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RATIONALE: Little is known about the consequences of intensivists' work schedules, or intensivist continuity of care. OBJECTIVES: To assess the impact of weekend respite for intensivists, with consequent reduction in continuity of care, on them and their patients. METHODS: In five medical intensive care units (ICUs) in four academic hospitals we performed a prospective, cluster-randomized, alternating trial of two intensivist staffing schedules. Daily coverage by a single intensivist in half-month rotations (continuous schedule) was compared with weekday coverage by a single intensivist, with weekend cross-coverage by colleagues (interrupted schedule). We studied consecutive patients admitted to study units, and the intensivists working in four of the participating units. MEASUREMENTS AND MAIN RESULTS: The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates. The primary intensivist outcome was physician burnout. Analysis was by multivariable regression. A total of 45 intensivists and 1,900 patients participated in the study. Continuity of care differed between schedules (patients with multiple intensivists = 28% under continuous schedule vs. 62% under interrupted scheduling; P < 0.0001). LOS and mortality were nonsignificantly higher under continuous scheduling ([Delta]ICU LOS 0.36 d, P = 0.20; [Delta]hospital LOS 0.34 d, P = 0.71; ICU mortality, odds ratio = 1.43, P = 0.12; hospital mortality, odds ratio = 1.17,P = 0.41). Intensivists experienced significantly higher burnout, work-home life imbalance, and job distress working under the continuous schedule. CONCLUSIONS: Work schedules where intensivists received weekend breaks were better for the physicians and, despite lower continuity of intensivist care, did not worsen outcomes for medical ICU patients. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between body mass index (BMI) and hospital mortality for critically ill adults.Design: Retrospective cohort study.Setting: One-hundred six intensive care units (ICUs) in 84 hospitals.Patients: Mechanically ventilated adults (n=1,488) with acute lung injury (ALI) included in the Project IMPACT database between December 1995 and September 2001.Interventions: None.Measurements and Main Results: Over half of the cohort had a BMI above the normal range. Unadjusted analyses showed that BMI was higher among subjects who survived to hospital discharge vs. those who did not (p<.0001). ICU and hospital mortality rates were lower in higher BMI categories. After risk-adjustment, BMI was independently associated with hospital mortality (p<.0001) when modeled as a continuous variable. The adjusted odds were highest at the lowest BMIs and then declined to a minimum between 35 and 40 kg/m2. Odds increased after the nadir but remained below those seen at low BMIs. With use of a categorical designation, BMI was also independently associated with hospital mortality (p=.0055). The adjusted odds were highest for the underweight BMI group (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.05-3.60) relative to the normal BMI group. As in the analysis using the continuous BMI variable, the odds of hospital mortality were decreased for the groups with higher BMIs (overweight adjusted OR, 0.72; 95% CI, 0.51-1.02; obese adjusted OR, 0.67; 95% CI, 0.46-0.97; severely obese adjusted OR, 0.78; 95% CI, 0.44-1.38). Differences in the use of heparin prophylaxis mediated some of the protective effect of severe obesity.Conclusions: BMI was associated with risk-adjusted hospital mortality among mechanically ventilated adults with ALI. Lower BMIs were associated with higher odds of death, whereas overweight and obese BMIs were associated with lower odds. [ABSTRACT FROM AUTHOR]

Pyoderma gangrenosum (PG) can be difficult to diagnose, leading to diagnostic delay which affects patient outcomes and increases health care utilization. Among different scenarios of diagnostic delay, atypical infections can mimic PG. Here, we present a case of extensive cutaneous leishmaniasis initially misdiagnosed as the superficial granulomatous variant of PG and describe diagnostic clues to aid in differentiation., (© 2024 Australasian College of Dermatologists.)

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium., Methods: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders., Results: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes., Conclusion: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

