ABSTRACT
Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.
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In the recent decades, remarkable successes have been recorded in the treatment of Hodgkin's lymphoma to the point that today it represents one of the neoplasms with the highest rates of cure and with the highest life expectancy. Nonetheless, this raises the concern for the health of long- term survivors. Late side effects of treatments in synergy with other risk factors expose survivors to increased morbidity and impaired quality of life. In the complexity of the topics concerning these last aspects, an area of growing interest is that of bone damage that follows Hodgkin Lymphoma and its treatments. In this narrative review, we conducted our work through assessment of available evidence focusing on several aspects linking bone damage and quality of life with Hodgkin lymphoma and its treatments. At present, the problem of osteopenia and osteoporosis in Hodgkin lymphoma survivors is a theme for which awareness and knowledge need to be implemented.
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The goal of therapy in essential thrombocythemia (ET) is reducing thrombotic risk. No algorithm to predict hemorrhage risk exists. The impact ofanti-platelet, cytoreductive and anticoagulation therapies on risk of major bleeding (MB) was evaluated. MB events were retrospectively analyzed in 1381 ET from 10 European centers. There were 0.286 MB events/person-year. Neither the International Thrombosis Prognostic Score for thrombosis in essential thrombocythemia (IPSET-t) nor the revised IPSET-t (r-IPSET-t) was predictive for hemorrhage-free survival at 10 years (p = 0.092 vs p = 0.1). Ageand leukocyte count were MB risk factors, while low hemoglobin was protective. For ET with extreme thrombocytosis (ExtT) and leukocytosis cytoreduction was not protective. MB were more frequent in ET with ExtT who received anticoagulation. Antiplatelet therapy was not, while anticoagulation was a risk factor for MB (HR 3.05, p = 0.016, CI 1.23-7.56), in particular vitamin K antagonists (22.6% of those treated had a MB event, HR 2.96, p = 0.004, CI 1.41-6.22). Survival at 10 years was associated with hemorrhage (OR 2.54, p < 0.001) but not thrombosis (HR 0.95, p = 0.829). Hemorrhage has a higher risk of mortality than thrombosis. Improved risk stratification for MB is necessary. The choice of anticoagulation, cytoreduction and antiplatelet therapies is an important area of research in ET.
Subject(s)
Thrombocythemia, Essential , Thrombocytosis , Thrombosis , Humans , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/drug therapy , Retrospective Studies , Prognosis , Thrombosis/etiology , Hemorrhage/etiology , Risk Factors , Anticoagulants/adverse effects , Thrombocytosis/etiologyABSTRACT
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis (NMDARe) is the most common cause of nonviral encephalitis, mostly affecting young women and adolescents with a strong female predominance (F/M ratio of around 4:1). NMDARe is characterized by the presence of cerebrospinal fluid (CSF) antibodies against NMDARs, even though its pathophysiological mechanisms have not totally been clarified. The clinical phenotype of NMDARe is composed of both severe neurological and neuropsychiatric symptoms, including generalized seizures with desaturations, behavioral abnormalities, and movement disorders. NMDARe is often a paraneoplastic illness, mainly due to the common presence of concomitant ovarian teratomas in young women. Abdominal ultrasonography (US) is a key imaging technique that should always be performed in suspected patients. The timely use of abdominal US and the peculiar radiological features observed in NMDARe may allow for a quick diagnosis and a good prognosis, with rapid improvement after the resection of the tumor and the correct drug therapy.
