Treatment of newly diagnosed severe aplastic anemia in children: Evidence-based recommendations.

Severe aplastic anemia (SAA) is a rare potentially fatal hematologic disorder. Although overall outcomes with treatment are excellent, there are variations in management approach, including differences in treatment between adult and pediatric patients. Certain aspects of treatment are under active investigation in clinical trials. Because of the rarity of the disease, some pediatric hematologists may have relatively limited experience with the complex management of SAA. The following recommendations reflect an up-to-date evidence-based approach to the treatment of children with newly diagnosed SAA.

Treatment of relapsed/refractory severe aplastic anemia in children: Evidence-based recommendations.

Severe aplastic anemia (SAA) is a rare potentially fatal hematologic disorder. Although overall outcomes with treatment are excellent, there are variations in management approach, including differences in treatment between adult and pediatric patients. Certain aspects of treatment are under active investigation in clinical trials. Because of the rarity of the disease, some pediatric hematologists may have relatively limited experience with the complex management of SAA. The following recommendations reflect an up-to-date evidence-based approach to the treatment of children with relapsed or refractory SAA.

Relationships Between Running Biomechanics and Femoral Articular Cartilage Thickness and Composition in Anterior Cruciate Ligament Reconstruction Patients.

BACKGROUND: Although individuals with anterior cruciate ligament reconstruction (ACLR) are at high risk for posttraumatic osteoarthritis, mechanisms underlying the relationship between running and knee cartilage health remain unclear. OBJECTIVE: We aimed to investigate how 30 min of running influences femoral cartilage thickness and composition and their relationships with running biomechanics in patients with ACLR and controls. METHODS: Twenty patients with ACLR (time post-ACLR: 14.6 ± 6.1 months) and 20 matched controls participated in the study. A running session required both groups to run for 30 min at a self-selected speed. Before and after running, we measured femoral cartilage thickness via ultrasound imaging. A MRI session consisted of T2 mapping. RESULTS: The ACLR group showed longer T2 relaxation times in the medial femoral condyle at resting compared with the control group (central: 51.2 ± 16.6 vs. 34.9 ± 13.2 ms, p = 0.006; posterior: 50.2 ± 10.1 vs. 39.8 ± 7.4 ms, p = 0.006). Following the run, the ACLR group showed greater deformation in the medial femoral cartilage than the control group (0.03 ± 0.01 vs. 0.01 ± 0.01 cm, p = 0.001). Additionally, the ACLR group showed significant negative correlations between resting T2 relaxation time in the medial femoral condyle and vertical impulse (standardized regression coefficients = -0.99 and p = 0.004) during running. CONCLUSIONS: Our findings suggest that those who are between 6 and 24 months post-ACLR have degraded cartilage composition and their cartilage deforms more due to running vGRF.

Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

Impact of sequencing of androgen receptor-signaling inhibition and radiotherapy in prostate cancer: importance of homologous recombination disruption.

PURPOSE: The synergy of combining androgen receptor-signaling inhibition (ARSI) to radiotherapy (RT) in prostate cancer has been largely attributed to non-homologous end joining (NHEJ) inhibition. However, this mechanism is unlikely to explain recently observed trial results that demonstrated the sequencing of ARSI and RT significantly impacts clinical outcomes, with adjuvant ARSI following RT yielding superior outcomes to neoadjuvant/concurrent therapy. We hypothesized this is driven by differential effects on AR-signaling and alternative DNA repair pathway engagement based on ARSI/RT sequencing. METHODS: We explored the effects of ARSI sequencing with RT (neoadjuvant vs concurrent vs adjuvant) in multiple prostate cancer cell lines using androgen-deprived media and validation with the anti-androgen enzalutamide. The effects of ARSI sequencing were measured with clonogenic assays, AR-target gene transcription and translation quantification, cell cycle analysis, DNA damage and repair assays, and xenograft animal validation studies. RESULTS: Adjuvant ARSI after RT was significantly more effective at killing colony forming cells and decreasing the transcription and translation of downstream AR-target genes across all prostate cancer models evaluated. These results were reproduced in xenograft studies. The differential effects of ARSI sequencing were not fully explained by NHEJ inhibition alone, but by the additional disruption of homologous recombination specifically with adjuvant sequencing of ARSI. CONCLUSION: We demonstrate that altered sequencing of ARSI and RT mediates differential anti-AR-signaling and anti-cancer effects, with the greatest benefit from adjuvant ARSI following RT. These results, combined with our prior clinical findings, support the superiority of an adjuvant-based sequencing approach when using ARSI with RT.

