Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late first relapse

Gemtuzumab ozogamicin (fGO), a humanized anti‐CD33 monoclonal antibody linked to calicheamicin in combination with intensive chemotherapy gives high response rates in adult acute myeloid leukemia (AML) patients in relapse. However, reduced intensity chemotherapy in combination with fractionated GO has not been tested in aged relapsing patients. Patients from our institution with CD33+ AML aged 55 years or more in first late relapse (≥6 months) were proposed participation in a GO compassionate use program. Induction therapy consisted in fractionated GO (fGO; 3 mg/m², days 1, 4, 7) with standard‐dose cytarabine (200 mg/m²/day, 7 days). Patients were consolidated with two courses of GO and intermediate dose cytarabine. Twenty‐four patients (median age 68 years) received fGO with cytarabine. Median follow‐up was 42 months. The response rate was 75%, including complete remission (CR) in 16 patients and CR with incomplete platelet recovery (CRp) in two patients. Two‐year overall survival (OS) was 51% (95% CI: 28–69) and 2 years relapse‐free survival (RFS) was 51% (95%CI: 25–72). Duration of second CR (CR2) was longer than first CR (CR1) in 9 out of 18 patients. Minimal residual disease (MRD) was negative in evaluable patients in CR2, particularly in NPM1 mutated cases. Toxicity was in line with that of the same fractionated single agent GO schedule. Fractionated GO with low intensity chemotherapy produced high response rates and prolonged CR2 in aged AML patients in first late relapse. Am. J. Hematol. 89:399–403, 2014. © 2013 Wiley Periodicals, Inc.     

Exposure to ambient black carbon derived from a unique inventory and high-resolution model

Black carbon (BC) is increasingly recognized as a significant air pollutant with harmful effects on human health, either in its own right or as a carrier of other chemicals. The adverse impact is of particular concern in those developing regions with high emissions and a growing population density. The results of recent studies indicate that BC emissions could be underestimated by a factor of 2–3 and this is particularly true for the hot-spot Asian region. Here we present a unique inventory at 10-km resolution based on a recently published global fuel consumption data product and updated emission factor measurements. The unique inventory is coupled to an Asia-nested (∼50 km) atmospheric model and used to calculate the global population exposure to BC with fully quantified uncertainty. Evaluating the modeled surface BC concentrations against observations reveals great improvement. The bias is reduced from −88% to −35% in Asia when the unique inventory and higher-resolution model replace a previous inventory combined with a coarse-resolution model. The bias can be further reduced to −12% by downscaling to 10 km using emission as a proxy. Our estimated global population-weighted BC exposure concentration constrained by observations is 2.14 μg⋅m⁻³; 130% higher than that obtained using less detailed inventories and low-resolution models.Black carbon (BC), or soot, emitted from incomplete combustion of carbonaceous fuels is an air pollutant which also plays an important role in climate change (1). BC is an indicator of air particulate pollution and BC in ambient air has an impact on human health (2). In a recent study in China, it was found that the effects of BC on morbidity appear to be more robust than the effects of fine particles in general (3, 4).However, global atmospheric aerosol models often underestimate the concentration of BC at the surface, particularly over Asia, by a factor that typically ranges from 2 to 10 (5–7). In one study, the observed BC surface concentration for China could only be reproduced by doubling the emissions prescribed to a transport model (8). It is often argued that the underestimation is due to a low bias in BC emission inventories, suggesting a need to revisit these previous inventories (9).In a bottom-up approach, BC emission is estimated based on the amount of fuel consumed and an emission factor (EF_BC, defined as the amount of BC emitted per unit mass of fuel consumed) for each of various combustion sources. For previous inventories, the lack of EF_BC measurements in developing countries led to high uncertainty in estimating the total emissions (10). In addition, the use of fuel data at the national level is likely to distort the geographical distribution of emissions within large countries such as China and India (11). Recently, a 0.1° × 0.1° fuel database with 64 types of combustion has been developed based on local or national fuel consumption statistics. This database improves the resolution of the spatial distribution of emissions for large countries (12). To fill the data gap in developing countries, a set of EF_BC values has been compiled for various residential solid fuel combustion devices and vehicles (13–20). In addition to the problems with the emission inventories, the coarse resolution of existing global aerosol models also hinders our ability to capture detailed spatial variation, leading to poor agreement between model prediction and observations (7).In this study we develop and evaluate a unique global BC emission inventory using a zoomed aerosol model, and estimate the global population’s exposure to BC with a focus on Asia. The influence of model resolution and the use of an updated emission inventory on the calculated BC concentration are evaluated against field observations.     

From the Cover: Functional changes of the reward system underlie blunted response to social gaze in cocaine users