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Background and Objectives. Acute aortic syndromes (AASs) are emergencies burdened by high morbidity and mortality. Guideline-recommended diagnostic workup is based on pre-test probability assessment (PPA) and d-dimer testing. However, the performance of PPA and d-dimer has never been studied in individuals with previous AAS (pAAS), which represent a challenging population. Materials and Methods. We analyzed a registry of patients with pAAS evaluated in two Emergency Departments (EDs) for suspected novel AAS (nAAS). Enrolment criteria were history of pAAS and the presence of truncal pain, syncope or perfusion deficit. All patients underwent advanced imaging. Clinical data were registered prospectively and PPA was performed by applying the aortic dissection detection (ADD) and an aorta simplified (AORTAs) score. Results. A total of 128 patients were enrolled, including 77 patients with previous Stanford type A aortic dissection and 45 patients with previous Stanford type B aortic dissection. The final diagnosis was nAAS in 40 (31%) patients. Clinical variables associated with nAAS were: aortic valve disease, thoracic aortic aneurysm, severe pain, sudden pain, ripping/tearing pain and hypotension/shock. ADD score ≥ 2 had a sensitivity of 65% and a specificity of 83% for nAAS; AORTAs score ≥ 2 had a sensitivity of 48% and a specificity of 88%. d-dimer (cutoff ≥ 500 ng/mL or age-adjusted cutoff) had a sensitivity of 97% and a specificity of 13%/14.7%, for diagnosis of nAAS. Patients that were candidates for guideline-compliant PPA/d-dimer integrated rule-out were: 5 (4.9%) with ADD ≤ 1/d-dimer and 8 (7.8%) with AORTAs ≤ 1/d-dimer < age-adjusted cutoff. None of them had a nAAS. Conclusions. Patients with pAAS evaluated in the ED for red-flag symptoms showed intermediate-to-high pre-test probability of nAAS. The ADD score had lower sensitivity and specificity than in unselected patients. d-dimer, alone and integrated with PPA, was highly sensitive for nAAS, but very unspecific. PPA/d-dimer integrated strategies are unlikely to significantly reduce the number of patients with pAAS undergoing advanced imaging.
Subject(s)
Acute Aortic Syndrome , Aortic Dissection , Humans , Aortic Dissection/diagnosis , Probability , Pain , BiomarkersABSTRACT
INTRODUCTION: Blunt thoracic trauma (BTT) is a leading cause of emergency department (ED) trauma-related attendance. Risk prediction tools are commonly to predict patients' outcomes and assign them to the most appropriate care setting. The STUMBL score is a prognostic model for BTT, derived and validated in the United Kingdom; items comprising the score are age, number of rib fractures, use of pre-injury anticoagulants, chronic lung disease and oxygen saturation levels. This study's aim was to validate the STUMBL score in an Italian ED. METHODS: This single-centre retrospective validation study was conducted in the ED of Santa Croce and Carle hub hospital in Cuneo, north-western Italy. All patients with an ED attendance for isolated BTT from 2018 to 2021 were included. Exclusion criteria were an age of under eighteen and the presence of any immediately life-threatening lesion. The primary outcome was the development of trauma-related complications, defined by the occurrence of one or more of the following: in-hospital mortality, pulmonary complications (infection, pleural effusion, haemothorax, pneumothorax, pleural empyema), need for intensive care unit admission, hospital length of stay equal to or greater than seven days. The performance of the STUMBL score was analysed in terms of discrimination with the evaluation of the receiver operating characteristic curve and calibration with the Hosmer-Lemeshow test and with the calibration belt. RESULTS: 745 patients were enroled (median age 64 [25th;75th percentile: 50;78], male/female ratio 1:4, median Charlson comorbidity index 2 [1;4], median STUMBL score 11 [6;17]). 65.2% of patients were discharged home after ED evaluation. 203 patients (27.2%) developed the primary outcome. The STUMBL score was significantly different in patients with complications compared to those without complications (9 [5;13] vs 21 [17;25], p < 0.001). The C index of the score for the primary outcome was 0.90 (95% CI 0.88-0.93), and the result of the Hosmer-Lemeshow test was 9.01 (p = 0.34). STUMBL score = 16 has a sensitivity of 0.80 (95% CI 0.75-0.85), specificity of 0.87 (95% CI 0.84-0.90), a positive predictive value of 0.70 (95% CI 0.64-0.76), and a negative predictive value of 0.92 (95% CI 0.90-0.94). CONCLUSION: In this validation study, the STUMBL score demonstrated excellent discrimination and calibration in predicting the outcome of patients attending the ED with a BTT.
