Improving Time to Antibiotic Administration for Pediatric Oncology Patients With New-Onset Fever.

PURPOSE: Time to antibiotic administration (TTA) in <60 minutes for children with neutropenic fever presenting to an emergency room is associated with reduced incidence of sepsis and intensive care admission. As such, TTA is used as a national quality metric for pediatric oncology patients. At our center, in 2020, 19% of the hospitalized patients with a new fever encounter were receiving antibiotics in <60 minutes, prompting a multidisciplinary approach to reach a goal of >90% in all pediatric patients with cancer with a new fever. METHODS: A multidisciplinary team completed four Plan-Do-Study-Act cycles between March 2021 and September 2023. We implemented education initiatives, an updated handoff smartphrase guiding the on-call team, an antibiotic champion (AC) nursing role, a revised fever plan for handoff, a rapid-response team to address new fevers, and an algorithm for blood culture collection. Data were collected, analyzed, and reported biweekly with feedback sought for delays in TTA. RESULTS: There was a total of 639 new fevers in 329 unique oncology patients. As of September 4, 2023, average TTA decreased from 89 minutes at baseline to 46.4 minutes for more than 12 months. The percentage of patients receiving first dose of antibiotic in <60 minutes also increased from 19% to 93.7%, which was sustained as well. The most effective interventions were creation of the AC role and streamlining the blood culture collection process. CONCLUSION: This project demonstrates the importance of multidisciplinary involvement for providing optimal care. Specific implementation of targeted education, an AC role, and development of an algorithm streamlining the processes led to meaningful targeted improvements. Further analyses will explore the impact of these interventions on patient outcomes.

KDS2010, a reversible MAO-B inhibitor, extends the lifetime of neural probes by preventing glial scar formation.

Implantable neural probes have been extensively utilized in the fields of neurocircuitry, systems neuroscience, and brain-computer interface. However, the long-term functionality of these devices is hampered by the formation of glial scar and astrogliosis at the surface of electrodes. In this study, we administered KDS2010, a recently developed reversible MAO-B inhibitor, to mice through ad libitum drinking in order to prevent glial scar formation and astrogliosis. The administration of KDS2010 allowed long-term recordings of neural signals with implantable devices, which remained stable over a period of 6 months and even restored diminished neural signals after probe implantation. KDS2010 effectively prevented the formation of glial scar, which consists of reactive astrocytes and activated microglia around the implant. Furthermore, it restored neural activity by disinhibiting astrocytic MAO-B dependent tonic GABA inhibition induced by astrogliosis. We suggest that the use of KDS2010 is a promising approach to prevent glial scar formation around the implant, thereby enabling long-term functionality of neural devices.

Current opinions on the management of prolonged ischemic priapism: does penoscrotal decompression outperform corporoglanular tunneling?

Prolonged ischemic priapism presents a treatment challenge given the difficulty in achieving detumescence and effects on sexual function. To evaluate current practice patterns, an open, web-based multi-institutional survey querying surgeons' experience with and perceived efficacy of tunneling maneuvers (corporoglanular tunneling and penoscrotal decompression), as well as impressions of erectile recovery, was administered to members of societies specializing in male genital surgery. Following distribution, 141 responses were received. Tunneling procedures were the favored first-line surgical intervention in the prolonged setting (99/139, 71.2% tunneling vs. 14/139, 10.1% implant, p < .001). Although respondents were more likely to have performed corporoglanular tunneling than penoscrotal decompression (124/138, 89.9% vs. 86/137, 62.8%, p < .001), penoscrotal decompression was perceived as more effective among those who had performed both (47.3% Very or Extremely Effective for penoscrotal decompression vs. 18.7% for corporoglanular tunneling; p < .001). Many respondents who had performed both tunneling procedures felt that most regained meaningful sexual function after either corporoglanular tunneling or penoscrotal decompression (33/75, 44.0% vs. 33/74, 44.6%, p = .942). While further patient-centered investigation is warranted, this study suggests that penoscrotal decompression may outperform corporoglanular tunneling for prolonged priapism, and that recovery of sexual function may be higher than previously thought after tunneling procedures.

Surgical Management of Male Stress Incontinence: Techniques, Indications, and Pearls for Success.

