolic burden of disease, providing enhanced prediction of treatment response and improved detection of adverse events. ©RSNA, 2020.

Emergency CT of abdominal complications of ingested fish bones: what not to miss.

Fish bones are the most commonly ingested structures and the most common cause of foreign body perforation of the gastrointestinal tract (GIT). Clinical presentation of foreign body GIT perforation is nonspecific, in many cases with clinical signs of acute abdomen, which can mimic appendicitis, diverticulitis, ulcer peptic disease, and other common inflammatory conditions. Besides, patients commonly do not refer that a fish bone was swallowed. Since this condition is usually not suspected by referring physicians of the emergency department (ED), radiologists play a key role in this diagnosis; the spectrum of these imaging features must be known in order to be accurately reported in the ED.

Theranostics in Nuclear Medicine: Emerging and Re-emerging Integrated Imaging and Therapies in the Era of Precision Oncology.

Theranostics refers to the pairing of diagnostic biomarkers with therapeutic agents that share a specific target in diseased cells or tissues. Nuclear medicine, particularly with regard to applications in oncology, is currently one of the greatest components of the theranostic concept in clinical and research scenarios. Theranostics in nuclear medicine, or nuclear theranostics, refers to the use of radioactive compounds to image biologic phenomena by means of expression of specific disease targets such as cell surface receptors or membrane transporters, and then to use specifically designed agents to deliver ionizing radiation to the tissues that express these targets. The nuclear theranostic approach has sparked increasing interest and gained importance in parallel to the growth in molecular imaging and personalized medicine, helping to provide customized management for various diseases; improving patient selection, prediction of response and toxicity, and determination of prognosis; and avoiding futile and costly diagnostic examinations and treatment of many diseases. The authors provide an overview of theranostic approaches in nuclear medicine, starting with a review of the main concepts and unique features of nuclear theranostics and aided by a retrospective discussion of the progress of theranostic agents since early applications, with illustrative cases emphasizing the imaging features. Advanced concepts regarding the role of fluorine 18-fluorodeoxyglucose PET in theranostics, as well as developments in and future directions of theranostics, are discussed. ©RSNA, 2020 See discussion on this article by Greenspan and Jadvar.

Prostate-specific Membrane Antigen PET: Therapy Response Assessment in Metastatic Prostate Cancer.

Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic PC has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification.© RSNA, 2020See discussion on this article by Barwick and Castellucci.

Revisiting Prostate Cancer Recurrence with PSMA PET: Atlas of Typical and Atypical Patterns of Spread.

The introduction of prostate-specific membrane antigen (PSMA) in clinical practice has revolutionized evaluation of biochemical recurrence of prostate cancer after curative-intent treatment. The high expression of this glycoprotein in prostate cancer cells makes PSMA imaging superior to the current conventional staging methods, namely bone scanning and CT. The high capability of PSMA imaging for identifying very small previously undetected lesions has been widely demonstrated in the literature, leading to a rethinking of patient management by oncologists, urologists, and radiation oncologists. The typical and predictable patterns of spread in prostate cancer are still more prevalent, such as spread to pelvic lymph nodes and bone metastasis, but different patterns of disease spread are becoming more commonly recognized with higher reliability because PSMA imaging allows detection of more typical and atypical lesions than conventional imaging. Furthermore, it is important for the reading physician to recognize and understand the typical disease spread and the most prevalent atypical prostate cancer relapses, not only to heighten the relevancy of reports but also to improve imaging consultancy in multispecialty oncologic practice. ©RSNA, 2019.

Exercise-induced muscle vasodilatation and treadmill exercise test responses in individuals without overt heart disease.

BACKGROUND: The beneficial effects of exercise on cardiovascular health may be related to the improvement in several physiologic pathways, including peripheral vascular function. The aim of this study was to evaluate the relationship between cardiovascular responses during the treadmill exercise test and exercise-induced muscle vasodilatation in individuals without overt heart disease. METHODS: The study included 796 asymptomatic subjects (431 females and 365 males) without overt heart disease. We evaluated the heart rate (chronotropic reserve and heart rate recovery), blood pressure (maximum systolic and diastolic blood pressure as well as systolic blood pressure recovery) and exercise capacity during symptom-limited treadmill exercise testing. Exercise-induced muscle vasodilatation was studied with venous occlusion plethysmography and estimated by forearm blood flow and vascular conductance responses during a 3-min handgrip maneuver. RESULTS: Forearm blood flow increase during the handgrip exercise was positively associated with heart rate recovery during treadmill exercise testing (p < 0.001). Forearm vascular conductance increase during the handgrip exercise was inversely associated with exercise diastolic blood pressure during exercise treadmill testing (p = 0.038). No significant association was found between exercise capacity and exercise-induced muscle vasodilation. CONCLUSION: In a sample of individuals without overt heart disease, exercise-induced muscle vasodilatation was associated with heart rate and blood pressure responses during treadmill exercise testing, but was not associated with exercise capacity. These findings suggest that favorable hemodynamic and chronotropic responses are associated with better vasodilator capacity, but exercise capacity does not predict muscle vasodilatation.