Subject(s)
Emergency Service, Hospital , Wounds, Nonpenetrating , Humans , Male , Female , Middle Aged , Retrospective Studies , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/therapy , Prognosis , Hospitalization , ROC CurveABSTRACT
Essential thrombocythemia, as defined by the WHO in 2016, is a Philadelphia-negative chronic myeloproliferative neoplasm showing a better prognosis than polycythemia vera and myelofibrosis. In a variable percentage, patients with essential thrombocythemia show none of the known driver-gene mutations that may occur on JAK2, CALR, and MPL genes. Such patients are classified as triple-negative and their clinical features and prognosis have not been described with precision yet. In this study, we evaluated some of the characteristics of this population by comparing them with those of patients with driver-gene mutated ET. Data from 266 consecutive essential thrombocythemia patients were analysed. Triple-negative patients had a significantly lower symptom load and a lower frequency of splenomegaly at diagnosis. The results show that the rate of thrombosis was equal in the two subgroups. Overall survival was slightly better in the triple-negative group of patients.
ABSTRACT
Thrombosis and haemorrhage are frequent in patients with essential thrombocythaemia (ET). The 2016 revised International Prognostic Score for Thrombosis in Essential Thrombocythaemia-thrombosis (r-IPSET-t) score stratifies patients into very-low- (VLR), low- (LR), intermediate- (IR) and high-risk (HR) groups. We validated the r-IPSET-t in the biggest population of patients with ET (n = 1381) to date and found it to be a better fit than the earlier IPSET-t score. With an average follow-up of 87.7 months, there were 0.578 thrombotic events/person-year and 0.286 bleeding events/person-year after diagnosis. The 10-year thrombosis-free survival was 88% and 99% for the r-IPSET-t LR and VLR groups (p < 0.001). Cytoreduction was a thrombotic risk factor in younger patients (aged <60 years, hazard ratio 9.49, p = 0.026; aged ≥60 years, hazard ratio 1.04, p = 0.93). In multivariable Cox regression analysis, anti-aggregation after diagnosis was protective for thrombosis (hazard ratio 0.31, p = 0.005) but a risk factor for major bleeding (hazard ratio 10.56, p = 0.021). Of the IPSET-t HR and LR groups, 132/780 and 249/301 were re-classified as LR and VLR respectively (p < 0.001). The European LeukemiaNET (ELN) does not recommend aspirin for VLR patients but in this real-life analysis 83.1% of VLR patients received it. Our results validate the r-IPSET-t score as more predictive for thrombosis than the ELN-recommended IPSET-t and raise concerns about unnecessary cytoreductive and anti-aggregative therapy.
Subject(s)
Thrombocythemia, Essential , Thrombosis , Aspirin/therapeutic use , Humans , Prognosis , Retrospective Studies , Risk Factors , Thrombocythemia, Essential/diagnosis , Thrombosis/diagnosis , Thrombosis/epidemiology , Thrombosis/etiologyABSTRACT
The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors and/or immunomodulatory drugs +/- the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis of 27 phase 2/3 randomized trials including a total of 12,935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric used to build a ranking chart. With a mean SUCRA of 83.8 and 80.08 respectively, VMP + Daratumumab (DrVMP) and Rd + Daratumumab (DrRd) reached the top of the chart. However, SUCRA is designed to work for single outcomes. To overcome this limitation, we undertook a dimensionality reduction approach through a principal component analysis, that unbiasedly grouped the 23 regimens into three different subgroups. On the bases of our results, we demonstrated that first line treatment for NEMM should be based on DrRd (most active, but continuous treatment), DrVMP (quite "fixed-time" treatment), or, alternatively, VRD and that, surprisingly, melphalan as well as Rd doublets still deserve a role in this setting.
