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Rationale: Survivors of hospitalization for community-acquired pneumonia (CAP) are at increased risk of cardiovascular events, repeat infections, and death in the following months but the cause is unknown.Objectives: To investigate whether persistent inflammation, defined as elevating circulating inflammatory markers at hospital discharge, is associated with subsequent outcomes.Methods: Prospective cohort study at 28 sites.Measurements and Main Results: We used standard criteria to define CAP and the National Death Index to determine all-cause and cause-specific 1-year mortality. At hospital discharge, 1,799 subjects (77.5%) were alive and vital signs had returned to normal in 1,512 (87%) subjects. The geometric means (+/-SD) for circulating IL-6 and IL-10 concentrations were 6.9 (+/-1) pg/ml and 1.2 (+/-1.1) pg/ml. At 1 year, 307 (17.1%) subjects had died. Higher IL-6 and IL-10 concentrations at hospital discharge were associated with an increased risk of death, which gradually fell over time. Using Gray's survival model, the associations were independent of demographics, comorbidities, and severity of illness (for each log-unit increase, the range of adjusted hazard ratios [HRs] for IL-6 were 1.02-1.46, P < 0.0001, and for IL-10 were 1.17-1.44, P = 0.01). The ranges of HRs for each log-unit increase in IL-6 and IL-10 concentrations among subjects who did and did not develop severe sepsis were 0.95-1.27 and 1.07-1.55, respectively. High IL-6 concentrations were associated with death due to cardiovascular disease, cancer, infections, and renal failure (P = 0.008).Conclusions: Despite clinical recovery, many patients with CAP leave hospital with ongoing subclinical inflammation, which is associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the perceptibility and acceptability CIEDE2000 (K L :K C :K H ) thresholds for lightness, chroma and hue differences in dentistry., Method: A Python-based program was developed to conduct a psychophysical experiment based on visual assessments of computer-simulated images of human teeth. The experiment was performed on a calibrated display. A 40-observer panel: dentists and laypersons (male and female; n=10), evalu- ated three subsets of simulated human teeth: the lightness subset (%∆L 00 ≥ 98 %), the chroma subset (%∆C 00 ≥ 98 %) and the hue subset (%∆H 00 ≥ 98 %), using ∆E 00 ≥ 5 units. A Takagi-Sugeno-Kang Fuzzy Approximation model was used as fitting procedure, and 50:50 % lightness, chroma and hue CIEDE2000 (1:1:1) and CIEDE2000 (2:1:1) perceptibility (PT 00 ) and accept- ability (AT 00 ) thresholds were calculated. Data was statistically analyzed using t-test (p < 0.05)., Results: The 50:50 % PT 00 for K L =1 were ∆L 00 =1.04, ∆C 00 =1.58 and ∆E 00 =1.01; and for K L =2 were ∆L 00 =0.51, ∆C 00 =1.58 and ∆E 00 =0.71. The 50:50 % AT 00 for K L =1 were ∆L 00 =2.82, ∆C 00 =3.04 and ∆E 00 =2.66; and for K L =2 were ∆L 00 =1.40, ∆C 00 =3.04 and ∆E 00 =1.78. PT 00 and AT 00 ∆H 00 may be considered no computable. A significant difference was found between CIEDE2000(1:1:1) and CIEDE2000(2:1:1), between lightness and chroma metrics, and between observer groups. No differences for lightness and chroma PT 00 were found between male and female groups., Conclusions: It is important to use PT 00 and AT 00 for lightness, chroma and hue specific to evaluate perceptual sensitivity for color changes in the tooth color space. AT 00 for lightness and chroma are influenced by the observer's experience and gender. Males and laypersons show more tolerance for changes in chroma (∆C 00 ) and in lightness (∆L 00 )., Significance: Hue and chroma mismatch are more difficult to be accepted in dental color space., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background Clinical outcome prediction based on acute-phase ischemic stroke data is valuable for planning health care resources, designing clinical trials, and setting patient expectations. Existing methods require individualized features and often involve manually engineered, time-consuming postprocessing activities. Purpose To predict the 90-day modified Rankin Scale (mRS) score with a deep learning (DL) model fusing noncontrast-enhanced CT (NCCT) and clinical information from the acute phase of stroke. Materials and Methods This retrospective study included data from six patient datasets from four multicenter trials and two registries. The DL-based imaging and clinical model was trained by using NCCT data obtained 1-7 days after baseline imaging and clinical data (age; sex; baseline and 24-hour National Institutes of Health Stroke Scale scores; and history of hypertension, diabetes, and atrial fibrillation). This model was compared with models based on either NCCT or clinical information alone. Model-specific mRS score prediction accuracy, mRS score accuracy within 1 point of the actual mRS score, mean absolute error (MAE), and performance in identifying unfavorable outcomes (mRS score, >2) were evaluated. Results A total of 1335 patients (median age, 71 years; IQR, 60-80 years; 674 female patients) were included for model development and testing through sixfold cross validation, with distributions of 979, 133, and 223 patients across training, validation, and test sets in each of the six cross-validation folds, respectively. The fused model achieved an MAE of 0.94 (95% CI: 0.89, 0.98) for predicting the specific mRS score, outperforming the imaging-only (MAE, 1.10; 95% CI: 1.05, 1.16; P < .001) and the clinical information-only (MAE, 1.00; 95% CI: 0.94, 1.05; P = .04) models. The fused model achieved an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.89, 0.92) for predicting unfavorable outcomes, outperforming the clinical information-only model (AUC, 0.88; 95% CI: 0.87, 0.90; P < .001) and the imaging-only model (AUC, 0.85; 95% CI: 0.84, 0.87; P < .001). Conclusion A fused DL-based NCCT and clinical model outperformed an imaging-only model and a clinical-information-only model in predicting 90-day mRS scores. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Lee in this issue.