Quantitative background parenchymal enhancement and fibro-glandular density at breast MRI: Association with BRCA status.

OBJECTIVES: To investigate whether MRI-based measurements of fibro-glandular tissue volume, breast density (MRBD), and background parenchymal enhancement (BPE) could be used to stratify two cohorts of healthy women: BRCA carriers and women at population risk of breast cancer. METHODS: Pre-menopausal women aged 40-50 years old were scanned at 3 T, employing a standard breast protocol including a DCE-MRI (35 and 30 participants in high- and low-risk groups, respectively). The dynamic range of the DCE protocol was characterised and both breasts were masked and segmented with minimal user input to produce measurements of fibro-glandular tissue volume, MRBD, and voxelwise BPE. Statistical tests were performed to determine inter- and intra-user repeatability, evaluate the symmetry between metrics derived from left and right breasts, and investigate MRBD and BPE differences between the high- and low-risk cohorts. RESULTS: Intra- and inter-user reproducibility in estimates of fibro-glandular tissue volume, MRBD, and median BPE estimations were good, with coefficients of variation < 15%. Coefficients of variation between left and right breasts were also low (< 25%). There were no significant correlations between fibro-glandular tissue volume, MRBD, and BPE for either risk group. However, the high-risk group had higher BPE kurtosis, although linear regression analysis did not reveal significant associations between BPE kurtosis and breast cancer risk. CONCLUSIONS: This study found no significant differences or correlations in fibro-glandular tissue volume, MRBD, or BPE metrics between the two groups of women with different levels of breast cancer risk. However, the results support further investigation into the heterogeneity of parenchymal enhancement. KEY POINTS: • A semi-automated method enabled quantitative measurements of fibro-glandular tissue volume, breast density, and background parenchymal enhancement with minimal user intervention. • Background parenchymal enhancement was quantified over the entire parenchyma, segmented in pre-contrast images, thus avoiding region selection. • No significant differences and correlations in fibro-glandular tissue volume, breast density, and breast background parenchymal enhancement were found between two cohorts of women at high and low levels of breast cancer risk.

Evaluating the Implementation of a Medical Student's Handoff Curriculum During the Surgery Clerkship.

INTRODUCTION: Early introduction to essential communication skills is important. We sought to determine if a handoff curriculum (HC) would improve confidence, decrease anxiety, and increase participation in clinical handoffs during the surgical clerkship. METHODS: A multi-center prospective cohort study was performed at two medical schools. Training in the intervention group (HC) consisted of a didactic lecture, video review, and practice session. Students completed a pre-clerkship knowledge test and confidence/anxiety/handoff experience questionnaire pre- and post-clerkship. RESULTS: There were no significant differences in pre-clerkship handoff experiences between institutions except having previously witnessed a verbal handoff (School A 96.4% versus School B 76.2%, P = 0.01). While there were no significant differences in post-clerkship confidence or anxiety, HC students were significantly more involved with written sign-outs (52.9% versus 18.2%, P = 0.02) and verbal handoffs (29.4% versus 4.6%, P = 0.03). CONCLUSIONS: Medical students exposed to handoff training shared similar confidence and anxiety scores compared to those that were not, however, they were more involved in handoff experiences during their surgical clerkship. Early introduction to handoff skills may encourage greater participation during subsequent clinical experiences.

Impact of moral injury and posttraumatic stress disorder on health care utilization and suicidality in rural and urban veterans.