Subject(s)
Multiple Myeloma , Humans , Network Meta-Analysis , Multiple Myeloma/drug therapy , Randomized Controlled Trials as TopicABSTRACT
Assessment of host-related factors is a crucial aspect in the comprehensive management of cancer patients. A distinct nutritional disturbance linked to cancer has been recognized to be associated with negative outcomes. However, compared to solid tumors, only a limited number of studies have looked specifically at nutritional issues in the field of lymphoma. The aim of this review is to integrate the current knowledge on interactions between malnutrition and lymphoma and address most relevant and pertinent questions. We first provide a literature review on the mutual biological relationship between malnutrition and lymphoma. Next, we explore the overlap between malnutrition, sarcopenia, cachexia and frailty in lymphoma studies. In addition, we summarize the clinical assessment scales used to measure malnutrition in lymphoma subjects. Furthermore, we address the problem of nutritional interventions aimed at patients who are candidates for treatment for lymphoma. Malnutrition can arise as a consequence of lymphoma disease and can in turn promote lymphomagenesis, negatively affect the response to therapy and favor adverse event to treatment. There is increasing evidence that malnutrition, sarcopenia and cachexia in lymphoma are intimately inter-related and are a hallmark of frailty. A variety of different tools are recorded with the apparent ability to describe nutritional status and to impact prognosis in lymphoma patients. Finally, a network of prognostic host- and disease-related factors is proposed where malnutrition can interact with each other in complex ways.
Subject(s)
Frailty , Lymphoma, Non-Hodgkin , Malnutrition , Neoplasms , Sarcopenia , Cachexia/complications , Frailty/complications , Humans , Lymphoma, Non-Hodgkin/complications , Lymphoma, Non-Hodgkin/therapy , Malnutrition/complications , Neoplasms/complications , Sarcopenia/complicationsABSTRACT
B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.
Subject(s)
Lymphoma, B-Cell , Lymphoma , Lymphoproliferative Disorders , Humans , Immune System/pathology , Immunotherapy, Adoptive , Lymphoma/drug therapy , Lymphoma, B-Cell/therapy , Lymphoproliferative Disorders/pathology , Tumor MicroenvironmentABSTRACT
AIMS: Tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukaemia (CML) can cause cardiovascular adverse events. So far, the Systematic Coronary Risk Evaluation (SCORE) charts of the European Society of Cardiology (ESC) have been used to identify cancer patients at increased cardiovascular risk. The primary aim of our study was to evaluate the usefulness of the new cardiovascular risk assessment model proposed by the Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the ESC in collaboration with the International Cardio-Oncology Society (ICOS) to stratify the cardiovascular risk in CML patients, compared with SCORE risk charts. The secondary aim was to establish the incidence of adverse arterial events (AEs) in patients with CML treated with TKIs and the influence of preventive treatment with aspirin. METHODS AND RESULTS: A retrospective single-centre observational study was carried out on 58 patients (32 men and 26 women; mean age ± SD: 59 ± 15 years) with CML treated with TKIs for a median period of 43 ± 31 months. Cardiological evaluation was performed and cardiovascular risk was estimated with SCORE risk charts and with the new risk assessment tool proposed by HFA/ICOS. AEs were recorded. According to SCORE charts and the new HFA/ICOS risk stratification tool, respectively, 46% (Group A1) and 60% (Group A2) of patients were at high-very high risk, and 54% (Group B1) and 40% (Group B2) at low-moderate risk. AEs were significantly more frequent in Group A1 than Group B1 (P value < 0.01) when considered overall; they were significantly more frequent in Group A2 than Group B2 either overall or considered individually. HFA/ICOS risk stratification tool was significantly more sensitive than SCORE (P < 0.01) in identifying patients at higher risk of cardiovascular toxicity. In addition, we did not find AEs in patients pretreated with aspirin. CONCLUSIONS: The new HFA/ICOS risk stratification model allows a more tailored cardiovascular risk stratification in patients with CML and it is more sensitive than SCORE charts.
