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Seizures have been reported as an adverse effect of blinatumomab, a bispecific T-cell engager monoclonal antibody, which is mainly used for the treatment of pediatric relapsed/refractory leukemia. Here, we present the first reported case of super-refractory status epilepticus in an 11-year-old boy with B-cell acute lymphoblastic leukemia (B-ALL) while receiving blinatumomab. Our patient had a complete return to baseline despite enduring encephalopathy, refractory subclinical seizures requiring prolonged therapeutic burst suppression and MRI signal changes. This case demonstrates that super-refractory status epilepticus is a possible neurotoxic adverse effect of blinatumomab treatment, which responds well to conventional protocols for acute refractory seizures.Seizures are a known side effect of blinatumomab, a relatively new immunotherapy drug, which is mainly used for the treatment of relapsed leukemia in children. Here, we present the first reported case of seizure continuing for more than 24 h despite appropriate antiseizure treatment while also receiving blinatumomab. Despite an extended period of altered mental status, new abnormalities on imaging of the brain and a medication-induced coma to treat unrelenting seizures, our patient returned completely to his healthy brain function. This case demonstrates that seizures, which are especially difficult to treat, can be associated with blinatumomab immunotherapy for pediatric refractory B-ALL; however, standard-tiered seizure treatments can be effective.

We exploit a suite of large \emph{N}-body simulations (up to N=$4096^3$) performed with \Abacus, of scale-free models with a range of spectral indices $n$, to better understand and quantify convergence of the matter power spectrum. Using self-similarity to identify converged regions, we show that the maximal wavenumber resolved at a given level of accuracy increases monotonically as a function of time. At the 1\% level it starts at early times from a fraction of $k_\Lambda$, the Nyquist wavenumber of the initial grid, and reaches at most, if the force softening is sufficiently small, $\sim 2-3 k_\Lambda$ at the very latest times we evolve to. At the $5\%$ level, accuracy extends up to wavenumbers of order $5k_\Lambda$ at late times. Expressed as a suitable function of the scale-factor, accuracy shows a very simple $n$-dependence, allowing a extrapolation to place conservative bounds on the accuracy of \emph{N}-body simulations of non-scale free models like LCDM. We note that deviations due to discretization in the converged range are not well modelled by shot noise, and subtracting it in fact degrades accuracy. Quantitatively our findings are broadly in line with the conservative assumptions about resolution adopted by recent studies using large cosmological simulations (e.g. Euclid Flagship) aiming to constrain the mildly non-linear regime. On the other hand, we remark that conclusions about small scale clustering (e.g. concerning the validity of stable clustering) obtained using PS data at wavenumbers larger than a few $k_\Lambda$ may need revision in light of our convergence analysis., Comment: 14 pages, 10 figures, version to match published version. Additional subsection in Shot noise and discreteness effects

Chronic graft-versus-host disease (cGVHD) is the most common cause for non-relapse mortality postallogeneic hematopoietic stem cell transplant (HSCT). However, there are no well-defined biomarkers for cGVHD or late acute GVHD (aGVHD). This study is a longitudinal evaluation of metabolomic patterns of cGVHD and late aGVHD in pediatric HSCT recipients. A quantitative analysis of plasma metabolites was performed on 222 evaluable pediatric subjects from the ABLE/PBMTC1202 study. We performed a risk-assignment analysis at day + 100 (D100) on subjects who later developed either cGVHD or late aGVHD after day 114 to non-cGVHD controls. A second analysis at diagnosis used fixed and mixed multiple regression to compare cGVHD at onset to time-matched non-cGVHD controls. A metabolomic biomarker was considered biologically relevant only if it met all 3 selection criteria: (1) P ≤ .05; (2) effect ratio of ≥1.3 or ≤0.75; and (3) receiver operator characteristic AUC ≥0.60. We found a consistent elevation in plasma α-ketoglutaric acid before (D100) and at the onset of cGVHD, not impacted by cGVHD severity, pubertal status, or previous aGVHD. In addition, late aGVHD had a unique metabolomic pattern at D100 compared with cGVHD. Additional metabolomic correlation patterns were seen with the clinical presentation of pulmonary, de novo, and progressive cGVHD. α-ketoglutaric acid emerged as the single most significant metabolite associated with cGVHD, both in the D100 risk-assignment and later diagnostic onset analysis. These distinctive metabolic patterns may lead to improved subclassification of cGVHD. Future validation of these exploratory results is needed. This trial was registered at www.clinicaltrials.gov as #NCT02067832.

