Exploratory factor analysis yields grouping of brain injury biomarkers significantly associated with outcomes in neonatal and pediatric ECMO.

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100ß, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRß, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

Real-world implications of IMACS malignancy screening guidelines for idiopathic inflammatory myopathies: An evaluation of compliance and economic impact at a tertiary referral center.

AIM: An inaugural set of consensus guidelines for malignancy screening in idiopathic inflammatory myopathy (IIM) were recently published by an international working group. These guidelines propose different investigation strategies based on "high", "intermediate" or "standard" malignancy risk groups. This study compares current malignancy screening practices at an Australian tertiary referral center with the recommendations outlined in these guidelines. METHODS: We conducted a retrospective analysis of newly diagnosed IIM patients. Relevant demographic and clinical data regarding malignancy screening were recorded. Existing practice was compared with the guidelines using descriptive statistics; costs were calculated using the Australian Medicare Benefit Schedule. RESULTS: Of the 47 patients identified (66% female, median age: 63 years [IQR: 55.5-70], median disease duration: 4 years [IQR: 3-6]), only one had a screening-detected malignancy. Twenty patients (43%) were at high risk, while 20 (43%) were at intermediate risk; the remaining seven (15%) had IBM, for which the proposed guidelines do not recommend screening. Only three (6%) patients underwent screening fully compatible with International Myositis Assessment and Clinical Studies recommendations. The majority (N = 39, 83%) were under-screened; the remaining five (11%) overscreened patients had IBM. The main reason for guideline non-compliance was the lack of repeated annual screening in the 3 years post-diagnosis for high-risk individuals (0% compliance). The mean cost of screening was substantially lower than those projected by following the guidelines ($481.52 [SD 423.53] vs $1341 [SD 935.67] per patient), with the highest disparity observed in high-risk female patients ($2314.29/patient). CONCLUSION: Implementation of the proposed guidelines will significantly impact clinical practice and result in a potentially substantial additional economic burden.

Diagnosing and characterizing inflammatory myopathies at an Australian tertiary public hospital: Resource utilization and direct healthcare costs.

AIM: To determine the direct health service costs and resource utilization associated with diagnosing and characterizing idiopathic inflammatory myopathies (IIMs), and to assess for limitations and diagnostic delay in current practice. METHODS: A retrospective, single-center cohort analysis of all patients diagnosed with IIMs between January 2012 and December 2021 in a large tertiary public hospital was conducted. Demographics, resource utilization and costs associated with diagnosing IIM and characterizing disease manifestations were identified using the hospital's electronic medical record and Health Intelligence Unit, and the Medicare Benefits Schedule. RESULTS: Thirty-eight IIM patients were identified. IIM subtypes included dermatomyositis (34.2%), inclusion body myositis (18.4%), immune-mediated necrotizing myopathy (18.4%), polymyositis (15.8%), and anti-synthetase syndrome (13.2%). The median time from symptom onset to diagnosis was 212 days (IQR: 118-722), while the median time from hospital presentation to diagnosis was 30 days (8-120). Seventy-six percent of patients required emergent hospitalization during their diagnosis, with a median length of stay of 8 days (4-15). The average total cost of diagnosing IIM was $15 618 AUD (STD: 11331) per patient. Fifty percent of patients underwent both MRI and EMG to identify affected muscles, 10% underwent both pan-CT and PET-CT for malignancy detection, and 5% underwent both open surgical and percutaneous muscle biopsies. Autoimmune serology was unnecessarily repeated in 37% of patients. CONCLUSION: The diagnosis of IIMs requires substantial and costly resource use; however, our study has identified potential limitations in current practice and highlighted the need for streamlined diagnostic algorithms to improve patient outcomes and reduce healthcare-related economic burden.

Normalised repeat serum prostate-specific antigen: associations with age and magnetic resonance imaging results.