The atomistic structure of lithium nickelate (LiNiO 2 ), the parent compound of Ni-rich layered oxide cathodes for Li-ion batteries, continues to elude a comprehensive understanding. The common consensus is that the material exhibits local Jahn-Teller distortions that dynamically reorient, resulting in a time-averaged undistorted R 3̅ m structure. Through a combination of ab initio molecular dynamics (AIMD) simulations and variable-temperature X-ray diffraction (VT-XRD), we explore Jahn-Teller distortions in LiNiO 2 as a function of temperature. Static Jahn-Teller distortions are observed at low temperatures ( T < 250 K) via AIMD simulations, followed by a broad phase transition that occurs between 250 and 350 K, leading to a highly dynamic, displacive phase at high temperatures ( T > 350 K), which does not show the four short and two long bonds characteristic of local Jahn-Teller distortions. These transitions are followed in the AIMD simulations via abrupt changes in the calculated pair distribution function and the bond-length distortion index and in X-ray diffraction via the monoclinic lattice parameter ratio, a mon / b mon , and δ angle, the fit quality of an R 3̅ m -based structural refinement, and a peak sharpening of the diffraction peaks on heating, consistent with the loss of distorted domains. Between 250 and 350 K, a mixed-phase regime is found via the AIMD simulations where distorted and undistorted domains coexist. The repeated change between the distorted and undistorted states in this mixed-phase regime allows the Jahn-Teller long axes to change direction. These pseudorotations of the Ni-O long axes are a side effect of the onset of the displacive phase transition. Antisite defects, involving Li ions in the Ni layer and Ni ions in the Li layer, are found to pin the undistorted domains at low temperatures, impeding cooperative ordering at a longer length scale., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data., Methods: Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models., Results: Among 312 879 children with a median follow-up of 13.6 years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes., Conclusions: Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling., Objective: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB., Methods: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal., Results: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%)., Limitations: Retrospective design., Conclusions: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis., Competing Interests: Conflicts of interest Dr Bruckner serves as an investigator for Fibrocell, Phoenix Tissue Repair, PROQR/Wings, and Castle Creek and on an ad hoc advisory board for Castle Creek. Dr Pope receives research funding from the EB Research Foundation. Dr Paller serves as an investigator for Castle Creek and Lenus Pharmaceuticals and has been a consultant with honorarium for Abeona. Dr Levy serves on the advisory board for Cassiopea, Regeneron; as an investigator for Fibrocell/Castle Creek, Galderma, Janssen, Pfizer; on the Data Safety and Monitoring Board for Novan; and as a section editor for UpToDate. Dr Lucky serves as an investigator for Lenus Pharmaceuticals and Castle Creek and on the scientific advisory board for EBRP (EB Research Partnership) and Abeona. Dr Glick serves as an investigator for Lenus Pharmaceuticals. Authors Phillips, Augsburger, and Peoples and Drs Huang, Kaplan, Khuu, Tang, Lara-Corrales, Wiss, Levin, Morel, Hook, Eichenfield, McCuaig, Powell, Castelo-Soccio, Price, Schachner, Browning, Jahnke, Shwayder, and Bayliss have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Hydrocephalus is the most common neurosurgical disorder in children, and cerebrospinal fluid (CSF) diversion with shunt placement is the most commonly performed pediatric neurosurgical procedure. CT is frequently used to evaluate children with suspected CSF shunt malfunction to assess change in ventricular size. Moreover, careful review of the CT images is important to confirm the integrity of the imaged portions of the shunt system. Subtle shunt disruptions can be missed on multiplanar two-dimensional (2-D) CT images, especially when the disruption lies in the plane of imaging. The use of volume-rendered CT images enables radiologists to view the extracranial shunt tubing within the field of view as a three-dimensional (3-D) object. This allows for a rapid and intuitive method of assessing the integrity of the extracranial shunt tubing. The purpose of this pictorial essay is to discuss how volume-rendered CT images can be generated to evaluate CSF shunts in the pediatric population and to provide several examples of their utility in diagnosing shunt disruption. We also address the potential pitfalls of this technique and ways to avoid them., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness., Research Question: What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries?, Study Design and Methods: Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay., Results: We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P < .001). In stringent match, 107,016 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (22.22% vs 26.28%, respectively), yielding an ARR of 4.06% (95% CI, 3.70-4.41; P < .001). At the subject level, our HGLM found compliance associated with lower 30-day risk-adjusted mortality (adjusted conditional OR, 0.829; 95% CI, 0.812-0.846; P < .001). Multiple elements correlated with lower mortality. Median length of stay was shorter among cases whose care was compliant (5 vs 6 days; interquartile range, 3-9 vs 4-10, respectively; P < .001)., Interpretation: Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