Purpose: Male stress urinary incontinence (SUI) has detrimental and long-lasting effects on patients. Management of this condition is an evolving field with multiple options for surgical treatment. We sought to review the pre-operative evaluation, intra-operative considerations, post-operative care, and future directions for treatment of male SUI. Methods: A literature review was performed using the PubMed platform to identify peer-reviewed, English-language articles published within the last 5 years pertaining to management of male stress urinary incontinence with an emphasis on devices currently on the market in the United States including the artificial urinary sphincter (AUS), male urethral slings, and the ProACTTM system. Patient selection criteria, success rates, and complications were compared between the studies. Results: Twenty articles were included in the final contemporary review. Pre-operative workup most commonly included demonstration of incontinence, PPD, and cystoscopy. Definition of success varied by study; the most common definition used was social continence (0-1 pads per day). Reported rates of success were higher for the AUS than for male urethral slings (73-93% vs 70-90%, respectively). Complications for these procedures include urinary retention, erosions, infections, and device malfunction. Newer treatment options including adjustable balloon systems and adjustable slings show promise but lack long-term follow-up. Conclusion: Patient selection remains the primary consideration for surgical decision-making for management of male SUI. The AUS continues to be the gold standard for moderate-to-severe male SUI but comes with inherent risk of need for revision. Male slings may be a superior option for appropriately selected men with mild incontinence but are inferior to the AUS for moderate and severe incontinence. Ongoing research will shed light on long-term results for newer options such as the ProACT and REMEEX systems.

Repurposing Atovaquone as a Therapeutic against Acute Myeloid Leukemia (AML): Combination with Conventional Chemotherapy Is Feasible and Well Tolerated.

Survival of pediatric AML remains poor despite maximized myelosuppressive therapy. The pneumocystis jiroveci pneumonia (PJP)-treating medication atovaquone (AQ) suppresses oxidative phosphorylation (OXPHOS) and reduces AML burden in patient-derived xenograft (PDX) mouse models, making it an ideal concomitant AML therapy. Poor palatability and limited product formulations have historically limited routine use of AQ in pediatric AML patients. Patients with de novo AML were enrolled at two hospitals. Daily AQ at established PJP dosing was combined with standard AML therapy, based on the Medical Research Council backbone. AQ compliance, adverse events (AEs), ease of administration score (scale: 1 (very difficult)-5 (very easy)) and blood/marrow pharmacokinetics (PK) were collected during Induction 1. Correlative studies assessed AQ-induced apoptosis and effects on OXPHOS. PDX models were treated with AQ. A total of 26 patients enrolled (ages 7.2 months-19.7 years, median 12 years); 24 were evaluable. A total of 14 (58%) and 19 (79%) evaluable patients achieved plasma concentrations above the known anti-leukemia concentration (>10 µM) by day 11 and at the end of Induction, respectively. Seven (29%) patients achieved adequate concentrations for PJP prophylaxis (>40 µM). Mean ease of administration score was 3.8. Correlative studies with AQ in patient samples demonstrated robust apoptosis, OXPHOS suppression, and prolonged survival in PDX models. Combining AQ with chemotherapy for AML appears feasible and safe in pediatric patients during Induction 1 and shows single-agent anti-leukemic effects in PDX models. AQ appears to be an ideal concomitant AML therapeutic but may require intra-patient dose adjustment to achieve concentrations sufficient for PJP prophylaxis.

Targeting Apoptosis in ALL.

PURPOSE OF REVIEW: While the treatment of acute lymphoblastic leukemia (ALL) has improved significantly over the last 30 years, the majority of adult patients will have their disease relapse. The BCL-2 gene was initially discovered from follicular lymphoma research; however, the BH3 family of proteins has is emerging to be crucial in patients with ALL due to their reliance on the balance of these pro-apoptotic and anti-apoptotic proteins in the BH3 family. We discuss apoptosis in ALL, the reliance mechanisms, drug development in this space, and areas for future research. RECENT FINDINGS: The first drugs that were developed to inhibit the BCL-2 pathway include both venetoclax (BCL-2 specific inhibitor) and navitoclax (BCL-2, BCL-XL, and BCL-W). These drugs show promise and have obtained complete remissions, minimal residual disease negative status, and have been used as a bridge to allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia and chronic lymphocytic leukemia. There are multiple ongoing clinical trials looking to assess the use of BCL-2 inhibition with chemotherapy, targeted therapies, and bi-specific T-cell engager therapies not only in both frontline and relapsed refractory ALL but also in consolidation and maintenance phases. There is still a large need for improvement of ALL outcomes in adult patients. Research has shown that ALL depends on the BCL-2 family of proteins for cell survival and proliferation. Targeting this pathway with BCL-2 inhibition has led to encouraging results, and future research is aimed at incorporating this targeted therapy into current treatment paradigms.