OBJECTIVE: To assess the value of a repeat prostate-specific antigen measurement (PSA2) before magnetic resonance imaging (MRI) in men with a raised PSA (PSA1) <10 µg/L. METHOD: Medical records of men aged < 75 years referred in 2021 for PSA1 3.0-9.9 µg/L (< 70 years) or 5.0-9.9 µg/L (70-74 years) were reviewed. PSA2 was sampled before MRI within 60 days from PSA1. Odds ratios (ORs) were calculated with logistic regression. Chi-square and trend-test were used for categorical variables. RESULTS: A total of 341 men were included. Median time between PSA1 and PSA2 was 28 days (interquartile range 20-35 days). PSA normalised in 16% (95% confidence interval [CI]: 13-21). Younger men were more likely to have a normal PSA2 (OR: 0.95 per year older, 95% CI: 0.92-0.99). Among men aged < 70 years, those with PSA1 < 5 µg/L were more likely to have normalised PSA2 than those with PSA1 ≥ 5 µg/L (21% vs. 10%, p = 0.01). A greater proportion of men with normalised PSA2 had a Prostate Imaging Data and Reporting System MRI score of 1-3 than men with non-normalised PSA2 (93% vs. 77%, p = 0.01). CONCLUSIONS: A clinically significant proportion of men with a moderately raised PSA value have a normal PSA2. Younger men and men with lower PSA1 were more likely to have a normal PSA2. Few men with normalised PSA2 had suspicious MRI findings. Routine repeat PSA-testing may be motivated in men with a moderately raised PSA value to save MRI resources, particularly in younger men.

Request Dispatching Over Distributed SDN Control Plane: A Multiagent Approach.

Software-defined networking (SDN) allows flexible and centralized control in cloud data centers. An elastic set of distributed SDN controllers is often required to provide sufficient yet cost-effective processing capacity. However, this introduces a new challenge: Request Dispatching among the controllers by SDN switches. It is essential to design a dispatching policy for each switch to guide the request distribution. Existing policies are designed under certain assumptions, including a single centralized agent, global network knowledge, and a fixed number of controllers, which often cannot be satisfied in practice. This article proposes MADRina, Multiagent Deep Reinforcement Learning for request dispatching, to design policies with high dispatching adaptability and performance. First, we design a multiagent system to address the limitation of using a centralized agent with global network knowledge. Second, we propose a Deep Neural Network-based adaptive policy to enable request dispatching over an elastic set of controllers. Third, we develop a new algorithm to train the adaptive policies in a multiagent context. We prototype MADRina and build a simulation tool to evaluate its performance using real-world network data and topology. The results show that MADRina can significantly reduce response time by up to 30% compared to existing approaches.

Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

BACKGROUND: Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. METHODS: We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20 ml/min/1.73 m2 after 1 year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1 year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. RESULTS: Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. CONCLUSION: PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.

Hearing Loss and Sociodemographic Barriers to Health Care Access Using the All of Us Research Program.

OBJECTIVE: To explore how gender and low-income status independently influence general health care access in patients with hearing loss. STUDY DESIGN: Cross-sectional study. SETTING: National database. METHODS: Patients with a diagnosis of sensorineural hearing loss from the National Institutes of Health All of Us database were included. Data entered from May 2018 to November 2022 was analyzed. Patient demographics such as age, gender, educational level, and insurance status were assessed. Multivariate logistic regressions were performed for statistical evaluation. RESULTS: A subset of 8875 patients (48.3% male, mean age 69) were evaluated. After multivariate analysis, female participants were more likely than male participants to report difficulty affording prescribed medications (odds ratio [OR]: 1.7, p < .0005) and specialists (OR: 1.4, p < 0.005). Female patients were also more likely to delay care due to elder care responsibilities (OR: 2.6, p < .0005), employment obligations (OR: 1.7, p < .0005), and feelings of apprehension in seeing a provider (OR: 1.7, p < .0005). Finally, female participants reported feeling less likely to be involved in their own medical care compared to males (OR: 1.2, p < .005). Low-income (<$25,000) participants reported less likely to feel respected (OR: 3.2, p < .0005) and delivered understandable health information (OR: 2.3, p < .0005) by providers compared to participants of higher income. CONCLUSION: This work suggests that patients with hearing loss, female gender, and lower socioeconomic status independently introduce barriers to health care access and utilization. These factors should be considered in efforts to promote equity in the care of patients with hearing loss.