This study explored the impact of moral injury (MI) and posttraumatic stress disorder (PTSD) on health care utilization, mental health complexity, and suicidality in rural and urban veterans. Analyses combined data from the Salt Lake City PTSD Clinic Intake Database and the Department of Veterans Affairs Corporate Data Warehouse. Participants (N = 1,545; Mage = 45.9 years) were predominately male (88.3%) and White (87.8%). Adjusted analyses indicated associations between a 1-unit increase in Moral Injury Events Scale (MIES) score and increased mental health complexity, RR = 1.01, 95% CI [1.01, 1.02], p < .001; psychotropic medication utilization, RR = 1.01, 95% CI [1.01, 1.03], p < .001; VA drug class count, RR = 1.01, 95% CI [1.00, 1.01], p = .030; outpatient utilization, RR = 1.01, 95% CI [1.01, 1.02], p < .001; and mental health outpatient utilization, RR = 1.01, 95% CI [1.00, 1.03], p < .001. For the MIES x PTSD interaction, all associations remained statistically significant with similar estimated effects. However, for rural veterans, this interaction did not significantly affect utilization. Among those with PTSD, a 1-unit MIES increase was associated with an increased risk of suicidality, OR = 1.02, 95% CI [1.01, 1.04], and psychiatric admission, OR = 1.02, 95% CI [1.00, 1.04]. Findings suggest that higher MIES scores predict increased health care utilization and mental health complexity. Further, PTSD combined with higher MIES scores may increase the risk of suicidality and psychiatric admission. Rural veterans with PTSD and higher MIES scores may require additional outreach and intervention.

Collaboration in interprofessional teams: A needs assessment of factors that impact new resident physicians.

Many resident physicians struggle with effective interprofessional collaboration (IPC), but characterization of their challenges is not well known. This study examines gaps in IPC skills for graduating medical students entering residency. A needs assessment was completed to evaluate factors that impact resident physicians' ability to effectively collaborate with other healthcare professionals. This study included online surveys of 123 recent medical school graduates, 21 semi-structured interviews of residency program directors, and 3 focus groups of healthcare professionals who interacted with residents. Survey results were analyzed for means and narratives from surveys, interviews, and focus groups were analyzed for themes. We found that graduates felt they did not have a strong understanding of other providers' roles and did not feel well prepared to handle conflict with other providers or navigate interprofessional team dynamics. Themes emerging from narrative data generally aligned with the Interprofessional Education Collaborative core competencies including understanding team roles, communicating effectively, and working effectively in a team, but these interviews also elucidated an additional theme, overcoming system barriers. Data from this work can inform curricula in preparation for the transition to residency. The authors also offer an educational framework for learning effective IPC as a new team member.

SPRING-RIO TSE: 2D T2 -Weighted Turbo Spin-Echo brain imaging using SPiral RINGs with retraced in/out trajectories.

PURPOSE: To develop a new approach to 2D turbo spin -echo (TSE) imaging using annular spiral rings with a retraced in/out trajectory, dubbed "SPRING-RIO TSE", for fast T2 -weighted brain imaging at 3T. METHODS: A long spiral trajectory was split into annular segmentations that were then incorporated into a 2D TSE acquisition module to fully exploit the sampling efficiency of spiral rings. A retraced in/out trajectory strategy coupled with spiral-ring TSE was introduced to increase SNR, mitigate T2 -decay induced artifacts, and self-correct moderate off-resonance while maintaining the target TE and causing no scan time penalty. Model-based k-space estimation and semiautomatic off-resonance correction algorithms were implemented to minimize effects of k-space trajectory infidelity and B0 inhomogeneity, respectively. The resulting SPRING-RIO TSE method was compared to the original spiral-ring (abbreviated "SPRING") TSE and Cartesian TSE using simulations, and phantom and in vivo acquisitions. RESULTS: Simulation and phantom studies demonstrated the performance of the proposed SPRING-RIO TSE pulses sequence, as well as that of trajectory correction and off-resonance correction. Volunteer data showed that the proposed method achieves high-quality 2D T2 -weighted brain imaging with a higher scan efficiency (0:45 min/14 slices versus 1:31 min/14 slices), improved image contrast, and reduced specific absorption rate compared to conventional 2D Cartesian TSE. CONCLUSION: 2D T2 -weighted brain imaging using spiral-ring TSE was implemented and tested, providing several potential advantages over conventional 2D Cartesian TSE imaging.

A review on the added value of whole-body MRI in metastatic lobular breast cancer.