Purpose: To explore utilization and efficacy of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in different sub-specialties of otolaryngology., Methods: A systematic search was performed using Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Medline, Clinicaltrials.gov, Scopus, and Google Scholar up to March 2024. English language randomized controlled trials with original data evaluating the use of PRP and PRF in various surgical and non-surgical procedures related to otolaryngologic sub-specialties. Dataset was limited to randomized controlled trials (RCTs) to have the best quality of evidence and possible recommendation., Results: Our database search resulted in 591 manuscripts. Four hundred twenty-six studies were primarily excluded after reviewing the title and abstract. The remaining 165 articles were studied completely, and 51 articles met the inclusion criteria. All the studies were RCTs and dated from 2001 to 2024. They included 19 studies related to otology, 10 studies related to rhinology, 7 studies related to facial plastic surgery, 6 studies related to head and neck surgery, 3 studies related to general otolaryngology, 3 studies related to pediatrics, 2 studies related to laryngology, and 1 study related to sleep medicine., Conclusion: PRP and PRF are safe, easy to use, and potentially effective treatment options for multiple otolaryngology pathologies. As an autologous material, there is no risk of immune reaction, and thus has been selected as a viable treatment option by many otolaryngologists. Larger studies would be helpful to confirm efficacy and allow for optimized patient selection for this treatment option., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Nurses are vital partners in the development of pediatric neurocritical care (PNCC) programs. Nursing expertise is acknowledged to be an integral component of high-quality specialty patient care in the field, but little guidance exists regarding educational requirements to build that expertise. We sought to obtain expert consensus from nursing professionals and physicians on curricular priorities for specialized PNCC nursing education in pediatric centers across the United States., Methods: We used a modified Delphi study technique surveying a multidisciplinary expert panel of nursing professionals and physicians. Online surveys were distributed to 44 panelists over three rounds to achieve consensus on curricular topics deemed essential for PNCC nursing education. During each round, panelists were asked to rate topics as essential or not essential, as well as given opportunities to provide feedback and suggest changes. Feedback was shared anonymously to the panelist group throughout the process., Results: From 70 initial individual topics, the consensus process yielded 19 refined topics that were confirmed to be essential for a PNCC nursing curriculum by the expert panel. Discrepancies existed regarding how universally to recommend topics of advanced neuromonitoring, such as brain tissue oxygenation; specialized neurological assessments, such as the serial neurological assessment in pediatrics or National Institutes of Health Stroke Scale; and some disease-based populations. Panelists remarked that not all centers see specific diseases, and not all centers currently employ advanced neuromonitoring technologies and skills., Conclusions: We report 19 widely accepted curricular priorities that can serve as a standard educational base for PNCC nursing. Developing education for nurses in PNCC will complement PNCC programs with targeted nursing expertise that extends comprehensive specialty care to the bedside. Further work is necessary to effectively execute educational certification programs, implement nursing standards in the field, and evaluate the impact of nursing expertise on patient care and outcomes., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Study Objective: Most long coronavirus disease (long COVID) studies rely on traditional surveillance methods that miss underserved populations who use emergency departments (EDs) as their primary health care source. In medically underserved ED populations, we sought to determine (1) whether there are gaps in awareness and self-declared understanding about long COVID illness, and (2) the prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms., Methods: This study was a cross-sectional, convenience sample survey study of adult patients at 11 geographically representative US EDs from December 2022 to October 2023. Awareness and self-declared understanding about long COVID illness were measured. Prevalence, impact on school/work attendance, and receipt of care for long COVID symptoms were also assessed., Results: Of 1,618 eligible patients, 1455 (89.9%) agreed to participate, including 33.4% African Americans and 30.9% Latino/a. Of the patients, 17.1% lacked primary care. In total, 33.2% had persistent COVID-19 symptoms lasting >1 month, and 20.3% had symptoms >3 months. Moreover, 49.8% with long COVID symptoms missed work/school because of symptoms; 30.3% of all participants and 33.5% of participants who had long COVID symptoms had prior awareness and self-declared understanding of long COVID. Characteristics associated with poor understanding of long COVID were African American race (adjusted odds ratio [aOR] 3.68, 95% confidence interval [CI] 2.66 to 5.09) and Latino/a ethnicity (aOR 3.16, 95% CI 2.15 to 4.64). Participants lacking primary care were less likely to have received long COVID care (24.6% versus 51.2%; difference 26.6%; 95% CI 13.7% to 36.9%)., Conclusions: Despite high prevalence and impact on school/work attendance of long COVID symptoms, most of this ED population had limited awareness and self-declared understanding of long COVID, and many had not received care. EDs should consider the development of protocols for diagnosis, education, and treatment of long COVID illness., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Fluorofluorophores are a unique class of fluorophores that can be solubilized in perfluorocarbons (PFCs) and used to study biological systems. However, because of the low dielectric constant and high oxygen solubility in the fluorous phase, the brightness and photostability of the fluorofluorophores are significantly diminished. Here, we leveraged the tight ion pairing in the fluorous phase to improve the photophysical properties of a fluorous soluble pentamethine dye (FCy5) via counterion exchange. We found that larger, softer, fluorinated, aryl borate counterions promote the ideal polymethine state where charge delocalization across the polymethine chain increases the brightness (6-fold) and photostability (55-fold) of FCy5., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Purpose To compare diffusion-weighted imaging (DWI) with thermal dosimetry as a noncontrast method to predict ablation margins in individuals with prostate cancer treated with MRI-guided focused ultrasound (MRgFUS) ablation. Materials and Methods This secondary analysis of a prospective trial (ClinicalTrials.gov no. NCT01657942) included 17 participants (mean age, 64 years ± 6 [SD]; all male) who were treated for prostate cancer using MRgFUS in whom DWI was performed immediately after treatment. Ablation contours from computed thermal dosimetry and DWI as drawn by two blinded radiologists were compared against the reference standard of ablation assessment, posttreatment contrast-enhanced nonperfused volume (NPV) contours. The ability of each method to predict the ablation zone was analyzed quantitively using Dice similarity coefficients (DSCs) and mean Hausdorff distances (mHDs). Results DWI revealed a hyperintense rim at the margin of the ablation zone. While DWI accurately helped predict treatment margins, thermal dose contours underestimated the extent of the ablation zone compared with the T1-weighted NPV imaging reference standard. Quantitatively, contour assessment between methods showed that DWI-drawn contours matched postcontrast NPV contours (mean DSC = 0.84 ± 0.05 for DWI, mHD = 0.27 mm ± 0.13) better than the thermal dose contours did (mean DSC = 0.64 ± 0.12, mHD = 1.53 mm ± 1.20) ( P < .001). Conclusion This study demonstrates that DWI, which can visualize the ablation zone directly, is a promising noncontrast method that is robust to treatment-related bulk motion compared with thermal dosimetry and correlates better than thermal dosimetry with the reference standard T1-weighted NPV. Keywords: Interventional-Body, Ultrasound-High-Intensity Focused (HIFU), Genital/Reproductive, Prostate, Oncology, Imaging Sequences, MRI-guided Focused Ultrasound, MR Thermometry, Diffusionweighted Imaging, Prostate Cancer ClinicalTrials.gov Identifier no. NCT01657942 Supplemental material is available for this article. © RSNA, 2024.