Four in one-Combination therapy using live Lactococcus lactis expressing three therapeutic proteins for the treatment of chronic non-healing wounds.

Diabetes mellitus is one of the major concerns for health care systems, affecting 382 million people worldwide. Among the different complications of diabetes, lower limbs chronic ulceration is a common, severe and costly cause of morbidity. Diabetic foot ulcers are a leading cause of hospitalization in diabetic patients and its rate exceed the ones of congestive heart failure, depression or renal disease. Diabetic non-healing ulcers account for more than 60% of all non-traumatic lower limb amputations and the five-year mortality after amputation is higher than 50%, being equal to several types of advanced cancer. The primary management goals for an existing diabetic foot ulcer are to achieve primary healing as expeditiously as possible and to achieve a reduction of the amputation rate in the patients. Unfortunately, approximately a quarter of patients do not partially or fully respond to the standard of care. Advanced therapies for chronic wounds are existing, however, recent guidelines including the latest reviews and meta-analyses of the scientific and clinical evidence available from current treatment strategies and new therapeutic agents revealed that there is a lack of clinical data and persistent gap of evidence for many of the advanced therapeutic approaches. In addition, no pharmacological wound healing product has gained authority approval for more than 10 years in both US and EU, constituting a highly unmet medical need. In this publication we present data from a live biopharmaceutical product AUP1602-C designed as a single pharmaceutical entity based on the non-pathogenic, food-grade lactic acid bacterium Lactococcus lactis subsp. cremoris that has been genetically engineered to produce human fibroblast growth factor 2,interleukin4 and colony stimulating factor 1. Designed to address different aspects of wound healing (i.e. fibroblast proliferation, angiogenesis and immune cell activation) and currently in phase I clinical study, we show how the combination of the individual components on the wound micro-environment initiates and improves the wound healing in chronic wounds.

Prison Culture as Rape Supportive: Applying Importation and Deprivation Models to Examine Inmate Beliefs.

While research examining sexual violence in prison has increased over the past 15 years, relatively scant attention has been paid to rape supportive beliefs and the factors influencing inmate adherence to these beliefs. Given the demonstrated role from studies outside the prison context that rape supportive beliefs have on sexual violence, important parallels can be drawn from studying the inmate population. Importation and deprivation models have been used to explain how inmates adapt to prison life-whether attitudes and behaviors are imported from their lives outside prison or are developed in prison due to the conditions of incarceration. Using a sample of male and female inmates (n = 875) from a large state prison system in the southern United States, the researchers explored the degree to which inmate rape supportive beliefs (IRSB) were influenced by variables indicative of importation or deprivation models of prison adaption. Findings revealed greater support for importation variables among both male and female inmates. With some variation, measures such as gender, age, ethnicity, and education were significant in explaining IRSB, similar to findings of studies on rape supportive beliefs among noninmate samples. Because these beliefs can manifest in problematic attitudes and behaviors among inmates, such as prison sexual violence and the underreporting of such violence, it is important that correctional administrators understand this relationship and take steps to lessen IRSB. Since IRSB largely correlate with factors unrelated to conditions of confinement, efforts to educate and sensitize inmates to prison sexual violence can replicate best practices based on populations outside of prisons.

Free energy and kinetics of cAMP permeation through connexin26 via applied voltage and milestoning.

The connexin family is a diverse group of highly regulated wide-pore channels permeable to biological signaling molecules. Despite the critical roles of connexins in mediating selective molecular signaling in health and disease, the basis of molecular permeation through these pores remains unclear. Here, we report the thermodynamics and kinetics of binding and transport of a second messenger, adenosine-3',5'-cyclophosphate (cAMP), through a connexin26 hemichannel (Cx26). First, inward and outward fluxes of cAMP molecules solvated in KCl solution were obtained from 4 µs of ± 200 mV simulations. These fluxes data yielded a single-channel permeability of cAMP and cAMP/K+ permeability ratio consistent with experimentally measured values. The results from voltage simulations were then compared with the potential of mean force (PMF) and the mean first passage times (MFPTs) of a single cAMP without voltage, obtained from a total of 16.5 µs of Voronoi-tessellated Markovian milestoning simulations. Both the voltage simulations and the milestoning simulations revealed two cAMP-binding sites, for which the binding constants KD and dissociation rates koff were computed from PMF and MFPTs. The protein dipole inside the pore produces an asymmetric PMF, reflected in unequal cAMP MFPTs in each direction once within the pore. The free energy profiles under opposite voltages were derived from the milestoning PMF and revealed the interplay between voltage and channel polarity on the total free energy. In addition, we show how these factors influence the cAMP dipole vector during permeation, and how cAMP affects the local and nonlocal pore diameter in a position-dependent manner.