Pediatric bowel obstructions are one of the most common surgical emergencies in children, and imaging plays a vital role in the evaluation and diagnosis. An evidence-based and practical imaging approach to diagnosing and localizing pediatric bowel obstructions is essential for optimal pediatric patient care. This article discusses an up-to-date practical diagnostic imaging algorithm for pediatric bowel obstructions and presents the imaging spectrum of pediatric bowel obstructions and their underlying causes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pediatric abdominal masses are commonly encountered in the pediatric population, with a broad differential diagnosis that encompasses benign and malignant entities. The primary role of abdominal imaging in the setting of a suspected pediatric abdominal mass is to establish its presence, as nonneoplastic entities can mimic an abdominal mass, and to identify characteristic imaging features that narrow the differential diagnosis. In the setting of a neoplasm, various imaging modalities play an important role to characterize the mass, stage extent of disease, and assist in presurgical planning. The purpose of this article is to discuss a practical imaging algorithm for suspected pediatric abdominal masses and to describe typical radiological findings of the commonly encountered abdominal masses in neonates and children with emphasis on imaging guidelines and recommendations., Competing Interests: Disclosures The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The incidence of dermatologic infections in patients receiving checkpoint inhibitors (CPIs) has not been systematically described., Objective: Identify the incidence of dermatologic infections in patients who received CPIs., Methods: Retrospective review of dermatologic infections in patients who received CPIs between 2005 and 2020 and were evaluated by dermatologists at Memorial Sloan Kettering Cancer Center., Results: Of 2061 patients in the study, 1292 were actively receiving CPIs (≤ 90 days since the last dose) and 769 had previously been on CPIs (> 90 days since the last dose). The dermatologic infection rate was significantly higher in patients with active CPI treatment (17.5%) than in patients not actively being treated (8.2%; P < .0001). In patients on CPIs, 82 (36.2%), 78 (34.5%), and 48 (21.2%) had bacterial, fungal, and viral infections, respectively, and 18 (8.0%) had polymicrobial infections. Anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy was associated with the highest risk of infection (hazard ratio, 2.93; 95% confidence interval, 1.87 to 4.60; P < .001)., Limitations: Retrospective design and sample limited to patients referred to dermatology., Conclusions: Patients actively receiving CPIs are more susceptible to dermatologic infections, with anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy carrying the highest risk, suggesting that the index of suspicion for infections should be increased in these patients to minimize morbidity and optimize care., Competing Interests: Conflicts of interest Dr Postow received consulting fees from 2015 to the present from BMS, Merck, Array BioPharma, Novartis, Incyte, NewLink Genetics, Aduro; honoraria from BMS and Merck; and institutional support from RGenix, Infinity, BMS, Merck, Array BioPharma, Novartis, and AstraZeneca. Dr Warner is a consultant for Nanobiotix, Inc; participates on the Scientific Advisory Board for Iovance, Inc; and receives an honorarium from LG Chem Life Sciences, Inc. Dr Rosenberg receives consulting fees and trial funding from Bayer, Seattle Genetics, AstraZeneca, Roche/Genentech, Astellas, and QED Therapeutics; consulting fees from BMS, Merck, Pfizer, Pharmacyclics, Boehringer Ingelheim, GSK, Janssen, Lilly, and Mirati; and an honorarium from Chugai. Dr Noor participates on the Advisory Board of Kyowa Kirin and is a speaker for Array BioPharma. Dr Markova participates on the Advisory Board for AstraZeneca Pharmaceuticals LP and receives research funding from Incyte. Dr Lacouture is a consultant and speaker for Johnson and Johnson, Novocure Inc, Janssen Research & Development LLC, Novartis Pharmaceuticals Corporation, F. Hoffmann-La Roche AG, AstraZeneca Pharmaceuticals LP, Genentech Inc, Seattle Genetics, Lutris, Paxman Coolers, OnQuality Pharmaceuticals Ltd, Novartis and receives research funding from Berg, Bristol-Myers Squibb, Lutris, Paxman, Novocure, US Biotest, and Veloce. Drs Do, Barrios, and Phillips have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Respiratory variation in carotid artery peak systolic velocity (ΔVpeak) assessed by point-of-care ultrasound (POCUS) has been proposed as a noninvasive means to predict fluid responsiveness. We aimed to evaluate the ability of carotid ΔVpeak as assessed by novice physician sonologists to predict fluid responsiveness., Methods: This study was conducted in 2 intensive care units. Spontaneously breathing, nonintubated patients with signs of volume depletion were included. Patients with atrial fibrillation/flutter, cardiogenic, obstructive or neurogenic shock, or those for whom further intravenous (IV) fluid administration would be harmful were excluded. Three novice physician sonologists were trained in POCUS assessment of carotid ΔVpeak. They assessed the carotid ΔVpeak in study participants prior to the administration of a 500 mL IV fluid bolus. Fluid responsiveness was defined as a ≥10% increase in cardiac index as measured using bioreactance., Results: Eighty-six participants were enrolled, 50 (58.1%) were fluid responders. Carotid ΔVpeak performed poorly at predicting fluid responsiveness. Test characteristics for the optimum carotid ΔVpeak of 8.0% were: area under the receiver operating curve = 0.61 (95% CI: 0.48-0.73), sensitivity = 72.0% (95% CI: 58.3-82.56), specificity = 50.0% (95% CI: 34.5-65.5)., Conclusions: Novice physician sonologists using POCUS are unable to predict fluid responsiveness using carotid ΔVpeak. Until further research identifies key limiting factors, clinicians should use caution directing IV fluid resuscitation using carotid ΔVpeak.