Assessing the Impact of a Note-Writing Session and Standardized Note Template on Medical Student Note Length and Quality.

PURPOSE: To determine whether a formal note-writing session and note template for medical students (MS) during the Core Clerkship in Pediatrics (CCP) increase note quality, shortens note length, and decreases time of documentation. METHODS: In this single site, prospective study, MS participating in an 8-week CCP received a didactic session on note-writing in the electronic health record (EHR) and utilized EHR template developed for the study. We assessed note quality (measured by Physician Documentation Quality Instrument-9 [PDQI-9]), note length and note documentation time in this group compared to MS notes on the CCP in the prior academic year. We used descriptive statistics and Kruskal-Wallis tests for analysis. RESULTS: We analyzed 121 notes written by 40 students in the control group and 92 notes writing by 41 students in the intervention group. Notes from the intervention group were more "up to date," "accurate," "organized," and "comprehensible" compared to the control group (P = 0.02, P = 0.04, P = 0.01, and P = 0.02, respectively). Intervention group notes received higher cumulative PDQI-9 scores compared to the control group (median score 38 (IQR 34-42) versus 36 (IQR 32-40) out of 45 total, P = 0.04). Intervention group notes were approximately 35% shorter than the control group notes (median 68.5 lines vs 105 lines, P < 0.0001) and were signed earlier than control group notes (median file time 316 minute vs 352 minute, P = 0.02). CONCLUSIONS: The intervention successfully decreased note length, improved note quality based on standardized metrics, and reduced time to completion of note documentation.

Endolymphatic Sac Surgery: Understanding the Historical Influence of Circumstance and Statistics.

In 1981, Danish physician Jens Thomsen conducted the first and only documented sham-controlled surgical trial in the history of otolaryngology. This trial is historically significant as it was the first in the field to use a methodologically sound study design to address a frustratingly complex disorder such as Ménière's disease. Despite this, historical interpretations of this work have varied, and questions about the results have been raised. We review the fascinating historical context of this landmark trial and detail how it was influenced by the rise of the randomized controlled trial. We examine how subsequent statistical analyses and interpretations of this historical work have affected surgical treatment paradigms in Ménière's disease, and we look forward to suggest the legacy of this work as a sham-controlled surgical trial in otolaryngology.

A National Analysis of Inpatient Pediatric Adenoidectomy.

OBJECTIVE: Hospital admission following pediatric adenoidectomy without tonsillectomy is not well characterized. The objective of our study is to better characterize risk factors for post-operative complications in younger children undergoing inpatient adenoidectomy. METHODS: A cross-sectional analysis using data derived from the Kid's Inpatient Database (KID) was performed. Study participants included children <3 years of age who underwent an adenoidectomy and were admitted to hospitals participating in the KID for years 1997, 2000, 2003, 2006, 2009, and 2012. Descriptive statistical analysis and a multivariate logistic regression analysis were performed to identify risk factors for post-operative complication. RESULTS: A total of 3406 children (mean age 1.1 ± 0.7 years) were included. The overall post-operative bleeding and respiratory complication rates were 0.6% and 5.4%, respectively. Children less than 18 months of age demonstrated increased rates of post-operative respiratory complications (P = .009), but not bleeding complications (P = .857). Presence of cardiopulmonary congenital malformations (OR 1.54, 95% CI 1.07-2.20), chronic respiratory disease of the newborn (OR 5.03, 95% CI 2.86-8.85), and neuromuscular disorders (OR 1.97, 95% CI 1.09-3.57) were associated with post-operative respiratory distress. CONCLUSIONS: This analysis of a national dataset suggests that otherwise healthy children less than 18 months of age and children 18 months to 3 years of age with certain comorbidities may benefit from overnight observation following adenoidectomy.