Concepts, Practices, and Interactive Tutorial for Allosteric Network Analysis of Molecular Dynamics Simulations.

Over the past decade, concepts of network theory in combination with dynamical information from conformational ensembles have been widely applied to gain insights in understanding allosteric regulation in biomolecules. In this chapter, we introduce the basic theories and protocols used in protein dynamics network analysis through a series of interactive python Jupyter notebook scripts. While various network analysis methods exist in the literature, here we focus on the two popular methods based on correlated atomic motions and pairwise interaction energies. While the tutorial is based on a small prototypic protein, the workflow and protocol introduced here are optimized to handle large membrane proteins.

A Phase II Study of Durvalumab in Combination with Tremelimumab in Patients with Rare Cancers.

LESSONS LEARNED: Disease control with signals of response were demonstrated, which should lead to future validating clinical trials using checkpoint inhibitors in this underserved rare malignancy population. Although the study of single types of rare cancers is practically challenging, clinical trial designs that aggregate such patients into cohorts treated similarly are feasible, even in the community setting. BACKGROUND: Patients with rare cancers are an underserved population with limited access to clinical trials aside from phase I trials in the refractory setting. Treatment of these patients is often based on collections of anecdotes and small denominator review articles. Despite broad evidence of efficacy of combined immune checkpoint blockade across multiple tumor types, patients with rare tumors have not been afforded the opportunity for these therapies. METHODS: A phase II, investigator-initiated, single institution trial using durvalumab (1,500 mg every [Q]4 weeks × 13) and tremelimumab (75 mg Q4 weeks × 7, then Q12 weeks × 2) is reported. The population included 50 patients with advanced rare solid tumors (incidence <6/100,000 per year). The phase II dose and safety profile were defined in prior phase I trials. All patients had exhausted standard therapy options and all had received at least one prior line of systemic therapy (n = 49) unless a standard treatment option did not exist (n = 1). RESULTS: A complete response was demonstrated in one patient with anal cancer. Striking partial responses were seen in four patients. Prolonged disease stability was noted in 18 patients. Thirteen patients experienced disease progression. Patients were considered unevaluable if unable to initiate therapy (n = 6) or unable to complete two cycles of therapy (n = 8). In all cases, patients were unevaluable because of clinical deterioration. The toxicity profile paralleled prior published studies. Toxicities were manageable and without new signals. There were two events of grade 4 immune-mediated hepatitis and one death from pneumonitis. CONCLUSION: This single-cohort basket trial demonstrated clinical activity from combined checkpoint blockade in 23 of the 36 evaluable patients. Patients with rare cancers, not eligible for immunotherapy via conventional clinical trial mechanisms, should be considered for this therapy through compassionate use, further clinical trials, and national registry programs.

Ion Pairing and Dielectric Decrement in Glycosaminoglycan Brushes.

Cell-surface polysaccharides are essential to many aspects of physiology, serving as a highly conserved evolutionary feature of life and as an important part of the innate immune system in mammals. Here, as simplified biophysical models of these sugar coatings, we present results of molecular dynamics simulations of hyaluronic acid and heparin brushes that show important effects of ion pairing, water dielectric decrease, and coion exclusion. As in prior studies of macromolecular crowding under physiologically relevant salt concentrations, our results show equilibria with electroneutrality attained through screening and pairing of brush anionic charges by monovalent cations at the atomistic detail. Most surprising is the reversal of the Donnan potential obtained from both nonpolarizable and Drude polarizable force fields, in contrast to what would be expected based on electrostatic Boltzmann partitioning alone. Water dielectric decrement within the brush domain is also associated with Born hydration-driven cation exclusion from the brush. We observe that the primary partition energy attracting cations to attain brush electroneutrality is the ion pairing or salt-bridge energy. Potassium and sodium pairings to glycosaminoglycan carboxylates and sulfates show similar abundance of contact-pairing and solvent-separated pairing. We conclude that in these crowded macromolecular brushes, ion-pairing, Born-hydration, and electrostatic potential energies all contribute to attain electroneutrality and should therefore contribute in mean-field models to accurately represent brush electrostatics.