Synthesis and Antiproliferative Evaluation of d-Glucuronamide-Based Nucleosides and (Triazolyl)methyl Amide-Linked Pseudodisaccharide Nucleosides.

The synthesis and antiproliferative evaluation of novel d-glucopyranuronamide-containing nucleosides is described. Based on our previously reported anticancer d-glucuronamide-based nucleosides, new analogues comprising N/O-dodecyl or N-propargyl substituents at the glucuronamide unit and anomerically-N-linked 2-acetamido-6-chloropurine, 6-chloropurine or 4-(6-chloropurinyl)methyl triazole motifs were synthesized in 4-6 steps starting from acetonide-protected glucofuranurono-6,3-lactone. The methodologies were based on the access to N-substituted glycopyranuronamide precursors, namely 1,2-O-acetyl derivatives or glucuronoamidyl azides for further nucleobase N-glycosylation or 1,3-dipolar cycloaddition with N9 - and N7 -propargyl-6-chloropurines, respectively. N-Propargyl glucuronamide-based N9 -purine nucleosides were converted into (triazolyl)methyl amide-6,6-linked pseudodisaccharide nucleosides via cycloaddition with methyl 6-azido-glucopyranoside. A CuI/Amberlyst A-21 catalytic system employed in the cycloaddition reactions also effected conversion into 6-dimethylaminopurine nucleosides. Antiproliferative evaluation in chronic myeloid leukemia (K562) and breast cancer (MCF-7) cells revealed significant effects exhibited by the synthesized monododecylated purine-containing nucleosides. A N-propargyl 3-O-dodecyl glucuronamide derivative comprising a N9 -ß-linked 6-chloropurine moiety was the most active compound against MCF-7 cells (GI50 =11.9 µM) while a related α-(purinyl)methyltriazole nucleoside comprising a N7 -linked 6-chloropurine moiety exhibited the highest activity against K562 cells (GI50 =8.0 µM). Flow cytometry and immunoblotting analysis of apoptosis-related proteins in K562 cells treated with the N-propargyl 3-O-dodecyl glucuronamide-based N9 -linked 6-chloropurine nucleoside indicated that it acts via apoptosis induction.

High-sensitivity C-reactive protein levels and treadmill exercise test responses in men and women without overt heart disease.

BACKGROUND: C-reactive protein (CRP) is a marker of systemic inflammatory activity and may be modulated by physical fitness. Treadmill exercise testing is used to evaluate cardiovascular health through different variables including exercise capacity, heart rate and blood pressure responses. It was hypothesized that CRP levels are associated with these variables in men and women without overt heart disease. METHODS: A total of 584 asymptomatic subjects (317 [54.3%] women and 267 [45.7%] men) were enrolled in the present study and underwent clinical evaluation. CRP levels in men and women were examined relative to clinical characteristics and to variables of treadmill exercise testing: peak heart rate, exercise systolic blood pressure, exercise time, chronotropic reserve and heart rate recovery at the first and second minutes after exercise. Multivariate analysis was performed using a log-linear regression model. RESULTS: In women, exercise time on the treadmill exercise test (P=0.009) and high-density lipoprotein cholesterol levels (P=0.002) were inversely associated with CRP levels. Body mass index (P<0.001) and total cholesterol levels (P=0.005) were positively associated with CRP levels. In men, exercise time on the treadmill exercise test was inversely associated with CRP levels (P=0.015). Body mass index (P=0.001) and leukocyte count (P=0.002) were positively associated with CRP levels. CRP levels were not associated with peak heart rate, chronotropic reserve, heart rate recovery at the first and second minutes, or exercise systolic blood pressure. CONCLUSIONS: These findings contribute to the evidence that CRP is lower in individuals with better exercise capacity and demonstrate that this relationship is also apparent in individuals without overt heart disease undergoing cardiovascular evaluation through the treadmill exercise test. Lowering inflammatory markers may be an additional reason to stimulate sedentary individuals with low exercise capacity in the treadmill exercise test to improve physical conditioning through regular exercise.

New brachypterous species of Dichotomius Hope, with taxonomic notes in the subgenus Luederwaldtinia Martínez (Coleoptera: Scarabaeidae: Scarabaeinae).