Subject(s)
Heart Failure , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Adult , Aged , Aspirin , Cardiotoxicity/etiology , Chronic Disease , Female , Heart Failure/complications , Heart Failure/epidemiology , Humans , Inducible T-Cell Co-Stimulator Protein , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Retrospective Studies , Risk AssessmentABSTRACT
Rarely essential thrombocythemia (ET) is diagnosed in more than one person within a family. Familial myeloproliferative neoplasms are underdiagnosed. In this report, we describe 6 couples of familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation.
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BACKGROUND: Transarterial chemoembolization is the most widely used palliative treatment for unresectable hepatocellular carcinoma; however, arterioportal shunt represents a contraindication to this treatment. OBJECTIVE: The study aims to assess the feasibility of balloon-occluded radiofrequency ablation in the transitory resolution of an extensive arterioportal shunt in patients with advanced hepatocellular carcinoma as a bridge to safe and effective transarterial chemoembolization. METHODS: 12 consecutive patients advanced multinodular unilobar unresectable hepatocellular carcinoma with a target lesion larger than 5 cm (mean diameter 7.7 ± 1.4 cm), not suitable to transarterial chemoembolization due to extensive arterioportal shunt, were recruited. Balloon-occluded radiofrequency ablation of the hepatic area surrounding the shunt during occlusion of the artery supplying the shunt was performed, followed by lobar conventional chemoembolization. Intra/periprocedural complications were evaluated. Technical success was defined by the result of radiofrequency ablation in terms of immediate disappearance, reduction, or persistence of the shunt. Local efficacy of chemoembolization was evaluated at 1-month computed tomography according to m-RECIST criteria. RESULTS: Technical success was achieved in all patients. No major complications were observed. 1- month follow-up showed a mean necrotic diameter of 6.3 cm (range: 3.8-8.7 cm), with an acceptable procedural result and persistence of the shunt. An overall response rate was obtained in all patients, with 25% complete response and 75% partial response. CONCLUSION: Balloon-occluded radiofrequency ablation of an arterioportal shunt in patients with advanced hepatocellular carcinoma can temporarily reduce shunting, allowing to perform safe and therapeutically useful chemoembolization, with satisfactory control of tumor growth.
Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Radiofrequency Ablation , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Combined Modality Therapy , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Radiopharmaceuticals , Retrospective Studies , Treatment OutcomeABSTRACT
Myeloproliferative neoplasms (MPN) are traditionally regarded as a disease of older adults, though a not negligible fraction of cases occurs at a younger age, including women of childbearing potential. MPN in younger patients, indeed, offer several challenges for the clinical hematologist, that goes from difficulties in reaching a timely and accurate diagnosis to a peculiar thrombotic risk, with a relatively high incidence of thromboses in unusual sites (as the splanchnic veins or the cerebral ones). Moreover, the issue of pregnancy is recently gaining more attention as maternal age is rising and molecular screening are widely implemented, leading to a better recognition of these cases, both before and during pregnancy. In the present work we aim at discussing four clinical topic that we identified as areas of uncertainty or true unmet medical needs in the management of younger patients with MPN, with a particular focus on the topic of pregnancy. For each of these topics, we critically reviewed the available evidence that support treatment decisions, though acknowledging that recommendations in this field are mostly based on expert opinion or derived from guidelines of other clinical conditions that share with MPN a high vascular risk, as antiphospholipid syndrome. Taking into consideration both the lack of evidence-based data and the clinical heterogeneity of MPN, we support an individualized strategy of counseling and management for both young patients and for expectant mother with MPN.