Invasive lobular breast carcinomas (ILC) account for approximately 15% of breast cancer diagnoses. They can be difficult to diagnose both clinically and radiologically, due to their infiltrative growth pattern. The pattern of metastasis of ILC is unusual, with spread to the serosal surfaces (pleura and peritoneum), retroperitoneum and gastrointestinal (GI)/genitourinary (GU) tracts and a higher rate of leptomeningeal spread than IDC. Routine staging and response assessment with computed tomography (CT) can be undertaken quickly and measurements can be reproduced easily, but this is challenging with metastatic ILC as bone-only/bone-predominant patterns are frequently seen and assessment of the disease status is limited in these scenarios. Functional imaging such as whole-body MRI (WBMRI) allows the assessment of bone and soft tissue disease by providing functional information related to differences in cellular density between malignant and benign tissues. A number of recent studies have shown that WBMRI can detect additional sites of disease in metastatic breast cancer (MBC), resulting in a change in systemic anti-cancer therapy. Although WBMRI and fluorodeoxyglucose-positron-emission tomography-computed tomography (FDG-PET/CT) have a comparable performance in the assessment of MBC, WBMRI can be particularly valuable as a proportion of ILC are non-FDG-avid, resulting in the underestimation of the disease extent. In this review, we explore the added value of WBMRI in the evaluation of metastatic ILC and compare it with other imaging modalities such as CT and FDG-PET/CT. We also discuss the spectrum of WBMRI findings of the different metastatic sites of ILC with CT and FDG-PET/CT correlation. KEY POINTS: • ILC has an unusual pattern of spread compared to IDC, with metastases to the peritoneum, retroperitoneum and GI and GU tracts, but the bones and liver are the commonest sites. • WBMRI allows functional assessment of metastatic disease, particularly in bone-only and bone-predominant metastatic cancers such as ILC where evaluation with CT can be challenging and limited. • WBMRI can detect more sites of disease compared with CT, can reveal disease progression earlier and provides the opportunity to change ineffective systemic treatment sooner.

Frequency and Characteristics of Social Media Use among General Surgery Trainees.

INTRODUCTION: With increased social isolation due to COVID-19, social media has been increasingly adopted for communication, education, and entertainment. We sought to understand the frequency and characteristics of social media usage among general surgery trainees. MATERIALS AND METHODS: General surgery trainees in 15 American training programs were invited to participate in an anonymous electronic survey. The survey included questions about demographics, frequency of social media usage, and perceptions of risks and benefits of social media. Univariate analysis was performed to identify differences between high users of social media (4-7 h per week on at least one platform) and low users (0-3 h or less on all platforms). RESULTS: One hundred fifty-seven of 591 (26.6%) trainees completed the survey. Most respondents were PGY3 or lower (75%) and high users of social media (74.5%). Among high users, the most popular platforms were Instagram (85.7%), YouTube (85.1%), and Facebook (83.6%). YouTube and Twitter were popular for surgical education (77.3% and 68.2%, respectively). The most reported benefits of social media were improving patient education and professional networking (85.0%), where high users agreed more strongly about these benefits (P = 0.002). The most reported risks were seeing other residents (42%) or attendings (17%) with unprofessional behavior. High users disagreed more strongly about risks, including observing attendings with unprofessional behavior (P = 0.028). CONCLUSIONS: Most respondents were high users of social media, particularly Instagram, YouTube, and Facebook. High users incorporated social media into their surgical education while perceiving more benefits and fewer risks of social media.

Multiplex accurate sensitive quantitation (MASQ) with application to minimal residual disease in acute myeloid leukemia.

Measuring minimal residual disease in cancer has applications for prognosis, monitoring treatment and detection of recurrence. Simple sequence-based methods to detect nucleotide substitution variants have error rates (about 10-3) that limit sensitive detection. We developed and characterized the performance of MASQ (multiplex accurate sensitive quantitation), a method with an error rate below 10-6. MASQ counts variant templates accurately in the presence of millions of host genomes by using tags to identify each template and demanding consensus over multiple reads. Since the MASQ protocol multiplexes 50 target loci, we can both integrate signal from multiple variants and capture subclonal response to treatment. Compared to existing methods for variant detection, MASQ achieves an excellent combination of sensitivity, specificity and yield. We tested MASQ in a pilot study in acute myeloid leukemia (AML) patients who entered complete remission. We detect leukemic variants in the blood and bone marrow samples of all five patients, after induction therapy, at levels ranging from 10-2 to nearly 10-6. We observe evidence of sub-clonal structure and find higher target variant frequencies in patients who go on to relapse, demonstrating the potential for MASQ to quantify residual disease in AML.