Small bowel strictures remain a debilitating consequence of Crohn's disease and contribute to poor outcomes for patients. Recently, TGFβ has been identified as an important driver of intestinal fibrosis. We studied the localization of TGFβ isoforms in ileal strictures of patients with Crohn's disease using in situ hybridization to understand TGFβ's role in stricture formation. The mucosa of strictures was characterized by higher TGFβ1 while the stricture submucosa showed higher TGFβ3 compared to normal ileum from patients without Crohn's disease (p = 0.02 and p = 0.044, respectively). We correlated these findings with single-cell transcriptomics which demonstrated that TGFβ3 transcripts overall are very rare, which may partially explain why its role in intestinal fibrosis has remained unclear to date. There were no significant differences in fibroblast or B cell TGFβ1 and/or TGFβ3 expression in inflamed vs. noninflamed ileum. We discuss the implications of these findings for therapeutic development strategies to treat patients with fibrostenotic Crohn's disease., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC)., Methods: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay., Results: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety., Conclusion: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Zumsteg’s spouse does legal work for Johnson & Johnson, Merck, Allergan, and Boehringer Ingelheim through her law firm]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Artificial intelligence (AI) is transforming the medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent scarcity of data associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatric patients compared with adult patients could also contribute to this challenge, as market size is a driver of commercialization. This review provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. Although current developments are promising, impediments due to the diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer learning of adult-based AI models to pediatric cancers, multiinstitutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking the full potential of AI for clinical translation and improving outcomes for these young patients.

Background: Many youth saw a rise in body mass index and obesity during the COVID-19 pandemic associated with virtual schooling and a lack of physical exercise options due to lockdown orders. However, the impact of the worldwide COVID-19 pandemic on body mass index in HIV-infected youth on anti-viral therapy has not been studied., Objective: This study examined COVID-19's impact on body mass index in 157 behaviorally acquired and 39 perinatally acquired youth living with HIV., Methods: Retrospective chart analysis was conducted for body mass index records across pre-COVID, COVID, and post-COVID periods., Results: Age and acquired type showed significant associations with increased body mass index. Limitations included missing data and physiological body mass index changes., Conclusion: The perinatally acquired group's body mass index increased by 1.6 during and 2.3 post-pandemic compared to pre-pandemic levels. Longitudinal follow-up of body mass index changes is needed in this vulnerable population., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: A personalized approach to assessing medication knowledge may identify opportunities for education to support self-management of cystic fibrosis (CF). This project describes the development, scoring, and preliminary validity of the Personalized CF Medication Questionnaire (PCF-MQ), designed to assess knowledge of prescribed CF medication purpose, administration, and dose and frequency., Methods: Participants completed the PCF-MQ, the Knowledge of Disease Management (KDM-CF), and the Cystic Fibrosis-Medication Beliefs Questionnaire (CF-MBQ). Prescribed regimens were abstracted from medical records. Eligibility criteria were age 12 years and older, diagnosed with CF, and prescribed a CF medication. Statistical analyses were conducted using R software. Spearman rho was used to test correlations between measures., Results: Sixty people with CF (pwCF) were enrolled; three people reported a regimen that substantially deviated from the medical record and were excluded from the analyses. The mean (SD) age was 20.2 (7.3) years, 54 % were female, and 74 % had a FEV1pp ≥70 %. The mean (SD) PCF-MQ total score was 77.8 (12.3) and knowledge scores ranged from a low of 58.3 for levalbuterol to 100 for ivacaftor. The PCF-MQ total score correlated with the KDM total score and subscales (Spearman Rho= 0.32-0.59, p < 0.05) and was not correlated with the CF-MBQ subscales (p > 0.05))., Conclusions: The PCF-MQ was correlated with another measure of general CF knowledge, but not health beliefs; because of the small sample size, this should be considered preliminary evidence of its validity. Advantages over existing CF knowledge measures include its practicality for use to help assess pwCF's knowledge about their prescribed regimen., Competing Interests: Declaration of competing interest Presented as a poster presentation at the 2020 North American Cystic Fibrosis Conference with abstract published in Pediatric Pulmonology (Phan H, Daines CL, Woo T, Goodman, A, Sawicki GS, Riekert KA. Design And Validation of The CF Medication Questionnaire. Pediatr Pulmonol. 2020; 55(S2): 264.), (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) is a non-invasive imaging technique for hemodynamic measurements. Various perfusion parameters, such as cerebral blood volume (CBV) and cerebral blood flow (CBF), can be derived from DSC-MRP, hence this non-invasive imaging protocol is widely used clinically for the diagnosis and assessment of intracranial pathologies. Currently, most institutions use commercially available software to compute the perfusion parametric maps. However, these conventional methods often have limitations, such as being time-consuming and sensitive to user input, which can lead to inconsistent results; this highlights the need for a more robust and efficient approach like deep learning. Using the relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) perfusion maps generated by FDA-approved software, we trained a multistage deep learning model. The model, featuring a combination of a 1D convolutional neural network (CNN) and a 2D U-Net encoder-decoder network, processes each 4D MRP dataset by integrating temporal and spatial features of the brain for voxel-wise perfusion parameters prediction. An auxiliary model, with similar architecture, but trained with truncated datasets that had fewer time-points, was designed to explore the contribution of temporal features. Both qualitatively and quantitatively evaluated, deep learning-generated rCBV and rCBF maps showcased effective integration of temporal and spatial data, producing comprehensive predictions for the entire brain volume. Our deep learning model provides a robust and efficient approach for calculating perfusion parameters, demonstrating comparable performance to FDA-approved commercial software, and potentially mitigating the challenges inherent to traditional techniques., (© 2024. The Author(s).)