Subject(s)
Myeloproliferative Disorders , Neoplasms , Thrombosis , Aged , Female , Humans , Incidence , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/epidemiology , Myeloproliferative Disorders/genetics , Philadelphia Chromosome , PregnancyABSTRACT
ROMEI, a prospective, observational study in patients with myelofibrosis receiving the oral JAK1/2 inhibitor ruxolitinib in real-world practice, assesses treatment adherence based on the 8-item Morisky Medication Adherence Scale (MMAS-8). Here, we present MMAS-8 results at week 24. Overall, 101 of 188 evaluable patients completed the questionnaire at every visit (full completers). Mean (±standard deviation) total MMAS-8 scores remained stable from week 4 to week 24 in the overall population (7.54 ± 0.77 and 7.67 ± 0.70, respectively) and full completers (7.53 ± 0.79 and 7.67 ± 0.73, respectively). Rates of low (MMAS-8 Ë6) or medium (MMAS-8 ≥ 6 to Ë8) adherence were 25-40% and 26-36%, respectively. Fifty-five full completers (54%) reported ≥1 change in adherence category (improvement and/or worsening), most of which were associated with unintentional behavior. The data suggest that one-third of patients receiving ruxolitinib may be undertreated due to non-adherence, potentially undermining disease control, and indicate a need for better interventions addressing noncompliance to oral therapies.
Subject(s)
Janus Kinase 1 , Janus Kinase 2 , Primary Myelofibrosis , Pyrazoles , Pyrimidines , Cohort Studies , Humans , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Medication Adherence , Nitriles/therapeutic use , Primary Myelofibrosis/drug therapy , Prospective Studies , Psychometrics/methods , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Surveys and QuestionnairesABSTRACT
BACKGROUND: Poison frogs are known for the outstanding diversity of alkaloid-based chemical defences with promising therapeutic applications. However, current knowledge about chemical defences in Dendrobatoidea superfamily has two sources of bias. First, cryptic, brown-colored species have been neglected in comparison to those conspicuously colored, and second, there has been little interest in characterizing metabolites other than alkaloids mediating defensive functions. In an effort to contribute to fill the gap of knowledge about cryptic species and broadening the spectrum of compounds analyzed we have applied head-space solid phase microextraction coupled to gas chromatography and mass spectrometry (HS-SPME/GC-MS) for extracting amphibian alkaloids and volatile organic compounds (VOCs) from Silverstoneia punctiventris. RESULTS: Using the skin from 8 specimens in 4 biological replicates we have found 33 different compounds. Twenty of them were classified as VOCs into 15 chemical classes including alkanes, alcohols, carbonyl compounds, methylpyridines, benzothiazoles, N-alkylpyrrolidines, pyrazines, and sesquiterpenoids, some of which were previously reported as repellents, defence compounds or defence pheromones in other organisms, and as sex pheromones in a treefrog. Interestingly, six of the remaining compounds were identified as alkaloids previously reported in other toxic/unpalatable dendrobatid frogs. CONCLUSIONS: This is the first report of alkaloids and VOCs found in the Silverstoneia genus, which has been assumed for decades as non-chemically defended. This study establishes HS-SPME/GC-MS as a new application for a simultaneous approach to amphibian alkaloids and VOCs in poison frogs while opens up new research questions to assess the co-occurrence of both type of compounds and to investigate the evolutionary significance of a defence gradient that includes olfactory avoidance, unpalatability, and toxicity in dendrobatids. In addition, our results show that amphibian alkaloids could have a dual function (olfactory at distance, taste by contact) never explored before neither in Silverstonaeia nor in any other dendrobatid species.
ABSTRACT
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo which cardiology test or exam? Is there an accurate way to estimate the risk that each TKI may determine a cardiovascular adverse event in a CML patient? In a few words, how can we optimize the cardiovascular risk management in CML patients before and during TKI treatment? The aim of this review is to describe cardiac and vascular toxicity of TKIs used for CML treatment according to the most recent literature and to identify unmet clinical needs in cardiovascular risk management and complications in these patients. Regarding the TKI-induced cardiovascular toxicity, the full mechanism is still unclear, but it is accepted that different factors may play different roles: endothelial damage and atherosclerosis, metabolic impairment, hypertensive effect, glomerular impairment, and mast-cell disruption. Preventive strategies are aimed at minimizing cardiovascular risk when CML is diagnosed. Cardio-oncology units in specialized hematology centers may afford a personalized and multidisciplinary approach to the patient, optimizing the balance between treatment of the neoplasm and management of cardiovascular risk.