Validity of ultrasound imaging for intrinsic foot muscle cross-sectional area measurements demonstrated by strong agreement with MRI.

PURPOSE: Intrinsic foot muscles maintain foot structural integrity and contribute to functional movement, posture and balance. Thus, assessing intrinsic foot muscle size and strength are important. Magnetic resonance imaging (MRI) has been shown to accurately image the individual muscles but is costly and time consuming. Ultrasound (US) imaging may provide an alternative that is less costly and more readily available. The purpose of this study was to investigate the validity and intratester reliability of US imaging in measuring intrinsic foot muscle size in comparison to MRI. METHODS: US and MRI were employed to measure the intrinsic foot muscle size involving 35 participants (females = 13; males = 22). The scanned intrinsic foot muscles included the flexor hallucis brevis (FHB), abductor hallucis (ABDH), flexor digitorum brevis (FDB), quadratus plantae (QP) and abductor digiti minimi (ADM). Pearson product correlation (r), intraclass correlation coefficients (ICC), standard error of the measurement (SEm) and minimal detectable difference (MDD) were calculated. RESULTS: High correlations were detected between the US and MRI cross-sectional area (CSA) measurements (r = .971 to 0.995). Test reliability was excellent for both MRI and US (ICC = 0.994 to 0.999). Limits of agreement between MRI and US measurements from ranged from 5.7 to 12.2% of muscle size. SEm values for US ranged from 0.026 to 0.044 cm2, while the SEm for MRI ranged from 0.018 to 0.023 cm2. MDD values for US ranged from 0.073 to 0.122 cm2, while MRI ranged from 0.045 to 0.064 cm2. CONCLUSIONS: US appears to be a valid and reliable alternative to MRI when measuring intrinsic foot muscle CSA. While US is less costly and more readily available, the MRI results were shown to be slightly more precise.

A chronic eyelid lesion in a child: multi-disciplinary approach to diagnosis, treatment and management of a highly atypical histiocytic lesion.

Malignant histiocytic neoplasm with histiocytic sarcoma phenotype is a rare malignant neoplasm, distinguished by malignant cells with phenotypic characteristics of mature tissue histiocytes. Histiocytic sarcoma typically presents as a primary malignancy, although can also present as a secondary malignancy, and is rarely seen in the pediatric population. Due to the rarity of this condition, diagnosis of histiocytic sarcoma is difficult and considered a diagnosis of exclusion. We describe a unique case of a chronic upper eyelid lesion with biopsy findings of a highly atypical histiocytic neoplasm initially concerning for histiocytic sarcoma; however, after integration of clinical findings, non-progressive and quiescent molecular profile, concluded to be an atypical juvenile xanthogranuloma in a child treated with excision and observation alone. This report highlights the importance of an integrated team approach to diagnosis of unusual histiocytic neoplasms.

Making and shaping endochondral and intramembranous bones.

Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and vocalization. The precise positioning, size, and shape of skeletal elements is therefore critical for their function. During embryonic development, bone forms by endochondral or intramembranous ossification and can arise from the paraxial and lateral plate mesoderm or neural crest. This review describes inductive mechanisms to position and pattern bones within the developing embryo, compares and contrasts the intrinsic vs extrinsic mechanisms of endochondral and intramembranous skeletal development, and details known cellular processes that precisely determine skeletal shape and size. Key cellular mechanisms are employed at distinct stages of ossification, many of which occur in response to mechanical cues (eg, joint formation) or preempting future load-bearing requirements. Rapid shape changes occur during cellular condensation and template establishment. Specialized cellular behaviors, such as chondrocyte hypertrophy in endochondral bone and secondary cartilage on intramembranous bones, also dramatically change template shape. Once ossification is complete, bone shape undergoes functional adaptation through (re)modeling. We also highlight how alterations in these cellular processes contribute to evolutionary change and how differences in the embryonic origin of bones can influence postnatal bone repair.

Systemic and Nodular Hyperinflammation in a Patient with Refractory Familial Hemophagocytic Lymphohistiocytosis 2.