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Michael DiLorenzo reports a relationship with GE Healthcare that includes: funding grants. Mark Fogel reports a relationship with Rocket Pharmaceuticals Inc that includes: consulting or advisory. Mark Fogel reports a relationship with CMP Pharma that includes: funding grants. Andrew Powell reports a relationship with Siemens Medical Solutions USA Inc that includes: consulting or advisory. Shaine Morris reports a relationship with Aytu BioPharma Inc that includes: non-financial support. Kanwal Farooqi reports a relationship with Bristol-Myers Squibb Foundation that includes: funding grants. Jonathan Soslow reports a relationship with Pfizer Inc that includes: consulting or advisory. Jonathan Soslow reports a relationship with Sarepta Therapeutics Inc that includes: consulting or advisory. Jonathan Soslow reports a relationship with Immunoforge that includes: consulting or advisory. Heynric Grotenhuis serves as an associate editor for JCMR. Mark Fogel and Andrew Powell serve as members of the editorial board for JCMR. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: While most adult ERCPs are performed on an outpatient basis, pediatric ERCPs are typically performed on an inpatient basis, or with ERCP followed by at least one night inpatient admission. We have begun performing a substantial proportion of our pediatric ERCPs on an outpatient basis, using our clinical judgment to guide the decision process. In the present study, we compare patient characteristics, indications, and adverse events associated with outpatient vs. inpatient ERCP., Methods: Using our endoscopy database, we identified patients 18 years of age and under who underwent ERCP from 2019 to 2021. Demographics, hospitalization status, indications, findings, interventions, as well as available adverse event and clinical outcomes data were analyzed., Results: 147 ERCP procedures were performed during the study period by one of two interventional endoscopists. A subset of 51 (34.7%) patients underwent outpatient ERCP. Comparison of the two groups (outpatient vs. inpatient ERCP) was notable for no statistically significant difference in patient age, range of indications, or proportion of index vs. subsequent ERCP. Overall rates of ERCP-associated adverse events were low and there was no statistically significant difference between adverse events in patients who underwent outpatient vs. inpatient ERCP., Conclusion: We analyzed outpatient and inpatient pediatric ERCP patient demographics and ERCP characteristics to identify factors that guide decision to determine whether pediatric ERCPs are performed on an outpatient vs. inpatient basis. There was no significant difference in adverse events associated with outpatient vs. inpatient pediatric ERCPs, attesting to the safety of outpatient ERCP for this subset of patients in the studied context. This is an area worthy of future prospective and multi-center study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Post-operative fluid restriction after transsphenoidal surgery (TSS) for pituitary tumors may effectively prevent delayed hyponatremia, the most common cause of readmission. However, implementation of individualized fluid restriction interventions after discharge is often complex and poses challenges for provider and patient. The purpose of this study was to understand the factors necessary for successful implementation of fluid restriction and discharge care protocols following TSS., Methods: Semi-structured interviews with fifteen patients and four caregivers on fluid discharge protocols were conducted following TSS. Patients and caregivers who had surgery before and after the implementation of updated discharge protocols were interviewed. Data were analyzed inductively using a procedure informed by rapid and thematic analysis., Results: Most patients and caregivers perceived fluid restriction protocols as acceptable and feasible when indicated. Facilitators to the protocols included clear communication about the purpose of and strategies for fluid restriction, access to the care team, and involvement of patients' caregivers in care discussions. Barriers included patient confusion about differences in the care plan between teams, physical discomfort of fluid restriction, increased burden of tracking fluids during recovery, and lack of clarity surrounding desmopressin prescriptions., Conclusion: Outpatient fluid restriction protocols are a feasible intervention following pituitary surgery but requires frequent patient communication and education. This evaluation highlights the importance of patient engagement and feedback to effectively develop and implement complex clinical interventions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: The majority of Physician assistant (PA) educators are women, yet men proportionately publish more and advance further in academic rank. This study examined if research interest, promotion goals, and perceptions of institutional support differed between PA educators with different gender identities., Methods: This is a subset analysis of a previously published cross-sectional study. PA programs were stratified by region and Carnegie classification and were sampled by a stratified random sampling method. PA faculty from selected programs were invited to participate in an anonymous survey. Data were analyzed to account for the stratified sample design. Means and proportions with associated 95% confidence intervals are described., Results: There was a 51% response rate (N = 110). Sixty-three percent of respondents identified as female and 36% as male. Men had a mean of 5.67 (0.17, 11.16) career research articles and women had 1.56 (0.68, 2.44) articles. Fifteen percent (3.7%, 26.3%) of men were full professor compared to 4.3% (0, 9.1%) of women. When transitioning to a faculty role, 72.5% (58.4%, 86.6%) of men and 52.9% (41%, 64.7%) of women felt supported by their institution. Both genders valued promotion, but 80% (67.6%, 92.4%) of men reported having clear 5-year goals compared to 58.8% (46.6%, 71%) of women (P = .034)., Conclusion: There was no statistical difference in publications between men and women in this study. Women felt less supported when transitioning to a faculty role compared to men. Both men and women valued promotion equally, but men reported working towards that goal more intentionally. This study found few consistent differences in the attitudes and behaviors towards scholarship between men and women., (Copyright © 2023 PA Education Association.)

Purpose: To describe the characteristics, management, and outcomes of pediatric patients with sporadic vestibular schwannoma (sVS)., Methods: This was a case series at a tertiary care center. Patients were identified through a research repository and chart review. Interventions were microsurgery, stereotactic radiosurgery (SRS), and observation. Outcome measures were tumor control, facial nerve function, and hearing., Results: Eight patients over 2006-2022 fulfilled inclusion criteria (unilateral VS without genetic or clinical evidence of neurofibromatosis type 2 (NF2); age ≤ 21) with a mean age of 17 years (14-20). Average greatest tumor length in the internal auditory canal was 9.7 mm (4.0-16.1). Average greatest tumor dimension (4/8 tumors) in the cerebellopontine angle was 19.1 mm (11.3-26.8). Primary treatment was microsurgery in five (62.5%) patients, observation in two (25%), and SRS in one (12.5%). Four (80%) surgical patients had gross total resections, and one (20%) had regrowth post-near total resection and underwent SRS. One observed patient and the primary SRS patient have remained radiographically stable for 3.5 and 7 years, respectively. The other observed patient required surgery for tumor growth after 12 months of observation. Two surgical patients had poor facial nerve outcomes. All post-procedural patients developed anacusis. Mean follow-up was 3 years (0.5-7)., Conclusions: We describe one of the largest reported cohorts of pediatric sVS in the USA. Diligent exclusion of NF2 is critical. Given the high likelihood of eventually requiring intervention and known adverse effects of SRS, microsurgery remains the preferred treatment. However, observation can be considered in select situations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The increasing linguistic and cultural diversity in the United States underscores the necessity of enhancing healthcare professionals' cross-cultural communication skills. This study focuses on incorporating interpreter and limited-English proficiency (LEP) patient training into the medical and physician assistant student curriculum. This aims to improve equitable care provision, addressing the vulnerability of LEP patients to healthcare disparities, including errors and reduced access. Though training is recognized as crucial, opportunities in medical curricula remain limited., Methods: To bridge this gap, a novel initiative was introduced in a medical school, involving second-year students in clinical sessions with actual LEP patients and interpreters. These sessions featured interpreter input, patient interactions, and feedback from interpreters and clinical preceptors. A survey assessed the perspectives of students, preceptors, and interpreters., Results: Outcomes revealed positive reception of interpreter and LEP patient integration. Students gained confidence in working with interpreters and valued interpreter feedback. Preceptors recognized the sessions' value in preparing students for future clinical interactions., Conclusions: This study underscores the importance of involving experienced interpreters in training students for real-world interactions with LEP patients. Early interpreter training enhances students' communication skills and ability to serve linguistically diverse populations. Further exploration could expand languages and interpretation modes and assess long-term effects on students' clinical performance. By effectively training future healthcare professionals to navigate language barriers and cultural diversity, this research contributes to equitable patient care in diverse communities., (© 2024. The Author(s).)

The newly released Segment Anything Model (SAM) is a popular tool used in image processing due to its superior segmentation accuracy, variety of input prompts, training capabilities, and efficient model design. However, its current model is trained on a diverse dataset not tailored to medical images, particularly ultrasound images. Ultrasound images tend to have a lot of noise, making it difficult to segment out important structures. In this project, we developed ClickSAM , which fine-tunes the Segment Anything Model using click prompts for ultrasound images. ClickSAM has two stages of training: the first stage is trained on single-click prompts centered in the ground-truth contours, and the second stage focuses on improving the model performance through additional positive and negative click prompts. By comparing the first stage's predictions to the ground-truth masks, true positive, false positive, and false negative segments are calculated. Positive clicks are generated using the true positive and false negative segments, and negative clicks are generated using the false positive segments. The Centroidal Voronoi Tessellation algorithm is then employed to collect positive and negative click prompts in each segment that are used to enhance the model performance during the second stage of training. With click-train methods, ClickSAM exhibits superior performance compared to other existing models for ultrasound image segmentation.