The NIH Consensus Criteria for chronic graft-versus-host disease (cGVHD) diagnosis can be challenging to apply in children. We aimed to discover diagnostic pediatric cGVHD biomarkers that would complement clinical criteria and differentiate cGVHD from non-cGVHD diagnoses. The Applied Biomarkers of Late Effects of Childhood Cancer (ABLE) study (27 transplant centers) prospectively evaluated 302 pediatric patients after hematopoietic cell transplant (234 evaluable). Forty-four patients developed cGVHD. Mixed and fixed effect regression analyses were performed on diagnostic cGVHD onset blood samples for cellular and plasma biomarkers, with individual markers declared relevant if they met three criteria: an effect ratio ≥1.3 or ≤0.75; an area under the curve (AUC) of ≥0.60; and a p-value

Objectives Thoracostomy is often a required treatment in patients with thoracic trauma; however, performing a thoracostomy using traditional techniques can have complications. Ultrasound can be a beneficial tool for identifying the correct thoracostomy insertion site. We designed a randomized prospective study to assess if ultrasound guidance can improve thoracostomy site identification over traditional techniques. Methods Emergency medicine residents were randomly assigned to use palpation or ultrasound to identify a safe insertion site for thoracostomy placement. The target population comprised of hemodynamically stable trauma patients who received an extended focused assessment with sonography for trauma (EFAST) and a chest computed tomography (CT) exam. The resident placed a radiopaque marker on the skin of the patient where a safe intercostal space was believed to be located, either by palpation or ultrasound. Clinical ultrasound faculty reviewed the CT to confirm marker placement relative to the diaphragm. A Fischer's exact test was used to analyze the groups. Results One hundred and forty-seven patients were enrolled in the study, 75 in the ultrasound group and 72 in the landmark group. This resulted in the placement of 271 total thoracostomy site markers, 142 by ultrasound and 129 by palpation and landmarks. The ultrasound group correctly identified thoracostomy insertion sites above the diaphragm in 97.2% (138/142) of patients, while the palpation group identified a safe insertion site in 88.4% (114/129) of patients (P = .0073). Conclusion This study found that emergency medicine residents are more likely to identify a safe tube thoracostomy insertion site in trauma patients by using ultrasound, as compared to using landmarks and palpation.

Despite intensive management, the increasing conflict between humans and saltwater crocodiles in places such as Queensland, Australia, has led to the investigation of alternative techniques to improve public safety. The reliability of digital video surveillance systems (DV) placed above water and multi-beam sonar (sonar) placed under water to detect and monitor saltwater crocodiles was tested in a seminatural freshwater environment over a 2 h period (16:00–18:00 h). A total of 29 crocodiles were detected within the study area using DV, and 28 with sonar. One was obscured by a section of bank, and thus not visible on sonar. Of the 28 crocodiles detected by both methods, sonar recorded both entry and exit for all, while DV recorded both entry and exit for 15 crocodiles. The length of time that crocodiles were detected was longer on average for sonar (4 min 27 s) compared with DV (2 min 50 s). This reflected the time spent above (detected by sonar and DV) or below water (not detected by DV), as only sonar was able to detect crocodiles underwater. The use of sonar may provide a valuable management tool for detecting and monitoring saltwater crocodiles in areas frequented by people (e.g. beaches, boat ramps, upper freshwater areas) where there is a high chance of a negative interaction.