Familial hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome resulting from defective cytotoxicity. A previously healthy 3-month-old female presented with fever, irritability, abdominal distention, and tachypnea. She ultimately met all eight HLH-2004 diagnostic criteria, accompanied by elevated CXCL9. Initial empiric anti-inflammatory treatment included anakinra and IVIg, which stabilized ferritin and cytopenias. She had molecular and genetic confirmation of perforin deficiency and was started on dexamethasone and etoposide per HLH-94. She clinically improved, though CXCL9 and sIL-2Ra remained elevated. She was readmitted at week 8 for relapsed HLH without clear trigger and HLH-94 induction therapy was reinitiated. Her systemic HLH symptoms failed to respond and she soon developed symptomatic CNS HLH. She was incidentally found to have multifocal lung and kidney nodules, which were sterile and consisted largely of histiocytes and activated, oligoclonal CD8 T cells. The patient had a laboratory response to salvage therapy with alemtuzumab and emapalumab, but progressive neurologic decline led to withdrawal of care. This report highlights HLH foci manifest as pulmonary/renal nodules, demonstrates the utility of monitoring an array of HLH biomarkers, and suggests possible benefit of earlier salvage therapy.

A preclinical study of diffusion-weighted MRI contrast as an early indicator of thermal ablation.

PURPOSE: Intraoperative T2 -weighted (T2-w) imaging unreliably captures image contrast specific to thermal ablation after transcranial MR-guided focused ultrasound surgery, impeding dynamic imaging feedback. Using a porcine thalamotomy model, we test the unproven hypothesis that intraoperative DWI can improve dynamic feedback by detecting lesioning within 30 minutes of transcranial MR-guided focused ultrasound surgery. METHODS: Twenty-five thermal lesions were formed in six porcine models using a clinical transcranial MR-guided focused ultrasound surgery system. A novel diffusion-weighted pulse sequence monitored the formation of T2-w and diffusion-weighted lesion contrast after ablation. Using postoperative T2-w contrast to indicate lesioning, apparent intraoperative image contrasts and diffusion coefficients at each lesion site were computed as a function of time after ablation, observed peak temperature, and observed thermal dose. Lesion sizes segmented from imaging and thermometry were compared. Image reviewers estimated the time to emergence of lesion contrast. Intraoperative image contrasts were analyzed using receiver operator curves. RESULTS: On average, the apparent diffusion coefficient at lesioned sites decreased within 5 minutes after ablation relative to control sites. In-plane lesion areas on intraoperative DWI varied from postoperative T2-w MRI and MR thermometry by 9.6±9.7 mm2 and -4.0±7.1 mm2 , respectively. The 0.25, 0.5, and 0.75 quantiles of the earliest times of observed T2-w and diffusion-weighted lesion contrast were 10.7, 21.0, and 27.8 minutes and 3.7, 8.6, and 11.8 minutes, respectively. The T2-w and diffusion-weighted contrasts and apparent diffusion coefficient values produced areas under the receiver operator curve of 0.66, 0.80, and 0.74, respectively. CONCLUSION: Intraoperative DWI can detect MR-guided focused ultrasound surgery lesion formation in the brain within several minutes after treatment.

Should intramuscular clozapine be adopted into mainstream clinical practice?

Clozapine is under-used in the UK, and Casetta et al's recent paper in the BJPsych adds to a growing number of small studies that support the use of intramuscular clozapine to initiate and maintain treatment with oral clozapine. However, intramuscular clozapine remains unlicensed and, because of the risks associated with its administration, it should be used only cautiously before it can be adopted more widely into mainstream clinical practice.

Diagnostic work-up for severe aplastic anemia in children: Consensus of the North American Pediatric Aplastic Anemia Consortium.

The North American Pediatric Aplastic Anemia Consortium (NAPAAC) is a group of pediatric hematologist-oncologists, hematopathologists, and bone marrow transplant physicians from 46 institutions in North America with interest and expertise in aplastic anemia, inherited bone marrow failure syndromes, and myelodysplastic syndromes. The NAPAAC Bone Marrow Failure Diagnosis and Care Guidelines Working Group was established with the charge of harmonizing the approach to the diagnostic workup of aplastic anemia in an effort to standardize best practices in the field. This document outlines the rationale for initial evaluations in pediatric patients presenting with signs and symptoms concerning for severe aplastic anemia.