TARGET: a survey of real-world management of chronic myeloid leukaemia across 33 countries

Despite the availability of guidelines for the management of chronic myeloid leukaemia (CML), various issues may prevent their successful implementation. The TARGET survey examined real-world management of CML patients compared with international recommendations. This online survey was completed in 2017. Results were discussed by a Steering Committee (SC) of eight international haematologists, challenges were identified and practical solutions developed. Of the 1008 haematologists invited (33 countries), 614 completed the survey. Gaps regarding treatment efficacy and molecular monitoring were identified. Half of the physicians did not perform three-monthly testing of during the initial 12 months of treatment, citing cost as the major barrier, although they know it should be done. Treatment-free remission was not considered a primary treatment goal or as a priority factor influencing treatment decisions. European Leukemia Net guidelines interpretation was generally acceptable, but awareness regarding management of persistent adverse events was poor. Practical solutions proposed by the SC were mostly focused on enhancing physician education and awareness, or encouraging hospitals to work with the government, in order to improve the quality of BCR-ABL testing. Gaps in current CML management were identified compared with international recommendations, which the proposed practical solutions would help to address.     

Impact of puberty on the evolution of cerebral perfusion during adolescence

Puberty is the defining biological process of adolescent development, yet its effects on fundamental properties of brain physiology such as cerebral blood flow (CBF) have never been investigated. Capitalizing on a sample of 922 youths ages 8–22 y imaged using arterial spin labeled MRI as part of the Philadelphia Neurodevelopmental Cohort, we studied normative developmental differences in cerebral perfusion in males and females, as well as specific associations between puberty and CBF. Males and females had conspicuously divergent nonlinear trajectories in CBF evolution with development as modeled by penalized splines. Seventeen brain regions, including hubs of the executive and default mode networks, showed a robust nonlinear age-by-sex interaction that surpassed Bonferroni correction. Notably, within these regions the decline in CBF was similar between males and females in early puberty and only diverged in midpuberty, with CBF actually increasing in females. Taken together, these results delineate sex-specific growth curves for CBF during youth and for the first time to our knowledge link such differential patterns of development to the effects of puberty.Blood perfusion is one of the fundamental physiologic properties of any organ and is of particular relevance for the human brain, which receives 15% of cardiac output despite only representing 2% of body mass (1). Prior work has shown that cerebral blood flow (CBF) declines markedly throughout childhood and adolescence (2–4). Along with gray matter loss and white matter expansion (5), CBF thus represents one of the most important properties of brain physiology that changes during youth and may be critical for establishing normative growth charts of brain development. CBF is coupled to regional metabolism (6, 7), changes under cognitive demands (8), responds specifically to psychoactive drugs (9), and is abnormal in a variety of psychiatric conditions including schizophrenia (10) and addiction (11). Thus, characterization of normative trajectories of CBF during adolescent development is highly relevant for understanding both normal brain function and its aberrations in psychopathology.Growth curves of height, weight, and head circumference used in typical pediatric practice are separated by sex, because the timing and tempo of growth are different among males and females. One reason for this is the influence of puberty, which is the defining biological process of adolescence. Puberty results in divergent, sex-specific maturation that is driven by the influence of steroid and other metabolic hormones including estrogen and testosterone. Prior work has demonstrated sex differences in patterns of structural brain development (5, 12), and a growing body of literature has begun to establish the influence of puberty on this process (13, 14).In contrast to research on structural brain development, work on cerebral perfusion during development has thus far been relatively sparse. Early research by Kennedy and Sokoloff (15), using a modified Kety–Schmidt nitrous oxide method (16), established that whole-brain CBF was 106 mL⋅100 g⁻¹⋅min⁻¹ in children, compared with 60 mL⋅100 g⁻¹⋅min⁻¹ in adults. Later, CBF was measured on a regional basis using techniques such as ¹³³Xe clearance or ¹⁵O PET. However, sample sizes of these studies were limited by the need for ionizing radiation exposure, which is particularly problematic in pediatric populations. Nonetheless, these studies reliably demonstrated that CBF is elevated during childhood then declines throughout adolescence (3, 17, 18). In adulthood, females have higher CBF than males (8, 19). However, prior nuclear imaging studies in youth were too small (typically n = 20–40) to characterize sex differences during development.Arterial spin labeling (ASL) using MRI permits noninvasive quantification of cerebral perfusion without the use of ionizing radiation (20, 21) but gives comparable gray matter CBF measurements when validated versus PET (22, 23). This feature provides a critical advantage for applications in pediatric populations (4), allowing for a substantial increase in sample size. Using ASL, Taki et al. (24, 25) replicated prior findings of declining perfusion in adolescence and also reported that females had higher perfusion in the posterior cingulate cortex (pCC), owing to a steeper rate of CBF decline in males. However, it is not known whether such effects are limited only to the pCC or whether developmental trajectories of perfusion differ between males and females in other regions, potentially in a complex nonlinear fashion. Divergent trajectories in multiple regions are to be expected, because adult females have higher CBF than males across brain regions beyond the pCC (8, 19, 26, 27). However, it is not yet known when such differences emerge in development.Importantly, no study has investigated whether emerging sex differences in cerebral perfusion seen in adolescence are due to the differential impact of puberty. Studies from both animals and humans provide good reason to suspect that puberty may play a key role in CBF sex differences: Estrogens increase CBF in both animals and humans and also may promote neurogenesis and axonal sprouting (28–31). However, because the progression of age and puberty are correlated, large samples are required to systematically parse the relative influence of each. Here, we investigated developmental patterns of cerebral perfusion in males and females using ASL data from the Philadelphia Neurodevelopmental Cohort (PNC) (32), which constitutes the largest sample of cerebral perfusion yet reported. We hypothesized that differences in cerebral perfusion between males and females would relate to the impact of puberty. As described below, we found pronounced evidence for differential patterns of developmental perfusion in males and females, driven in part by the effects of puberty.     