Background: Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents., Patients and Methods: Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0., Results: A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab., Conclusions: IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies., Competing Interests: Disclosure AM has an advisory board role in AstraZeneca, receives research funding from Incyte, and is supported by a Dermatology Foundation Career Development Award. EQ receives royalties from UpToDate. SAF receives research funding from AstraZeneca and Genentech/Roche, has a consulting/advisory relationship with Merck, and has ownership interests in Urogen, Allogene Therapeutics, Neogene Therapeutics, Kronos Bio, InconOVir and Vida Ventures. MHV reports receiving commercial research support from Pfizer and honoraria from Pfizer, Exelixis, Eisai, Calithera Biosciences, and Corvus Pharmaceuticals. AD discloses honoraria/advisory board participation for Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millennium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, Beigene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, and MORE Health; associated research funding paid to the institution from Pfizer, Exelixis, GlaxoSmithKline, Teva, Taiho, and PharmaMar; research for Foundation Medicine; royalties from Wolters Kluwer; expenses from Merck and Puma; and CME honoraria from Medscape, OncLive, PeerVoice, Physicians Education Resources, Targeted Oncology, and Research to Practice. MDH receives research funding from Bristol Myers Squibb; is a paid consultant to Merck, Bristol Myers Squibb, AstraZeneca, Genentech/Roche, Nektar, Syndax, Mirati, Blueprint, Achilles Therapeutics, PACT Pharma, Immunai, and Shattuck Labs; receives travel support/honoraria from AstraZeneca, Eli Lilly, Merck, and BMS; and a patent has been filed by MSK related to the use of tumor mutation burden to predict response to immunotherapy (PCT/US2015/062208), which has received licensing fees from PGDx. EAC reports consultancy fees from Pfizer, Novartis, Bristol Myers Squibb, COTA, Genentech-Roche, and Heron Therapeutics. DYML has been a consultant for Genentech and Novartis. MEL has a consultant role with Johnson and Johnson, Novocure, QED, Bicara, Janssen, Novartis, F. Hoffmann-La Roche AG, EMD Serono, Astrazeneca, Innovaderm, Deciphera, DFB, Azitra, Kintara, RBC/La Roche Posay, Trifecta, Varsona, Genentech, Loxo, Seattle Genetics, Lutris, OnQuality, Azitra, Roche, NCODA, Apricity, Oncoderm Labs, Hoth Therapeutics. Dr. Lacouture also receives research funding from Lutris, Paxman, Novocure, J&J, US Biotest, OQL, Novartis and AZ. All other authors have declared no conflicts of interest., (Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)

OBJECTIVE. Intussusception is the most common cause of intestinal obstruction in young children. Radiology has a key role in its diagnosis and treatment. This systematic review summarizes the currently available evidence for best practices in radiologic management of pediatric intussusception. CONCLUSION. High diagnostic accuracy and lack of ionizing radiation make ultrasound (US) the preferred imaging modality for diagnosing intussusception. For intussusception reduction, fluoroscopy-guided pneumatic enema and US-guided hydrostatic enema are equally dependable and safe techniques. The areas that warrant further research in this field include the efficacy and safety of the US-guided pneumatic enema, potential benefits of sedation and general anesthesia for the reduction procedure, and the optimal management of intussusceptions potentially involving pathologic lead points.