Crowding-induced opening of the mechanosensitive Piezo1 channel in silico.

Mechanosensitive Piezo1 channels are essential mechanotransduction proteins in eukaryotes. Their curved transmembrane domains, called arms, create a convex membrane deformation, or footprint, which is predicted to flatten in response to increased membrane tension. Here, using a hyperbolic tangent model, we show that, due to the intrinsic bending rigidity of the membrane, the overlap of neighboring Piezo1 footprints produces a flattening of the Piezo1 footprints and arms. Multiple all-atom molecular dynamics simulations of Piezo1 further reveal that this tension-independent flattening is accompanied by gating motions that open an activation gate in the pore. This open state recapitulates experimentally obtained ionic selectivity, unitary conductance, and mutant phenotypes. Tracking ion permeation along the open pore reveals the presence of intracellular and extracellular fenestrations acting as cation-selective sites. Simulations also reveal multiple potential binding sites for phosphatidylinositol 4,5-bisphosphate. We propose that the overlap of Piezo channel footprints may act as a cooperative mechanism to regulate channel activity.

Robotic Nephroureterectomy vs Laparoscopic Nephroureterectomy: Increased Utilization, Rates of Lymphadenectomy, Decreased Morbidity Robotically.

Introduction and Objective: Robotic radical nephroureterectomy (RRNU) may offer advantages over laparoscopic radical nephroureterectomy (LRNU). The purpose of this study is to evaluate the overall survival (OS) of patients with upper tract urothelial carcinoma (UTUC) who underwent RRNU vs LRNU and identify factors that account for differences. Methods: The National Cancer Database was queried from 2010 to 2016 for patients with American Joint Committee on Cancer 6th/7th edition Stage I/II/III UTUC. Kaplan-Meier analysis compared LRNU and RRNU OS. Univariate analysis detected differences between the groups. Cox regression determined factors associated with mortality rate. Logistic regression identified predictors of a lymph node dissection (LND) and 90-day mortality rate. Results: A total of 2631 patients met the criteria, 1129 of whom underwent RRNU and 1502 LRNU, with a follow-up of 33 and 35 months, respectively (p = 0.063). RRNU had a median OS of 71.1 vs 62.6 months (p = 0.033). LRNU patients were older (72.7 vs 71.4, p < 0.001) and had no differences in comorbidities, pathologic T stage, or grade. The LRNU cohort was less likely to undergo LND (19% vs 35%, p < 0.001) and had a lower median lymph node yield (3 vs 4, p < 0.001). LRNU patients more likely underwent conversion to an open procedure, had longer hospital stays, and higher 30- and 90-day mortality rates. LRNU was independently associated with mortality rate (p = 0.030). Age, grade, positive margins, pT/pN stage were associated with mortality rate. Younger age, RRNU, surgery at an academic center, and neoadjuvant chemotherapy predicted an LND. Conclusions: RRNU demonstrated increased rates of LND and may offer a short-term morbidity benefit to LRNU. Survival differences may be due to improved characterization of disease through LND.

Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19.

OBJECTIVES: Cytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients. METHODS: Five single volume plasma exchanges over eight days within a 14-day study period. In mechanically ventilated patients, oxygenation was measured via the PaO2/FiO2 (P/F) ratio and the oxygenation index (OI) daily for 14 days. Supplemental oxygen requirements were tracked daily for non-ventilated patients. RESULTS: Non-ventilated patients were liberated from supplemental oxygen after TPE. The response was rapid with an 87% average reduction in oxygenation requirements following and average time to return to room air of 5.25 days. All mechanically ventilated patients demonstrated improvement in oxygenation with a 78% average improvement in the P/F ratio and a 43% improvement in OI. C-reactive protein (CRP) and serum levels of IL-6, IL-8, IL-10, TNFα, IFNγ and GM-CSF, were measured daily with immediate post TPE levels drawn on days 1, 2, 4, 6 and 8. All patients demonstrated significant reductions in CRP, IL-6, IL-10 and TNFα. CONCLUSIONS: In the majority of patients with Penn class 3 and 4 CRS complicating COVID-19, TPE demonstrated a prompt improvement in oxygenation and reduction in cytokine load without compromising patient safety. As this pilot study was envisioned to be hypothesis generating, expanded trials using TPE alone and in conjunction with novel pharmacologic agents are warranted. REGISTRATION: ClinicalTrials.gov NCT04374149.

In silico prediction of ARB resistance: A first step in creating personalized ARB therapy.