Background: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD., Methods: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models., Results: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found., Limitations: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores., Conclusions: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD., (© 2024. The Author(s).)

Background: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available., Methods: Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo. We conducted comprehensive functional, multi-omics (RNA sequencing and metabolomics studies), and genetic dependency studies both in vivo and in vitro to dissect the molecular mechanism, ERR isoform dependency, and target specificity., Results: Both SLU-PP-332 and SLU-PP-915 significantly improved ejection fraction, ameliorated fibrosis, and increased survival associated with pressure overload-induced HF without affecting cardiac hypertrophy. A broad spectrum of metabolic genes was transcriptionally activated by ERR agonists, particularly genes involved in fatty acid metabolism and mitochondrial function. Metabolomics analysis showed substantial normalization of metabolic profiles in fatty acid/lipid and tricarboxylic acid/oxidative phosphorylation metabolites in the mouse heart with 6-week pressure overload. ERR agonists increase mitochondria oxidative capacity and fatty acid use in vitro and in vivo. Using both in vitro and in vivo genetic dependency experiments, we show that ERRγ is the main mediator of ERR agonism-induced transcriptional regulation and cardioprotection and definitively demonstrated target specificity. ERR agonism also led to downregulation of cell cycle and development pathways, which was partially mediated by E2F1 in cardiomyocytes., Conclusions: ERR agonists maintain oxidative metabolism, which confers cardiac protection against pressure overload-induced HF in vivo. Our results provide direct pharmacologic evidence supporting the further development of ERR agonists as novel HF therapeutics., Competing Interests: Disclosures Dr Zhang is a cofounder of and consultant for Pelagos Pharmaceuticals Inc. The other authors report no conflicts of interest.

Objective: To compare tumor therapy response assessments with whole-body diffusion-weighted imaging (WB-DWI) and 18F-fluorodeoxyglucose ([ 18 F]FDG) PET/MRI in pediatric patients with Hodgkin lymphoma and non-Hodgkin lymphoma., Materials and Methods: In a retrospective, non-randomized single-center study, we reviewed serial simultaneous WB-DWI and [ 18 F]FDG PET/MRI scans of 45 children and young adults (27 males; mean age, 13 years ± 5 [standard deviation]; age range, 1-21 years) with Hodgkin lymphoma (n = 20) and non-Hodgkin lymphoma (n = 25) between February 2018 and October 2022. We measured minimum tumor apparent diffusion coefficient (ADCmin) and maximum standardized uptake value (SUVmax) of up to six target lesions and assessed therapy response according to Lugano criteria and modified criteria for WB-DWI. We evaluated the agreement between WB-DWI- and [ 18 F]FDG PET/MRI-based response classifications with Gwet's agreement coefficient (AC)., Results: After induction chemotherapy, 95% (19 of 20) of patients with Hodgkin lymphoma and 72% (18 of 25) of patients with non-Hodgkin lymphoma showed concordant response in tumor metabolism and proton diffusion. We found a high agreement between treatment response assessments on WB-DWI and [ 18 F]FDG PET/MRI (Gwet's AC = 0.94; 95% confidence interval [CI]: 0.82, 1.00) in patients with Hodgkin lymphoma, and a lower agreement for patients with non-Hodgkin lymphoma (Gwet's AC = 0.66; 95% CI: 0.43, 0.90). After completion of therapy, there was an excellent agreement between WB-DWI and [ 18 F]FDG PET/MRI response assessments (Gwet's AC = 0.97; 95% CI: 0.91, 1)., Conclusion: Therapy response of Hodgkin lymphoma can be evaluated with either [ 18 F]FDG PET or WB-DWI, whereas patients with non-Hodgkin lymphoma may benefit from a combined approach., Clinical Relevance Statement: Hodgkin lymphoma and non-Hodgkin lymphoma exhibit different patterns of tumor response to induction chemotherapy on diffusion-weighted MRI and PET/MRI., Key Points: • Diffusion-weighted imaging has been proposed as an alternative imaging to assess tumor response without ionizing radiation. • After induction therapy, whole-body diffusion-weighted imaging and PET/MRI revealed a higher agreement in patients with Hodgkin lymphoma than in those with non-Hodgkin lymphoma. • At the end of therapy, whole-body diffusion-weighted imaging and PET/MRI revealed an excellent agreement for overall tumor therapy responses for all lymphoma types., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Quantitative bibliometric indicators are widely used and widely misused for research assessments. Some metrics have acquired major importance in shaping and rewarding the careers of millions of scientists. Given their perceived prestige, they may be widely gamed in the current "publish or perish" or "get cited or perish" environment. This review examines several gaming practices, including authorship-based, citation-based, editorial-based, and journal-based gaming as well as gaming with outright fabrication. Different patterns are discussed, including massive authorship of papers without meriting credit (gift authorship), team work with over-attribution of authorship to too many people (salami slicing of credit), massive self-citations, citation farms, H-index gaming, journalistic (editorial) nepotism, journal impact factor gaming, paper mills and spurious content papers, and spurious massive publications for studies with demanding designs. For all of those gaming practices, quantitative metrics and analyses may be able to help in their detection and in placing them into perspective. A portfolio of quantitative metrics may also include indicators of best research practices (e.g., data sharing, code sharing, protocol registration, and replications) and poor research practices (e.g., signs of image manipulation). Rigorous, reproducible, transparent quantitative metrics that also inform about gaming may strengthen the legacy and practices of quantitative appraisals of scientific work., (© 2023. The Author(s).)