As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D 3 analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Measurement of carotid blood flow (CBF) and corrected carotid flow time (ccFT) has been proposed as a non-invasive means of determining fluid responsiveness. We evaluated the ability of CBF and ccFT as assessed by novice sonologists to determine fluid responsiveness in intensive care unit patients. Three novice physician sonologists performed carotid ultrasounds before and after a fluid bolus and calculated changes in CBF and ccFT. Fluid responsiveness was defined as a ≥10% increase in cardiac index as measured using bioreactance. Of 112 participants, 56 (50%) were fluid responders. Changes in CBF and ccFT performed poorly at determining fluid responsiveness: 19 mL/min (area under the receiver operating characteristic curve: 0.58, 95% confidence interval: 0.47-0.68) and 6 ms (0.59, 0.46-0.65) respectively. Novice physician sonologists are unable to determine fluid responsiveness using CBF or ccFT. Further research is needed to identify the key limiting factors in using carotid ultrasound to determine fluid responsiveness., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: Cochlear implant depth of insertion affects audiologic outcomes and can be measured in adults using plain films obtained in the "cochlear view." The objective of this study was to assess interrater and intrarater reliability of measuring depth of insertion using cochlear view radiography., Study Design: Prospective, observational., Setting: Tertiary referral pediatric hospital., Subjects and Methods: Patients aged 11 months to 20 years (median, 4 years; interquartile range [IQR], 1-8 years) undergoing cochlear implantation at our institution were studied over 1 year. Children underwent cochlear view imaging on postoperative day 1. Films were deidentified and 1 image per ear was selected. Two cochlear implant surgeons and 2 radiologists evaluated each image and determined angular depth of insertion. Images were re-reviewed 6 weeks later by all raters. Inter- and intrarater reliability were calculated with intraclass correlation coefficients (ICCs)., Results: Fifty-seven ears were imaged from 42 children. Forty-nine ears (86%) had successful cochlear view x-rays. Median angular depth of insertion was 381° (minimum, 272°; maximum, 450°; IQR, 360°-395°) during the first round of measurement. Measurements of the same images reviewed 6 weeks later showed median depth of insertion of 382° (minimum, 272°; maximum, 449°; IQR, 360°-397°). Interrater and intrarater reliability ICCs ranged between 0.81 and 0.96, indicating excellent reliability., Conclusions: Postoperative cochlear view radiography is a reliable tool for measurement of cochlear implant depth of insertion in infants and children. Further studies are needed to determine reliability of intraoperatively obtained cochlear view radiographs in this population.

Importance: Persistent radiation-induced alopecia (pRIA) and its management have not been systematically described., Objective: To characterize pRIA in patients with primary central nervous system (CNS) tumors or head and neck sarcoma., Design, Setting, and Participants: A retrospective cohort study of patients from January 1, 2011, to January 30, 2019, was conducted at 2 large tertiary care hospitals and comprehensive cancer centers. Seventy-one children and adults diagnosed with primary CNS tumors or head and neck sarcomas were evaluated for pRIA., Main Outcomes and Measures: The clinical and trichoscopic features, scalp radiation dose-response relationship, and response to topical minoxidil were assessed using standardized clinical photographs of the scalp, trichoscopic images, and radiotherapy treatment plans., Results: Of the 71 patients included (median [range] age, 27 [4-75] years; 51 female [72%]), 64 (90%) had a CNS tumor and 7 (10%) had head and neck sarcoma. Alopecia severity was grade 1 in 40 of 70 patients (56%), with localized (29 of 54 [54%]), diffuse (13 of 54 [24%]), or mixed (12 of 54 [22%]) patterns. The median (range) estimated scalp radiation dose was 39.6 (15.1-50.0) Gy; higher dose (odds ratio [OR], 1.15; 95% CI, 1.04-1.28) and proton irradiation (OR, 5.7; 95% CI, 1.05-30.8) were associated with greater alopecia severity (P < .001), and the dose at which 50% of patients were estimated to have severe (grade 2) alopecia was 36.1 Gy (95% CI, 33.7-39.6 Gy). Predominant trichoscopic features included white patches (16 of 28 [57%]); in 15 patients, hair-shaft caliber negatively correlated with scalp dose (correlation coefficient, -0.624; P = .01). The association between hair density and scalp radiation dose was not statistically significant (-0.381; P = .16). Twenty-eight of 34 patients (82%) responded to topical minoxidil, 5% (median follow-up, 61 [interquartile range, 21-105] weeks); 4 of 25 (16%) topical minoxidil recipients with clinical images improved in severity grade. Two patients responded to hair transplantation and 1 patient responded to plastic surgical reconstruction., Conclusions and Relevance: Persistent radiation-induced alopecia among patients with primary CNS tumors or head and neck sarcomas represents a dose-dependent phenomenon that has distinctive clinical and trichoscopic features. The findings of this study suggest that topical minoxidil and procedural interventions may have benefit in the treatment of pRIA.

OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.

Understanding of coronavirus disease 2019 is rapidly evolving with new articles on the subject daily. This flood of articles can be overwhelming for busy practicing clinicians looking for key pieces of information that can be applied in daily practice. This review article synthesizes the reported imaging findings in pediatric Coronavirus disease 2019 (COVID-19) across the literature, offers imaging differential diagnostic considerations and useful radiographic features to help differentiate these entities from COVID-19, and provides recommendations for requesting imaging studies to evaluate suspected cases of pediatric COVID-19., (© 2020 Wiley Periodicals LLC.)

Background: Dermatologic adverse events (dAEs) of anticancer therapies may negatively impact dosing and quality of life. While therapy interruption patterns due to dAEs have been studied in hospitalized cancer patients, similar outcomes in outpatient oncodermatology are lacking., Objectives: To analyse the therapy interruption patterns, clinico-histopathologic characteristics and management outcomes of outpatient dermatology consultations for acute dAEs attributed to the most frequently interrupted class of oncologic agents., Methods: We performed a retrospective cohort study of all cancer patients who received a same-day outpatient dermatology consultation for acute dAEs at our institution from 1 January to 30 June 2015. Relevant data were abstracted from electronic medical records, including demographics, oncologic history and explicit recommendations by both the referring clinician and consulting dermatologist on anticancer therapy interruption. Consultations with the most frequently interrupted class of oncologic treatment were characterized according to clinico-histopathologic features, dermatologic management and clinical outcomes., Results: There were 426 same-day outpatient dermatology consultations (median age 59, 60% female, 30% breast cancer), of which 295 (69%) had systemic anticancer therapy administered within 30 days prior. There was weak inter-rater agreement between referring clinicians and consulting dermatologists on interruption of anticancer treatment (n = 150, κ = 0.096; 95% CI -0.02 to 0.21). Seventy-three (25%) consultations involved interruption by the referring clinician, most commonly targeted therapy (24, 33%). Maculopapular rash was commonly observed in 23 consultations with 25 dAEs attributed to targeted agents (48%), and topical corticosteroids were most frequently utilized for management (22, 38%). The majority (83%) of consultations with targeted therapy-induced dAEs responded to dermatologic treatment and 84% resumed oncologic therapy, although three (19%) at a reduced dose. Rash recurred only in two instances (13%)., Conclusions: A high frequency of positive outcomes in the management of targeted therapy-induced dAEs by outpatient consulting dermatologists and low recurrence of skin toxicity suggests impactful reductions in interruption of anticancer therapy., (© 2019 European Academy of Dermatology and Venereology.)

End-stage organ failure is commonly treated with transplantation of the respective failing organ. Although outcomes have progressively improved over the decades, early and late complications do occur, and are often diagnosed by imaging. Given the increasing survival rates of transplant patients, the general radiologist may encounter these patients in the outpatient setting. Awareness of the normal radiologic findings after transplantation, and imaging findings of the more common complications, is therefore important. We review and illustrate the imaging assessment of complications from lung, liver, and renal transplantation, highlighting the key similarities and differences between pediatric and adult patients., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Hematopoietic stem cell transplantation is an intravenous transfusion of pluripotent stem cells to repopulate the marrow and restore immunocompetence. However, before transplantation, the patient undergoes a conditioning regimen to eradicate the underlying disease, subsequently resulting in an immunocompromised state. Serious and some life-threatening complications involving any organ can occur. Currently, with advances in hematopoietic stem cell transplantation techniques and posttransplant management, more pediatric patients are now living longer and into their adulthood. The goal of this review article is to discuss the common neurologic, pulmonary, and abdominal complications associated with hematopoietic stem cell transplantation with emphasis on their imaging characteristics., Competing Interests: Disclosure E.Y. Lee received traveling and honorarium support from the Guebert Group as an invited speaker at an international meeting (AOSPR). The other authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

OBJECTIVE. Dual-energy CT is gaining increasing recognition as a valuable diagnostic tool for assessing abdominal neoplasms. Nevertheless, much of the literature has focused on its use in adults. This review article illustrates specific tools available with dual-energy CT in the evaluation of pediatric abdominal neoplasms. Additionally, common imaging artifacts and pitfalls in dual-energy CT of the pediatric abdomen are outlined. CONCLUSION. Dual-energy CT can augment diagnostic yield in the imaging evaluation of pediatric abdominal neoplasms.