Objectives Ultrasound (US)-only confirmation of central venous catheter (CVC) placement has proven to be accurate and fast when compared with the current standard chest radiograph. This procedure depends on the detection of appropriately timed atrial bubbles during central line flushing, called the rapid atrial swirl sign (RASS). The most obvious barrier to increasing the use of this technique is appropriate education and training; therefore, we proposed a novel educational approach to training emergency department (ED) physicians in the confirmation of CVC location using US and then tested its effectiveness. Methods Using an online educational model, participants were taught the background and procedural steps to confirm CVC placement using US. Subsequently, they were asked to use this knowledge to place central lines in simulation and confirm them using US. They were tested with various scenarios, including correctly and incorrectly placed lines. Their accuracy was measured, and a survey was used to assess their satisfaction with the training and applicability to practice. Results A total of 47 ED physicians completed the online training module and 24 completed the simulation testing that followed. Results showed 100% accuracy in detecting appropriately timed RASS ( 2 seconds), and no RASS in simulation. All of the participants "agreed" or "strongly agreed" that the didactic and simulation sessions improved their understanding of US confirmation of central line placement. Conclusions The use of US to confirm central line placement can be effectively taught to ED physicians using short didactic and simulation-based training. This is a reasonable approach to integrate this protocol into practice, and allow for more widespread use of this emerging technique.

The aim of this study is to systematically compare rates of erosion and chronic pain after mesh insertion for pelvic organ prolapse (POP) and stress urinary incontinence (SUI) surgery. A systematic electronic search was performed on studies that evaluated the incidence of erosion and chronic pain after mesh insertion for POP or SUI. The primary outcome measurement was to compare mesh erosion rates for POP and SUI surgery. Secondary outcome measurements were incidence of de novo pain and a comparison of patient demographics for both surgeries. Twenty-six studies on 292,606 patients (n = 9077 for POP surgery and n = 283,529 for SUI surgery) met the inclusion criteria. Median follow-up was 26.38 ± 22.17 months for POP surgery and 39.33 ± 27.68 months for SUI surgery. Overall, the POP group were older (p

Symptomatic stress urinary incontinence (SUI) and pelvic organ prolapse (POP) refractory to conservative management with pelvic floor muscle training or vaginal pessaries may warrant surgical intervention with different forms of biologic or synthetic material. However, in recent years, several global regulatory agencies have issued health warnings and recalled several mesh products due to an increase in complications such as mesh erosion, infection, chronic pain, and perioperative bleeding. At present, current surgical treatment strategies for SUI and POP are aimed at developing biological graft materials with similar mechanical properties to established synthetic meshes, but with improved tissue integration and minimal host response. This narrative review aims to highlight recent studies related to the development of biomimetic and biologic graft materials as alternatives to traditional synthetic materials for SUI/POP repair in female patients. We also investigate complications and technical limitations associated with synthetic mesh and biological biomaterials in conventional SUI and POP surgery. Our findings demonstrate that newly developed biologic grafts have a lower incidence of adverse events compared to synthetic biomaterials. However there remains a significant disparity between success in preclinical trials and long-term clinical translation. Further characterization on the optimal structural, integrative, and mechanical properties of biological grafts is required before they can be reliably introduced into clinical practice for SUI and POP surgery. Impact statement Our review article aims to outline the clinical history of developments and controversies associated with the use of synthetic mesh materials in the surgical treatment of stress urinary incontinence and pelvic organ prolapse, as well as highlighting recent advancements in the area of biological graft materials and their potential importance in an area that remains an enduring issue for patients and clinicians alike. This article aims to provide a concise summary of previous controversies in the field of urinary incontinence, while evaluating the future of potential biomaterials in this field.