Angiotensin II type 1 receptor (AT1R) blockers (ARBs) are among the most prescribed drugs. However, ARB effectiveness varies widely, which may be due to non-synonymous single nucleotide polymorphisms (nsSNPs) within the AT1R gene. The AT1R coding sequence contains over 100 nsSNPs; therefore, this study embarked on determining which nsSNPs may abrogate the binding of selective ARBs. The crystal structure of olmesartan-bound human AT1R (PDB:4ZUD) served as a template to create an inactive apo-AT1R via molecular dynamics simulation (n = 3). All simulations resulted in a water accessible ligand-binding pocket that lacked sodium ions. The model remained inactive displaying little movement in the receptor core; however, helix 8 showed considerable flexibility. A single frame representing the average stable AT1R was used as a template to dock Olmesartan via AutoDock 4.2, MOE, and AutoDock Vina to obtain predicted binding poses and mean Boltzmann weighted average affinity. The docking results did not match the known pose and affinity of Olmesartan. Thus, an optimization protocol was initiated using AutoDock 4.2 that provided more accurate poses and affinity for Olmesartan (n = 6). Atomic models of 103 of the known human AT1R polymorphisms were constructed using the molecular dynamics equilibrated apo-AT1R. Each of the eight ARBs was then docked, using ARB-optimized parameters, to each polymorphic AT1R (n = 6). Although each nsSNP has a negligible effect on the global AT1R structure, most nsSNPs drastically alter a sub-set of ARBs affinity to the AT1R. Alterations within N298 -L314 strongly effected predicted ARB affinity, which aligns with early mutagenesis studies. The current study demonstrates the potential of utilizing in silico approaches towards personalized ARB therapy. The results presented here will guide further biochemical studies and refinement of the model to increase the accuracy of the prediction of ARB resistance in order to increase overall ARB effectiveness.

Women with a substance use disorder: Treatment completion, pregnancy, and compulsory treatment.

Over the last several decades, research regarding substance use treatment programs has focused on the unique and differential outcomes of male and female illicit substance users. Research less frequently examines the unique individual and contextual factors that may influence treatment outcomes. One such population that merits special consideration is pregnant women, as substance use within this population has deleterious effects for both the women and their unborn children. The current study employs propensity score matching to determine if pregnancy and referral source to treatment affect treatment program outcomes. Findings suggest that pregnant women, compared to similarly situated nonpregnant women, are significantly less likely to complete substance use treatment; however, pregnant women who were referred to treatment by the criminal justice system were significantly more likely to complete treatment than those who entered treatment by other referral sources.

Evaluation of Chest Radiographs of Children with Newly Diagnosed Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the diagnostic yield of baseline chest radiographs (CXRs) of children with acute lymphoblastic leukemia (ALL). STUDY DESIGN: We reviewed the CXR findings at diagnosis for 990 patients aged 1-18 years with ALL treated during the Total XV and XVI studies at St. Jude Children's Research Hospital and evaluated the associations of these findings with clinical characteristics and initial management. RESULTS: Common findings were peribronchial/perihilar thickening (n = 187 [19.0%]), pulmonary opacity/infiltrate (n = 159 [16.1%]), pleural effusion/thickening (n = 109 [11.1%]), mediastinal mass (n = 107 [10.9%]), and cardiomegaly (n = 68 [6.9%]). Portable CXRs provided results comparable with those obtained with 2-view films. Forty of 107 patients with a mediastinal mass (37.4%) had tracheal deviation/compression. Mediastinal mass, pleural effusion/thickening, and tracheal deviation/compression were more often associated with T-cell ALL than with B-cell ALL (P < .001 for all). Pulmonary opacity/infiltrate was associated with younger age (P = .003) and was more common in T-cell ALL than in B-cell ALL (P = .001). Peribronchial/perihilar thickening was associated with younger age (P < .001) and with positive central nervous system disease (P = .012). Patients with cardiomegaly were younger (P = .031), more often black than white (P = .007), and more often categorized as low risk than standard/high risk (P = .017). Patients with a mediastinal mass, pleural effusion/thickening, tracheal deviation/compression, or pulmonary opacity/infiltrate were more likely to receive less invasive sedation and more intensive care unit admissions and respiratory support (P ≤ .001 for all). Cardiomegaly was associated with intensive care unit admission (P = .008). No patients died of cardiorespiratory events during the initial 7 days of management. CONCLUSIONS: The CXR can detect various intrathoracic lesions and is helpful in planning initial management.