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction.Cocaine dependence is a chronically relapsing disorder defined by uncontrolled and compulsive drug use (1). Despite severe negative consequences including disrupted social relationships, loss of employment, and somatic and psychiatric illnesses, an addicted person’s life is often centered around the drug of choice and activities related to it (2). Therefore, drug use is classified as a major social, legal, and public health problem (3). After cannabis, cocaine is the second most prevalent illegal drug in the United States and Europe (4, 5), with a lifetime prevalence among young adults of 6.3% in Europe (15- to 34-y-olds) (4) and 13.3% in the United States (18- to 25-y-olds) (5).Social cognition and social support for drug users are of great clinical relevance, as they have been reported to influence onset of drug use and development of substance use disorders, and treatment success in patients with substance use disorders (6, 7). Impairments in social cognition may augment the risk of social isolation, aggression, and depression, likely supporting the vicious circle of drug use (8). Additionally, impaired social cognition may contribute to the decay of social relationships in addicted patients (9) with negative consequences for treatment success given that higher social support predicted longer abstinence duration (10). Furthermore, no efficient pharmacological treatment for cocaine addiction is currently available (11), and treatment approaches such as cognitive behavioral therapy rely, at least in part, on the emotional responsiveness and social abilities of drug users (12). Previous results suggest that cocaine users (CUs) show impairments in different facets of social cognition, particularly in emotional empathy, mental perspective taking, and emotion recognition in prosody, which are related to deficits in real-life social behavior such as fewer social contacts and more criminal offenses (13, 14). Furthermore, in money distribution games, CUs act more self-servingly and less altruistically than stimulant-naïve controls (15). Volkow et al. (9) postulated that neuroadaptations in the reward systems of drug users (e.g., ventral striatum and orbitofrontal cortex) alter reward processing such that the value of the abused drug is enhanced and concurrently the value of nondrug rewards, including social interaction, is reduced. Consequently, general social competence might become impaired and promote antisocial and criminal behavior. This may explain why social consequences of drug use (e.g., imprisonment or familial problems) do not prompt drug-addicted people to quit using the drug as well as how they contribute to increased drug use and transition from recreational drug use to addiction (9). However, whereas altered processing of monetary rewards has been reported in CUs (16), social reward processing has not been studied yet, neither on the psychological nor the neural level. Therefore, it remains elusive whether CUs (i) show behavioral differences to reward stemming from social interactions and, if so, (ii) which neural adaptations within reward circuitry underlie these potential changes in social interaction behavior.An essential part of social interaction is the phenomenon of “social gaze,” which has two aspects: Gaze can be used by the gazing person as a deictic cue to manipulate the attention of others, and can be read out by observers as a hint toward attentional focus of the gazing person (17). Both aspects can converge in joint attention (JA), which is a central element of social interaction (18) and is established when a person follows the direction of another person’s gaze so that both attend to the same object (19). Engagement in JA is considered to reflect our understanding of another person’s point of view (20). The capacity of JA emerges at 8–12 mo of age (21) and is predictive for later language learning (22) and the development of more advanced social skills such as mental perspective taking (e.g., the attribution of intentions and goals to others, also known as theory of mind) (23). Impaired JA is a core symptom of autism spectrum disorders (24).To test for social gaze differences between CUs and healthy controls (HCs), we applied a paradigm designed to capture the reciprocal and interactive nature of JA (25) (Fig. S1), where participants engage in an online interaction with an anthropomorphic virtual character in real time. Compared with self-initiated nonjoint attention (NJA; i.e., if the counterpart does not follow one’s gaze but rather pays attention to another object), self-initiated JA (i.e., if the counterpart follows one’s own gaze) is perceived as more pleasurable and associated with stronger activation of reward-related brain areas in healthy controls (25). This rewarding nature of JA might underlie the human motivation to engage in the sharing of experiences that emerges in early childhood (22, 25).It has been suggested that changes in social reward processing might underlie alterations in social behavior and cognition in CUs (9). Here we conducted two studies assessing JA processing, which constitutes an elegant approach to investigate basic social interaction patterns related to social reward processing (25), in CUs and stimulant-naïve HCs by means of behavioral, psychophysiological, and functional brain-imaging methods. In study I, a large sample of relatively pure CUs with few psychiatric comorbidities (n = 80) and stimulant-naïve HCs (n = 63) completed an interactive JA task (25) while valence and arousal ratings, error scores, reaction time, and pupil size were obtained. Pupil dilation provides an objective index of affective processing (26, 27). Based on the observations obtained in study I, we further investigated the neural correlates of the blunted emotional response to social gaze in subsamples of 16 CUs and 16 HCs using functional magnetic resonance imaging (fMRI) during an abridged version of the paradigm (study II). We hypothesized that altered emotional responses to JA are accompanied by less pronounced activation in reward-related brain areas of CUs.     

Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) joint consensus statement for MR imaging of placenta accreta spectrum disorders

This study was conducted in order to establish the joint Society of Abdominal Radiology (SAR) and European Society of Urogenital Radiology (ESUR) guidelines on placenta accreta spectrum (PAS) disorders and propose strategies to standardize image acquisition, interpretation, and reporting for this condition with MRI. The published evidence-based data and the opinion of experts were combined using the RAND–UCLA Appropriateness Method and formed the basis for these consensus guidelines. The responses of the experts to questions regarding the details of patient preparation, MRI protocol, image interpretation, and reporting were collected, analyzed, and classified as “recommended” versus “not recommended” (if at least 80% consensus among experts) or uncertain (if less than 80% consensus among experts). Consensus regarding image acquisition, interpretation, and reporting was determined using the RAND–UCLA Appropriateness Method. The use of a tailored MRI protocol and standardized report was recommended. A standardized imaging protocol and reporting system ensures recognition of the salient features of PAS disorders. These consensus recommendations should be used as a guide for the evaluation of PAS disorders with MRI. • MRI is a powerful adjunct to ultrasound and provides valuable information on the topography and depth of placental invasion. • Consensus statement proposed a common lexicon to allow for uniformity in MRI acquisition, interpretation, and reporting of PAS disorders. • Seven MRI features, namely intraplacental dark T2 bands, uterine/placental bulge, loss of low T2 retroplacental line, myometrial thinning/disruption, bladder wall interruption, focal exophytic placental mass, and abnormal vasculature of the placental bed, reached consensus and are categorized as “recommended” for diagnosing PAS disorders.