OBJECTIVES We evaluated the utility of focused cardiac ultrasound to predict the length of stay in patients presenting to the emergency department with dyspnea of unclear etiology. METHODS Patients with focused cardiac ultrasound examinations performed in the emergency department for dyspnea over a 34-month period were retrospectively identified. Patients were excluded if they had a prior diagnosis of heart failure, dialysis requirement, or an etiology of dyspnea unrelated to the volume status. Left ventricular function was categorized as normal or reduced, and the inferior vena cava was categorized as normal or increased volume. A fast limited ultrasound to investigate dyspnea (FLUID) score was calculated by adding 1 point for reduced left ventricular function and 1 point for increased volume, producing a score of 0, 1, or 2. RESULTS There were 123 patients included. There was a significant correlation between the FLUID score and length of stay, with longer stays for higher scores (FLUID score 0, 7.4 hours median; FLUID score 1, 2.34 days; FLUID score 2, 5.56 days; analysis of variance P

Background Local relapse is a predominant form of recurrence among pediatric patients with Hodgkin lymphoma (PHL). Although PHL radiotherapy doses have been approximately 20 Gy, adults with Hodgkin lymphoma receiving 30 to 36 Gy experience fewer in-field relapses. We investigated the dosimetric effect of such a dose escalation to the organs at risk (OARs). Materials and Methods Ten patients with PHL treated with proton therapy to 21 Gy involved-site radiation therapy (ISRT21Gy) were replanned to deliver 30 Gy by treating the ISRT to 30 Gy (ISRT30Gy), delivering 21 Gy to the ISRT plus a 9-Gy boost to postchemotherapy residual volume (rISRTboost), and delivering 30 Gy to the residual ISRT target only (rISRT30Gy). Radiation doses to the OARs were compared. Results The ISRT30Gy escalated the dose to the target by 42% but also to the OARs. The rISRTboost escalated the residual target dose by 42%, and the OAR dose by only 17% to 26%. The rISRT30Gy escalated the residual target dose by 42% but reduced the OAR dose by 25% to 46%. Conclusion Boosting the postchemotherapy residual target dose to 30Gy can allow for dose escalation with a slight OAR dose increase. Treating the residual disease for the full 30Gy, however, would reduce the OAR dose significantly compared with ISRT21Gy. Studies should evaluate these strategies to improve outcomes and minimize the late effects.

This paper examines how shocks to government bond duration risk held by price‐sensitive investors affect the euro area term structure of interest rates and the wider macroeconomy. We construct a new measure of the bond “free float,” which adjusts total debt for foreign official holdings and weights by residual maturity. Using a small macrofinance Bayesian Vector Autoregression (VAR) model, we estimate that the first round of asset purchases under the European Central Bank's (ECB) public sector purchase program reduced euro area 10‐year bond yields by around 30 bps in 2015. The positive impact on the output gap and inflation in 2016 was about 0.2 and 0.3 ppt, respectively.

Background In 2008 the Council of Emergency Medicine Residency Directors delineated consensus recommendations for training in biliary ultrasound for the “detection of biliary pathology”. Objectives While studies have looked at the accuracy of emergency provider performed clinical ultrasound (ECUS), we sought to evaluated if ECUS could be diagnostic for acute cholecystitis and thus obviate the need for follow-up imaging. Method We reviewed all ECUS performed between 2012 and 2017 that had a matching radiology performed ultrasound (RADUS) and a discharge diagnosis. 332 studies were identified. The sensitivity and specificity of both ECUS and RADUS were compared to the patient’s discharge diagnosis. The agreement between the ECUS and RADUS was assessed using an unweighted Cohen’s Kappa. The time from patient arrival to diagnosis by ECUS and RADUS was also compared. Results Using discharge diagnosis as the gold standard ECUS was 67% (56–78%) sensitive, 88% (84–92%) specific, NPV 90% (87–95%), PPV 60% (50–71%), +LR 5.6 (3.9–8.2), −LR 0.37 (0.27–0.52) for acute cholecystitis. RADUS was 76% (66–87%) sensitive, 97% (95–99%) specific, NPV 95% (092–97%), PPV 86% (76–95%), +LR 25.6 (12.8–51.4), and −LR 0.24 (0.15–0.38). ECUS was able to detect gallstones with 93% (89–96%) sensitivity and 94% (90–98%) specificity leading to a NPV 90% (85–95%), PPV of 95% (92–98%), +LR 14.5 (7.7–27.4), −LR 0.08 (0.05–0.13). The unweighted kappa between ECUS and RADUS was 0.57. The median time between obtaining ECUS vs. RADUS diagnosis was 124 min. Conclusions ECUS can be beneficial in ruling out acute cholecystitis, but lacks the test characteristics to be diagnostic for acute cholecystitis.