Ruxolitinib induces autophagy in chronic myeloid leukemia cells

Tumor Biology - Ruxolitinib is the first agent used in myelofibrosis treatment with its potent JAK2 inhibitory effect. In this novel study, we aimed to discover the anti-leukemic effect of...     

The association of occlusal factors with masticatory muscle tenderness in 10- to 19-year old Turkish subjects

The aims of this study were (1) to investigate the relationship between occlusal factors and masticatory muscle tenderness among 10- to 19-year-old (mean 14 years eight months) Turkish subjects and (2) to identify possible sex differences between them. The sample consisted of 716 individuals (355 male and 361 female subjects). Tenderness with palpation of masseter and temporalis muscles and functional manipulation of lateral and medial pterygoid muscles was registered. The examiners recorded the Angle classification bilaterally for molars, presence of anterior and posterior crossbites, excessive overjet, open and deep bites, functional shift, and severity of anterior crowding. Associations between the occlusal factors and muscle tenderness according to sex were evaluated with chi-square analysis. Statistically significant associations were found between masticatory muscle tenderness and all the investigated occlusal factors except posterior crossbite and functional shift. Masseter, medial, and lateral pterygoid muscle tenderness was higher in female subjects. Medial and lateral pterygoid muscle tenderness in Class I cases and masseter and medial pterygoid muscle tenderness in Class II, division 1 malocclusion cases were higher in female subjects (P < .05). In open-bite cases, medial pterygoid muscle tenderness (P < .05), in deep-bite cases, masseter (P < .01) and medial pterygoid (P < .05) muscle tenderness, and in excessive overjet cases, masseter muscle tenderness (P < .05) were also higher in female subjects. These results suggest that greater masticatory muscle tenderness in female subjects may contribute to the greater prevalence of temporomandibular disorders in them.     

Risk factors for poor mobilization in solid tumors: How effectively can we mobilize patients with solid tumors?

Background

In the literature, risk factors for poor mobilization were tried to identify. However, most of the studies consisted heterogeneous group of patients including both hematologic and oncologic malignancies. In this study, we aimed to identify the risk factors for poor mobilization in adults with solid tumors.