Background: Acute kidney injury (AKI) occurs commonly in pediatric septic shock and increases morbidity and mortality. Early identification of high-risk patients can facilitate targeted intervention to improve outcomes. We previously modified the renal angina index (RAI), a validated AKI prediction tool, to improve specificity in this population (sRAI). Here, we prospectively assess sRAI performance in a separate cohort., Methods: A secondary analysis of a prospective, multicenter, observational study of children with septic shock admitted to the pediatric intensive care unit from 1/2019 to 12/2022. The primary outcome was severe AKI (≥ KDIGO Stage 2) on Day 3 (D3 severe AKI), and we compared predictive performance of the sRAI (calculated on Day 1) to the original RAI and serum creatinine elevation above baseline (D1 SCr > Baseline +). Original renal angina fulfillment (RAI +) was defined as RAI ≥ 8; sepsis renal angina fulfillment (sRAI +) was defined as RAI ≥ 20 or RAI 8 to < 20 with platelets < 150 × 10 3 /µL., Results: Among 363 patients, 79 (22%) developed D3 severe AKI. One hundred forty (39%) were sRAI + , 195 (54%) RAI + , and 253 (70%) D1 SCr > Baseline + . Compared to sRAI-, sRAI + had higher risk of D3 severe AKI (RR 8.9, 95%CI 5-16, p < 0.001), kidney replacement therapy (KRT) (RR 18, 95%CI 6.6-49, p < 0.001), and mortality (RR 2.5, 95%CI 1.2-5.5, p = 0.013). sRAI predicted D3 severe AKI with an AUROC of 0.86 (95%CI 0.82-0.90), with greater specificity (74%) than D1 SCr > Baseline (36%) and RAI + (58%). On multivariable regression, sRAI + retained associations with D3 severe AKI (aOR 4.5, 95%CI 2.0-10.2, p < 0.001) and need for KRT (aOR 5.6, 95%CI 1.5-21.5, p = 0.01)., Conclusions: Prediction of severe AKI in pediatric septic shock is important to improve outcomes, allocate resources, and inform enrollment in clinical trials examining potential disease-modifying therapies. The sRAI affords more accurate and specific prediction than context-free SCr elevation or the original RAI in this population., (© 2023. The Author(s).)

Competing Interests: Disclosures of Conflicts of Interest: A.S.C. Contracts/grants to institution from GE HealthCare, Philips, and NIH; royalties/licenses from LVIS; consulting fees from Subtle Medical and Patient Square Capital; participation on a data safety monitoring board or advisory board for Brain Key and Chondrometrics; stock/stock options in Brain Key, Subtle Medical, and LVIS. C.B. No relevant relationships. D.O. Grants/contracts to institution from NIH, Alexion, and AHA; consulting fees from AZ, InVision, and Pfizer; payment or honoraria from Japanese Society of Echo and Korean Society of Echo.

Imaging of the joint in response to loading stress may provide additional measures of joint structure and function beyond conventional, static imaging studies. Exercise such as running, stair climbing, and squatting allows evaluation of the joint response to larger loading forces than during weight bearing. Quantitative MRI (qMRI) may assess properties of cartilage and meniscus hydration and organization in vivo that have been investigated to assess the functional response of these tissues to physiological stress. [ 18 F]sodium fluoride ([ 18 F]NaF) interrogates areas of newly mineralizing bone and provides an opportunity to study bone physiology, including perfusion and mineralization rate, as a measure of joint loading stress. In this review article, methods utilizing quantitative MRI, PET, and hybrid PET-MRI systems for assessment of the joint response to loading from exercise in vivo are examined. Both methodology and results of various studies performed are outlined and discussed. Lastly, the technical considerations, challenges, and future opportunities for these approaches are addressed., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Diversity-generating and mobile genetic elements are key to microbial and viral evolution and can result in evolutionary leaps. State-of-the-art algorithms to detect these elements have limitations. Here, we introduce DIVE, a new reference-free approach to overcome these limitations using information contained in sequencing reads alone. We show that DIVE has improved detection power compared to existing reference-based methods using simulations and real data. We use DIVE to rediscover and characterize the activity of known and novel elements and generate new biological hypotheses about the mobilome. Building on DIVE, we develop a reference-free framework capable of de novo discovery of mobile genetic elements., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Importance: Chronic subjective tinnitus, the perception of sound without an external source for longer than six months, may be a greatly debilitating condition for some people, and is associated with psychiatric comorbidities and high healthcare costs. Current treatments are not beneficial for all patients and there is a large need for new therapies for tinnitus., Observations: Unlike rarer cases of objective tinnitus, chronic subjective tinnitus often has no obvious etiology and a diverse pathophysiology. In the absence of objective testing, diagnosis is heavily based on clinical assessment. Management strategies include hearing aids, sound masking, tinnitus retraining therapy, cognitive behavioral therapy, and emerging therapies including transcranial magnetic stimulation and electrical stimulation., Conclusions and Relevance: Although current treatments are limited, emerging diagnostics and treatments provide promising avenues for the management of tinnitus symptoms.

Activity-dependent myelination is a fundamental mode of brain plasticity which significantly influences network function. We recently discovered that absence seizures, which occur in multiple forms of generalized epilepsy, can induce activity-dependent myelination, which in turn promotes further progression of epilepsy. Structural alterations of myelin are likely to be widespread, given that absence seizures arise from an extensive thalamocortical network involving frontoparietal regions of the bilateral hemispheres. However, the temporal course and spatial extent of myelin plasticity is unknown, due to limitations of gold-standard histological methods such as electron microscopy (EM). In this study, we leveraged magnetization transfer and diffusion MRI for estimation of g-ratios across major white matter tracts in a mouse model of generalized epilepsy with progressive absence seizures. EM was performed on the same brains after MRI. After seizure progression, we found increased myelination (decreased g-ratios) throughout the anterior portion (genu-to-body) of the corpus callosum but not in the posterior portion (body-splenium) nor in the fornix or the internal capsule. Curves obtained from averaging g-ratio values at every longitudinal point of the corpus callosum were statistically different with p<0.001. Seizure-associated myelin differences found in the corpus callosum body with MRI were statistically significant (p = 0.0027) and were concordant with EM in the same region (p = 0.01). Notably, these differences were not detected by diffusion tensor imaging. This study reveals widespread myelin structural change that is specific to the absence seizure network. Furthermore, our findings demonstrate the potential utility and importance of MRI-based g-ratio estimation to non-invasively detect myelin plasticity., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Adherence to survivorship care is suboptimal among pediatric and adolescent/young adult (AYA) cancer survivors. We evaluated predictors of cancer center-based follow-up among pediatric/AYA cancer survivors, with an emphasis on social determinants of health (SDOH)., Methods: This retrospective cohort study used electronic health record data at an academic medical center to identify patients aged 0-29 years at last cancer treatment who completed treatment 2010-2019. Cancer center-based follow-up was defined by oncology or survivorship clinic visits through 12/31/2022. Multivariate logistic regression models (overall, ages 0-19 [pediatric], 20-29 [YA]) evaluated the association of demographics, clinical/treatment characteristics, and SDOH (insurance