In this paper we assess the macroeconomic effects of two of the flagship unconventional monetary policies used by the Bank of England during the later stages of the global economic crisis: additional Quantitative Easing (QE) and the introduction of the Funding for Lending Scheme (FLS). We argue that these policies can be seen as complements, as QE effectively bypasses the banks by attempting to reduce risk-free yields directly in order to have a wider effect on asset prices, while FLS operates directly through banks by reducing their funding costs and increasing incentives to lend. We attempt to quantify the effects of these policies by estimating their impact on long-term interest rates and bank funding costs, respectively, and then tracing out their wider effects on the macroeconomy using simulations from a large Bayesian vector autoregression (VAR), which are cross-checked with a simpler Auto-regressive distributed lag (ARDL) approach. We find that the second round of the Bank's QE purchases during 2011-12 and the initial phase of the FLS each boosted GDP in the UK by around 0.5%-0.8%. Their effect on inflation was also broadly positive reaching around 0.6 pp, at its peak.

BACKGROUND Previous studies have explored posthematopoietic cell transplant (HCT) outcomes by race in adults; however, pediatric data addressing this topic are scarce. PROCEDURE This retrospective registry study included 238 White (W) and 57 Black (B) children with hematologic malignancies (HM) receiving first allogeneic HCT between 2010 and 2019 at one of the five Florida pediatric HCT centers. RESULTS We found no differences between W and B children in transplant characteristics, other than donor type. There was a significant difference in use of human leukocyte antigen (HLA)-mismatched donors (HLA-MMD) (53% W, 71% B, p = .01). When comparing HLA-MMD use to fully HLA-matched donors, B had relative risk (RR) of 1.47 (95% CI 0.7-3) of receiving a mismatched unrelated donor (MMUD), RR of 2.34 (95% CI 1.2-4.4) of receiving a mismatched related donor (MMRD), and RR of 1.9 (95% CI 0.99-3.6) of receiving a mismatched cord blood donor (MMCBD) HCT, respectively. There was no significant difference in the incidence of aGVHD (48% W, 35% B), p = .1, or cGVHD (19% W, 28% B, p = .1), or primary cause of death. Overall 24-month survival was 61% (95% CI 55%-68%) for W, and 60% (95% CI 48-75) for B children, log-rank p = .7. While HLA matching improved survival in W children, the number of B children receiving HLA-matched HCT was too small to identify the impact of HLA matching on survival. CONCLUSIONS In this contemporary cohort of children with HM, we found that B children were more likely to receive HLA-MMD transplants, but this did not adversely affect survival or GVHD rates.

During the coronavirus 2019 pandemic we converted our liver transplant waitlist candidate education and support program to a virtual format and expanded it to include ongoing engagement sessions aimed to educate and empower patients to maximize opportunity for live donor liver transplantation. Over a period of 6 months from April 2020 to Sept 2020 we included 21 patients in this pilot quality improvement program. We collected data regarding patient response and potential donor referral activity. Overall, patient response was positive, and some patients saw progress toward live donor liver transplantation by fostering inquiry of potential live liver donors. Optimization of logistical aspects of the program including program flow, technology access, and utilization is required to enhance patient experience. Long-term follow-up is needed to assess impact on the outcome of transplantation rates. Future data collection and analysis should focus on assessment of any potential disparity that may result from utilization of virtual programming. Herein we provide a framework for this type of virtual program and describe our experience.