Coronavirus disease 2019 (COVID-19) has quickly spread since it was first detected in December 2019 and has evolved into a global pandemic with over 1.7 million confirmed cases in over 200 countries around the world at the time this document is being prepared. Owing to the novel nature of the virus and the rapidly evolving understanding of the disease, there is a great deal of uncertainty surrounding the diagnosis and management of COVID-19 pneumonia in pediatric patients. Chest imaging plays an important role in the evaluation of pediatric patients with COVID-19; however, there is currently little information available describing imaging manifestations of COVID-19 in pediatric patients and even less information discussing the utilization of imaging studies in pediatric patients. To specifically address these concerns, a group of international experts in pediatric thoracic imaging from five continents convened to create a consensus statement describing the imaging manifestations of COVID-19 in the pediatric population, discussing the potential utility of structured reporting during the COVID-19 pandemic, and generating consensus recommendations for utilization of chest radiographs and CT in the evaluation of pediatric patients with COVID-19. The results were compiled into two structured reporting algorithms (one for chest radiographs and one for chest CT) and eight consensus recommendations for the utilization of chest imaging in pediatric COVID-19 infection. © RSNA, 2020., Competing Interests: Disclosures of Conflicts of Interest: A.M.F. disclosed no relevant relationships. G.S.P. disclosed no relevant relationships. W.C.C. disclosed no relevant relationships. P.D. disclosed no relevant relationships. K.M.D. disclosed no relevant relationships. P.G.P. disclosed no relevant relationships. T.K. disclosed no relevant relationships. A.J.W. disclosed no relevant relationships. E.Y.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: Guerbet supported author’s traveling and accommodation to 2019 AOSPR meeting in Seoul, Korea for luncheon lecture of contrast agent for pediatric imaging study; author paid by Michigan Professional Insurance Exchange for medical legal consultation work ($3529.17); author receives royalties for editorial work for textbook publication from Wolters Kluwer Health (book royalty = $1008.55) and Elsevier (book royalty = $1000). Other relationships: disclosed no relevant relationships., (2020 by the Radiological Society of North America, Inc.)

Background: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan., Methods: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable., Results: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups., Conclusions: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis.

Purpose: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics., Methods: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed., Results: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype ( P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043)., Conclusion: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Computed tomography (CT) is the imaging modality of choice for evaluating mediastinal masses detected by radiography or clinical presentation. However, CT results can often be indeterminate. Thoracic magnetic resonance (MR) imaging is a noninvasive way to characterize mediastinal lesions, site of origin, and involvement of adjacent structures by providing higher soft tissue contrast than CT, with superior tissue characterization and higher diagnostic specificity. Thoracic MR imaging of mediastinal masses can increase diagnostic certainty, reduce the number of surgical interventions, and improve clinical decision making. In this review article, current imaging techniques and clinical applications of MR imaging as a problem-solving tool for assessing mediastinal masses in pediatric patients are discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pediatric renal tumors may be malignant or benign. Wilms tumor, the most common malignant pediatric renal tumor, arises sporadically or with various syndromes. Renal cell carcinoma typically presents in older children. Renal clear cell sarcoma and rhabdoid tumor are typically less common, more aggressive, and present in younger children. Benign renal tumors include mesoblastic nephroma, multilocular cystic renal tumor, angiomyolipoma, and metanephric adenoma. Lymphoma and leukemia may secondarily involve the kidney. Although there is overlap in the imaging appearance of several pediatric renal tumors, magnetic resonance characteristics and clinical data narrow the differential diagnosis and suggest a specific diagnosis. This article reviews current MR techniques, as well as the common MR imaging characteristics of malignant and benign pediatric renal neoplasms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Administration of intravenous contrast media to children is a routine practice at many clinical imaging centers, that can involve special considerations. In this paper, we provide practical information to facilitate optimal performance and oversight of this task. We provide targeted screening questions that can help to identify high-risk pediatric patients for both iodine-based and gadolinium-based intravenous contrast media administration. These include children at risk for allergic-like reactions, thyroid dysfunction, contrast-induced nephropathy, and nephrogenic systemic fibrosis. We make recommendations for addressing "yes" responses to screening questions using risk stratification schema that are specific to children. We also present criteria for selecting children for premedication prior to intravenous contrast administration, and suggest pediatric regimens. Additionally, we discuss practical nuances of intravenous contrast media administration to children and provide a quick-reference table of appropriate treatments with pediatric dosages for adverse contrast reactions.