Long-term follow-up of iatrogenic atrial septal defect: after percutaneous mitral balloon valvuloplasty

During percutaneous mitral balloon valvuloplasty, the Inoue method leaves patients with an iatrogenic atrial septal defect. In this study, we evaluated the factors affecting the development of iatrogenic atrial septal defect and searched for the possible influence of this defect on long-term outcomes.We reviewed the medical records of 267 patients who had undergone successful percutaneous mitral balloon valvuloplasty for symptomatic moderate or severe mitral stenosis from January 2000 through March 2004. Sixty-three of the 267 patients were enrolled in a face-to-face follow-up study. We noted their clinical and demographic characteristics. All included patients were asked for the endpoints of repeat percutaneous mitral balloon valvuloplasty or mitral valve surgery, cerebrovascular accident or transient ischemic attack, and the need of intervention for the iatrogenic atrial septal defect. They underwent standard 2-dimensional and Doppler echocardiographic examination. The presence of iatrogenic atrial septal defect was evaluated via the color-Doppler technique in the subcostal view and via contrast echocardiography.Patients were subclassified in accordance with the presence (n = 15) or absence (n = 48) of echocardiographically proven persistent iatrogenic atrial septal defect. When we compared the 2 groups, there were no significant differences in baseline demographic characteristics or in pre- and postprocedural echocardiographic data.We conclude that the presence of persistent iatrogenic atrial septal defects might not be predicted from echocardiographic or demographic data in patients undergoing percutaneous mitral balloon valvuloplasty. Fortunately, these defects are small in size and low in shunt ratio. They appear not to be associated with serious long-term outcomes.     

Giant myxoinflammatory fibroblastic sarcoma with bone invasion:a very rare clinical entity and literature review

Myxoinflammatory fibroblastic sarcoma （MIFS） is a rare low-grade, malignant soft tissue tumor that is usually observed in the extremities of adult patients. Magnetic resonance imaging findings for this tumor type have rarely been reported. We report a case involving the distal left femur of a middle-aged man and tumoral invasion of the bone, which, to our knowledge, has been previously described only once. He was treated with distal femoral tumor resection and reconstruction with a modular prosthesis. Histopathologic diagnosis confirmed MIFS. We reviewed literature of the diagnostic imaging and bone invasion findings associated with this tumor type.     

Wall motion velocities of ascending aorta measured by tissue Doppler imaging in obese children

Background: Obesity is associated with the development of early cardiovascular abnormalities such as atherosclerotic lesions. Arterial stiffness may be an indicator of early vascular changes signaling the development of vascular disease. The objective of the current study was to screen aortic elastic properties with tissue Doppler imaging in obese children. Methods: We examined 37 obese children and 30 age‐ and sex‐matched normal subjects. Anthropometric measurements and metabolic risk profile were assessed in a physical examination and with blood taking. The subjects were divided into two subgroups: those with and without metabolic syndrome. Internal aortic systolic and diastolic diameters by M‐mode echocardiography and aortic systolic upper‐wall tissue velocity by tissue Doppler imaging were measured 3 cm above the aortic valve. Aortic distensibility and aortic stiffness index were calculated using accepted formulae. Results: Aortic stiffness parameters and both tissue Doppler peak systolic and diastolic velocities differed significantly in obese children compared to controls. Among the subgroups, children with metabolic syndrome had a lower aortic stiffness index, aortic distensibility and tissue Doppler velocities. However, only peak diastolic velocities significantly differed between obese children without metabolic syndrome and controls. Homeostatic model scores, diastolic blood pressures and pulse pressures were the strongest to correlate with peak diastolic velocity (r=?0.88, P < 0.001, r=?0.62, P= 0.001 and, r= 0.55, P= 0.001, respectively). Conclusions: Tissue Doppler imaging is a feasible and sensitive method to identify aortic stiffness in obese children. Reduced aortic diastolic velocity is the most prominent early vascular change detected in obese children before metabolic syndrome occurs.     

An aneurysmal left circumflex artery-to-right atrium fistula in a patient with ischemic symptoms: accurate diagnosis with dual-source CT angiography

In this report, we present a 55-year-old female patient with a left circumflex artery-to-right atrial fistula associated with a huge saccular aneurysm. She had undergone conventional angiography due to ischemic symptoms. In conventional angiography, a very dilated and tortuous vessel originating from the circumflex artery and continuous with a huge saccular aneurysm was visualized but the drainage site could not be demonstrated. With dual-source CT coronary angiography, the exact anatomy of this fistula was demonstrated and surgery was planned.