An overview of the subgenus Dichotomius (Luederwaldtnia) and its species groups is presented with species groups proposed and a provisional identification key provided. Dichotomius (Luederwaldtnia) vidaurrei, a brachypterous new species from Bolivia, is described. Another brachypterous species, from Brazil, D. mysticus (Luederwaldt) is redescribed. Dichotomius paraguayanus Gandini & Aguilar is synonymized with Canthidium kelleri (Martínez, Halffter & Pereira). Some aspects of the evolution of flightlessness in Dichotomius are discussed.

The value of PET/CT for cytoreductive surgery selection in recurrent ovarian carcinoma.

OBJECTIVE: To evaluate the value of positron emission tomography/computed tomography (PET/CT) in predicting no residual disease (NRD) after secondary cytoreductive surgery (SCS) compared with MSK criteria, the iMODEL, and the AGO score. METHODS: We analyzed 112 patients with platinum-sensitive ovarian carcinoma who underwent SCS. We excluded patients for whom PET/CT was not performed, those without sufficient data, and who received chemotherapy before SCS. Ultimately, 69 patients were included. RESULTS: Variables that correlated with NRD were peritoneal carcinomatosis index (odds ratio [OR]=0.91; 95% confidence interval [CI]=0.83-0.99; p=0.044), European Cooperative Oncology Group Performance Status (ECOG) 0 (OR=8.0; 95% CI=1.34-47.5; p=0.022), and ≤2 lesions by PET/CT (OR=4.36; 95% CI=1.07-17.7; p=0.039). Of the patients with ≤2 lesions by PET/CT, 48 (92.3%) underwent complete SCS. The sensitivity, positive predictive value, negative predictive value, and accuracy of PET/CT for NRD were 85.7%, 92.3%, 33.3%, and 81.2%, respectively. NRD was achieved after fulfilling the MSK criteria, iMODEL and AGO Score in 89.1%, 88.1% and 85.9%, respectively. The accuracy of the MSK criteria, iMODEL, and AGO score in predicting NRD was 87%, 83.3%, and 77.3%, respectively. The PET/CT findings agreed well with the AGO score and iMODEL. The addition of PET/CT to these models increased the NRD rates (92.2%, 91.8%, and 89.4% for MSK+PET/CT, iMODEL+PET/CT, and AGO+PET/CT, respectively), but lowered their accuracy. CONCLUSION: We observed NRD in 92.3% of patients with ≤2 lesions by PET/CT, with an accuracy of 81.2%. PET/CT did not increase the accuracy of the MSK criteria, iMODEL, or AGO score models.

Digital Image Correlation for Measuring Full-Field Residual Stresses in Wire and Arc Additive Manufactured Components.

This study aims to demonstrate the capability of the digital image correlation (DIC) technique for evaluating full-field residual stresses in wire and arc additive manufactured (WAAM) components. Investigations were carried out on WAAM steel parts (wall deposited on a substrate) with two different wall heights: 24 mm and 48 mm. Mild steel solid wire AWS ER70S-6 was used to print WAAM walls on substrates that were rigidly clamped to H-profiles. DIC was used to monitor the bending deformation of WAAM parts during unclamping from the H-profiles, and residual stresses were calculated from the strain field captured during unclamping. Residual stresses determined from the proposed DIC-based method were verified with an analytical model and validated by the results from established residual stress measurement techniques, i.e., the contour method and X-ray diffraction.

Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib, or nilotinib: A cohort study using data from a large multinational collaborative network.

Background: Breakpoint cluster region-Abelson gene (BCR-ABL) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs. Objectives: This study aims to compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) < 50%, and venous thromboembolic events (VTE) in patients with CML treated with BCR-ABL TKIs, using data from a large multinational network. Methods: Patients aged ≥ 18 years with CML treated with imatinib, dasatinib, or nilotinib without prior cardiovascular or cerebrovascular disease were included. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated. Results: We identified 3,722 patients with CML under treatment with imatinib (n = 1,906), dasatinib (n = 1,269), and nilotinib (n = 547). Patients with imatinib compared to dasatinib showed a higher hazard ratio (HR) for ACE (HR 2,13, 95% CI 1.15-3.94, p = 0.016). Patients with imatinib presented a lower HR than nilotinib for ACE (HR 0.50, 95% CI 0.30-0.83, p = 0.0074). In relation to heart failure or LVEF < 50%, patients with imatinib had a higher HR than dasatinib (HR 9.41, 95% CI 1.22-72.17, p = 0.03), but no significant difference was observed between imatinib and nilotinib (HR 0.48, 95% CI 0.215-1.01, p = 0.064). Conclusion: In this retrospective study with a large number of patients with CML, those treated with nilotinib had a higher 5-year ratio of ACE, while patients with dasatinib showed a lower ratio than patients with imatinib. The ratio of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.