type, distance to cancer center, area deprivation index) with clinic attendance. Further modeling accounted for the service area of a community-based organization (CBO) that supports families of children with cancer., Results: A total of 2210 survivors were included (56% pediatric, 44% YA; 66% non-White). Cancer center-based follow-up decreased from 94% 1-year post-treatment to 35% at > 5-7 years. In adjusted analysis, AYAs had the lowest follow-up (5-7 years post-treatment: OR 0.25 [0.15-0.41] for age 25-29; OR 0.25 [0.16-0.41] for age 20-24; OR 0.32 [0.20-0.52] for age 15-19). Survivors residing within the CBO service area were twice as likely to follow-up (OR 2.10 [1.34-3.29])., Conclusions: Among a diverse population, AYA survivors were vulnerable to loss to follow-up. Other SDOH were not consistently associated with follow-up. Support from a CBO may partly explain these findings., Implications for Cancer Survivors: CBOs may strengthen survivorship follow-up within medically underserved communities. More research is needed to understand community support in survivorship., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Prenatal maternal psychological distress (PMPD) is a known risk factor for adverse birth outcomes. N6-methyladenosine RNA (m6A) methylation is crucial in moderating RNA biology. This study aimed to evaluate the relationships between PMPD, birth outcomes, and placental m6A methylation., Methods: This was a prospective cohort study. PMPD exposure was assessed by questionnaires about prenatal stress, depression, and anxiety. Placental m6A methylation was measured using a colorimetric assay. The relationships between PMPD, m6A methylation, gestational age (GA), and birth weight (BW) were analyzed using structural equation models (SEMs). Maternal weight gain during pregnancy and infant sex were included as covariables., Results: The study included 209 mother-infant dyads. In an adjusted SEM, PMPD was associated with BW (B = -26.034; 95 % CI: -47.123, -4.868) and GA (B = -0.603; 95 % CI: -1.102, -0.154). M6A methylation was associated with PMPD (B = 0.055; 95 % CI: 0.040,0.073) and BW (B = -305.799; 95 % CI: -520.164, -86.460) but not GA. The effect of PMPD on BW was partially mediated by m6A methylation (B = -16.817; 95 % CI: -31.348, -4.638) and GA (B = -12.280; 95 % CI: -23.612, -3.079). Maternal weight gain was associated with BW (B = 5.113; 95 % CI: 0.229,10.438)., Limitations: The study sample size was small, and the specific mechanism of m6A methylation on birth outcomes needs to be further explored., Conclusions: In this study, PMPD exposure negatively affected BW and GA. Placental m6A methylation was associated with PMPD and BW and partially mediated the effect of PMPD on BW. Our findings highlight the importance of perinatal psychological evaluation and intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The present study tests the hypothesis that changes in the glucose sensitivity of lateral hypothalamus (LH) hypocretin/orexin glucose-inhibited (GI) neurons following weight loss leads to glutamate plasticity on ventral tegmental area (VTA) dopamine neurons and drives food seeking behavior., Methods: C57BL/6J mice were calorie restricted to a 15% body weight loss and maintained at that body weight for 1 week. The glucose sensitivity of LH hypocretin/orexin GI and VTA dopamine neurons was measured using whole cell patch clamp recordings in brain slices. Food seeking behavior was assessed using conditioned place preference (CPP)., Results: 1-week maintenance of calorie restricted 15% body weight loss reduced glucose inhibition of hypocretin/orexin GI neurons resulting in increased neuronal activation with reduced glycemia. The effect of decreased glucose on hypocretin/orexin GI neuronal activation was blocked by pertussis toxin (inhibitor of G-protein coupled receptor subunit Gα i/o ) and Rp-cAMP (inhibitor of protein kinase A, PKA). This suggests that glucose sensitivity is mediated by the Gα i/o -adenylyl cyclase-cAMP-PKA signaling pathway. The excitatory effect of the hunger hormone, ghrelin, on hcrt/ox neurons was also blocked by Rp-cAMP suggesting that hormonal signals of metabolic status may converge on the glucose sensing pathway. Food restriction and weight loss increased glutamate synaptic strength (indexed by increased AMPA/NMDA receptor current ratio) on VTA dopamine neurons and the motivation to seek food (indexed by CPP). Chemogenetic inhibition of hypocretin/orexin neurons during caloric restriction and weight loss prevented these changes in glutamate plasticity and food seeking behavior., Conclusions: We hypothesize that this change in the glucose sensitivity of hypocretin/orexin GI neurons may drive, in part, food seeking behavior following caloric restriction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: As a congenital anomaly, ureteroceles occur in 1 in 4000 children, and are usually diagnosed prenatally. However, there remains a lack of definite consensus on the optimal management of congenital ureteroceles., Objective: We evaluated factors associated with success of primary transurethral incision (TUI) in ureterocele pediatric patients., Methods: Demographic and clinical information for 120 pediatric patients who were diagnosed with congenital ureterocele between 1993 and 2021 at our institution were obtained through retrospective chart review. Data were analyzed using Fisher's exact tests, t-tests, and logistic regression with a significance threshold of p < 0.05. The primary outcome of ureterocele management was TUI effectiveness, defined by no need for further surgical intervention., Results: Of the 120 patients (39 boys, 81 girls) with ureteroceles, 75 patients (22 boys, 53 girls) met our inclusion criteria of undergoing initial TUI ureterocele. Initial TUI was effective in 51/75 patients (68.0%). We analyzed possible correlative factors for TUI efficacy. Simplex system was a significant predictor of primary TUI efficacy (85% effective in simplex systems, 62% in duplex systems). Prior urinary tract infection, prenatal diagnosis, and electrocautery technique were all associated with an increased risk of needing additional surgeries after primary TUI., Discussion: The most significant predictors of effective primary TUI were simplex system and the absence of preoperative vesicoureteral reflux. Prenatal diagnosis, preoperative febrile urinary tract infection, higher preoperative hydronephrosis grade, and the use of electrocautery were all associated with decreased primary TUI efficacy. Study limitations include that it was a retrospective chart review, and cohort size was limited by incomplete urology follow-up and operative records., Conclusions: Initial TUI was an effective procedure for the majority of our pediatric ureterocele patients, a higher success rate compared to other cohorts. Patients with a simplex system were more likely to have an effective first TUI than patients with duplex systems, as were patients without preoperative reflux. Although not statistically significant, our data suggest prior UTI, prenatal diagnosis, higher preoperative hydronephrosis grade, and the use of electrocautery may be associated with having additional surgeries., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Comorbidities such as chronic lung disease and gastroesophageal reflux (GERD), prematurity, and numerous other conditions may impact the success of LTR. Single-center studies are limited in terms of patient numbers and may be underpowered., Objectives: To analyze the impact of specific comorbidities on the operation-specific and overall surgical success of LTR in a large multicenter cohort and validate a predictive model for surgical success., Methods: A large retrospective multicenter 10-year review was undertaken to validate the data of a previous single-center study (Wertz et al. Laryngoscope 2020) which identified specific predictive comorbidities which impacted LTR outcomes. A Monte Carlo simulation based on the previous data set suggested that 300-400 cases would be needed to optimize the statistical power of a Bayesian model developed from the single-center data to predict surgical success. An IRB-approved data-sharing agreement was executed for 4 large U.S., Centers: A virtual REDCap® data entry form inquired about patient characteristics that best predicted surgical success in the single-center model. These included demographics, surgical approaches, cardiac, airway, genetic, endocrine, musculoskeletal, gastrointestinal, and pulmonary comorbidities; details of the surgical procedures, and results of esophagogastroduodenoscopy (EGD), esophageal pH/impedance and flexible bronchoscopy with bronchioalveolar lavage (BAL) were included. Surgical success defined as successful decannulation or resolution of airway symptoms was recorded as single surgery success and overall success following open surgical revision surgery. Multivariate Bayesian analysis, logistical regression, and Kaplan-Meier analysis were performed., Results: 542 patients were identified, including 165 from the single-center study and an additional 377 patients from the multicenter group. The median age was 36 months at the time of the most recent surgery. 