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 10 6 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures., (© 2018 UICC.)

Rationale: In 2013, the New York State Department of Health (NYSDOH) began a mandatory state-wide initiative to improve early recognition and treatment of severe sepsis and septic shock., Objectives: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted hospital mortality among adult patients with severe sepsis and septic shock., Methods: Cohort analysis included all patients from all 185 hospitals in New York State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of 113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183 hospitals met study inclusion criteria. NYSDOH required all hospitals to submit and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis bundles: lactate measurement, early blood cultures and antibiotic administration, fluids, and vasopressors) for early identification and treatment of severe sepsis or septic shock., Measurements and Main Results: Compliance with elements of the sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (P < 0.001), whereas among those eligible for the 6-hour bundle (n = 35,307) compliance increased from 23.9% to 30.8% (P < 0.001). Risk-adjusted mortality decreased from 28.8% to 24.4% (P < 0.001) in patients among whom a sepsis protocol was initiated. Greater hospital compliance with 3-hour and 6-hour bundles was associated with shorter length of stay and lower risk and reliability-adjusted mortality., Conclusions: New York's statewide initiative increased compliance with sepsis-performance measures. Risk-adjusted sepsis mortality decreased during the initiative and was associated with increased hospital-level compliance.

Background: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples., Methods: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses., Results: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades., Conclusions: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research., (© 2018 John Wiley & Sons Ltd.)

Importance: The death of a pediatric patient with sepsis motivated New York to mandate statewide sepsis treatment in 2013. The mandate included a 1-hour bundle of blood cultures, broad-spectrum antibiotics, and a 20-mL/kg intravenous fluid bolus. Whether completing the bundle elements within 1 hour improves outcomes is unclear., Objective: To determine the risk-adjusted association between completing the 1-hour pediatric sepsis bundle and individual bundle elements with in-hospital mortality., Design, Settings, and Participants: Statewide cohort study conducted from April 1, 2014, to December 31, 2016, in emergency departments, inpatient units, and intensive care units across New York State. A total of 1179 patients aged 18 years and younger with sepsis and septic shock reported to the New York State Department of Health who had a sepsis protocol initiated were included., Exposures: Completion of a 1-hour sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour., Main Outcomes and Measures: Risk-adjusted in-hospital mortality., Results: Of 1179 patients with sepsis reported at 54 hospitals (mean [SD] age, 7.2 [6.2] years; male, 54.2%; previously healthy, 44.5%; diagnosed as having shock, 68.8%), 139 (11.8%) died. The entire sepsis bundle was completed in 1 hour in 294 patients (24.9%). Antibiotics were administered to 798 patients (67.7%), blood cultures were obtained in 740 patients (62.8%), and the fluid bolus was completed in 548 patients (46.5%) within 1 hour. Completion of the entire bundle within 1 hour was associated with lower risk-adjusted odds of in-hospital mortality (odds ratio [OR], 0.59 [95% CI, 0.38 to 0.93], P = .02; predicted risk difference [RD], 4.0% [95% CI, 0.9% to 7.0%]). However, completion of each individual bundle element within 1 hour was not significantly associated with lower risk-adjusted mortality (blood culture: OR, 0.73 [95% CI, 0.51 to 1.06], P = .10; RD, 2.6% [95% CI, -0.5% to 5.7%]; antibiotics: OR, 0.78 [95% CI, 0.55 to 1.12], P = .18; RD, 2.1% [95% CI, -1.1% to 5.2%], and fluid bolus: OR, 0.88 [95% CI, 0.56 to 1.37], P = .56; RD, 1.1% [95% CI, -2.6% to 4.8%])., Conclusions and Relevance: In New York State following a mandate for sepsis care, completion of a sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour was associated with lower risk-adjusted in-hospital mortality among patients with pediatric sepsis and septic shock.