70.9% of the LTRs were double-staged procedures. The overall success rate was 86.4% and operation-specific success rate was 69.2%. The specific comorbidities and aerodigestive test results that impacted success based on univariate analysis included staging, bronchiectasis, pulmonary hypertension, GERD, ASD, PDA, grade of stenosis, advanced levels of stenosis, Trisomy 21, MRSA, prior open surgery at another hospital, and gross appearance on EGD. Bayesian model averaging with backward selection was used to validate and refine a predictive model for surgical success with favorable receiver operating curve characteristics - AUC values of 0.827 for single surgery success and 0.797 for overall success., Discussion: With over 500 patients reviewed, this was the largest multicenter study of LTR to date, which elucidated the impact of comorbidities on success with LTR and was able to improve upon the predictive modeling based on single-center data. Patient factors are most critical in the outcome of LTR. Stage and levels of stenosis, as well as pulmonary and GI conditions most strongly impact the likelihood of success. Future prospective case-control studies will be performed to further optimize the current model for outcome prediction and patient management., Competing Interests: Declaration of competing interest All The authors have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Studies in critically ill adults demonstrate associations between serum renin concentrations (a proposed surrogate for renin-angiotensin-aldosterone system dysregulation) and poor outcomes, but data in critically ill children are lacking. We assessed serum renin + prorenin concentrations in children with septic shock to determine their predictive ability for acute kidney injury (AKI) and mortality., Methods: We conducted a secondary analysis of a multicenter observational study of children aged 1 week to 18 years admitted to 14 pediatric intensive care units (PICUs) with septic shock and residual serum available for renin + prorenin measurement. Primary outcomes were development of severe persistent AKI (≥ KDIGO stage 2 for ≥ 48 h) in the first week and 28-day mortality., Results: Among 233 patients, day 1 median renin + prorenin concentration was 3436 pg/ml (IQR 1452-6567). Forty-two (18%) developed severe persistent AKI and 32 (14%) died. Day 1 serum renin + prorenin predicted severe persistent AKI with an AUROC of 0.75 (95% CI 0.66-0.84, p < 0.0001; optimal cutoff 6769 pg/ml) and mortality with an AUROC of 0.79 (95% CI 0.69-0.89, p < 0.0001; optimal cutoff 6521 pg/ml). Day 3/day 1 (D3:D1) renin + prorenin ratio had an AUROC of 0.73 (95% CI 0.63-0.84, p < 0.001) for mortality. On multivariable regression, day 1 renin + prorenin > optimal cutoff retained associations with severe persistent AKI (aOR 6.8, 95% CI 3.0-15.8, p < 0.001) and mortality (aOR 6.9, 95% CI 2.2-20.9, p < 0.001). Similarly, D3:D1 renin + prorenin > optimal cutoff was associated with mortality (aOR 7.6, 95% CI 2.5-23.4, p < 0.001)., Conclusions: Children with septic shock have very elevated serum renin + prorenin concentrations on PICU admission, and these concentrations, as well as their trend over the first 72 h, predict severe persistent AKI and mortality. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Objective: The effectiveness of lecture-based (LB) formats for residency education has recently been challenged as the gold standard. Studies suggest a flipped classroom (FC) lecture improves resident satisfaction, but evidence that showing improved knowledge acquisition is lacking. To determine whether the flipped classroom model improves knowledge acquisition compared to traditional LB model., Methods: Emergency medicine resident physicians at 2 academic programs were included in December 2019; at Sinai-Grace Hospital, a traditional lecture was the teaching method and at Detroit Receiving Hospital, FC was utilized. Residents completed prelecture and postlecture content tests. The primary outcome was change in test results (pretest to post-test). A noninferiority design comparing the changes between intervention and control groups was utilized (1-sided t-test, noninferiority margin of -0.5; 1-sided alpha = 0.05)., Results: Results were available for 31 residents (17 controls and 14 interventions) out of 83 enrolled. There were 14 postgraduate year 1 (PGY-1), 9 PGY-2, and 8 PGY-3 residents. The mean difference in score was +0.71 (SD 1.38) and +0.77 (SD 1.48) for the FC and LB groups, respectively. This resulted in a mean difference between groups of -0.05 (lower bound of the upper 95% confidence interval -0.93 and therefore crossing the noninferiority margin of -0.05; P  = .20)., Conclusions: This study of resident education at 2 training programs was unable to demonstrate noninferiority of an FC format compared to standard lecture. Surprisingly, there was little improvement in test results after both teaching formats. Larger studies are needed to power results., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

We propose an interpretable and scalable model to predict likely diagnoses at an encounter based on past diagnoses and lab results. This model is intended to aid physicians in their interaction with the electronic health records (EHR). To accomplish this, we retrospectively collected and de-identified EHR data of 2,701,522 patients at Stanford Healthcare over a time period from January 2008 to December 2016. A population-based sample of patients comprising 524,198 individuals (44% M, 56% F) with multiple encounters with at least one frequently occurring diagnosis codes were chosen. A calibrated model was developed to predict ICD-10 diagnosis codes at an encounter based on the past diagnoses and lab results, using a binary relevance based multi-label modeling strategy. Logistic regression and random forests were tested as the base classifier, and several time windows were tested for aggregating the past diagnoses and labs. This modeling approach was compared to a recurrent neural network based deep learning method. The best model used random forest as the base classifier and integrated demographic features, diagnosis codes, and lab results. The best model was calibrated and its performance was comparable or better than existing methods in terms of various metrics, including a median AUROC of 0.904 (IQR [0.838, 0.954]) over 583 diseases. When predicting the first occurrence of a disease label for a patient, the median AUROC with the best model was 0.796 (IQR [0.737, 0.868]). Our modeling approach performed comparably as the tested deep learning method, outperforming it in terms of AUROC (p < 0.001) but underperforming in terms of AUPRC (p < 0.001). Interpreting the model showed that the model uses meaningful features and highlights many interesting associations among diagnoses and lab results. We conclude that the multi-label model performs comparably with RNN based deep learning model while offering simplicity and potentially superior interpretability. While the model was trained and validated on data obtained from a single institution, its simplicity, interpretability and performance makes it a promising candidate for deployment., (© 2023. The Author(s).)