Telehealth in the times of SARS-CoV-2 infection for the otolaryngologist.

OBJECTIVE: In response to the American Academy of Otolaryngology - Head and Neck Surgery's recommendations to limit patient care activities in the times of SARS-CoV-2, many elective surgeries have been canceled without patient clinics transitioning to virtual visits. With regulations for telemedicine loosened, new possibilities for the practice of otolaryngology have opened. To address the uncertain duration of this pandemic, a review was conducted of current literature on use of telemedicine services in the current SARS-CoV-2 pandemic and in previous national emergencies to reveal the role telemedicine can play for otolaryngology practices. DATA SOURCES: Pubmed articles with an independent search query were utilized. METHODS: Literature review performed by one author searched for all published English-language literature on telehealth in the SARS-CoV-2 era. Articles were considered for discussion if they provided relevant developments for telemedicine in the context of the SARS-CoV-2 pandemic. RESULTS: Telemedicine can be up-scaled in the current SARS-CoV-2 pandemic where exposure containment is of the utmost priority. With patient interaction possible through virtual communication, telemedicine allows continued patient care while minimizing the risk of viral spread. In the realm of otolaryngology, telemedicine has been used in the past during disasters with other studies demonstrating high diagnostic concordance with inpatient visits. Many institutions have recognized the potential for such care as they begin utilize both virtual visits and in-person care during this pandemic. CONCLUSION: To limit the spread of SARS-CoV-2, we support the AAO-HNS recommendation for the adoption of novel ways to employ telemedicine in this era. Many emergency departments and health care systems have the infrastructure necessary for synchronous video telemedicine visits that can be leveraged to provide quality care with patients. With the continued need to socially distance, telemedicine can protect both physicians and patients from unnecessary exposure to the virus.

Head and neck survivorship care in the times of the SARS-CoV-2 pandemic.

With the arrival of the coronavirus disease (SARS-CoV-2) in the United States, care practice paradigms have drastically changed. Data from China suggest that the new virus poses additional risks as case fatality of patients with cancer was higher at 5.6% compared to 2.3% of the general population. There are three proposed major strategies to address care for patients with cancer in this SARS-CoV-2 pandemic with postponing treatment for those with stable cancer, increasing personal protection provisions for patients with cancer, and increasing monitoring if a patient becomes infected with SARS-CoV-2. In this present commentary, we discuss the unique mental health challenges and burdens of patients with head and neck cancer in the times of the SARS-CoV-2 pandemic and approaches to mitigate these stressors through telemedicine to reduce future burdens to the patient and the health care system.

Comparison of Materials Used for 3D-Printing Temporal Bone Models to Simulate Surgical Dissection.

OBJECTIVE: To identify 3D-printed temporal bone (TB) models that most accurately recreate cortical mastoidectomy for use as a training tool by comparison of different materials and fabrication methods. BACKGROUND: There are several different printers and materials available to create 3D-printed TB models for surgical planning and trainee education. Current reports using Acrylonitrile Butadiene Styrene (ABS) plastic generated via fused deposition modeling (FDM) have validated the capacity for 3D-printed models to serve as accurate surgical simulators. Here, a head-to-head comparison of models produced using different materials and fabrication processes was performed to identify superior models for application in skull base surgical training. METHODS: High-resolution CT scans of normal TBs were used to create stereolithography files with image conversion for application in 3D-printing. The 3D-printed models were constructed using five different materials and four printers, including ABS printed on a MakerBot 2x printer, photopolymerizable polymer (Photo) using the Objet 350 Connex3 Printer, polycarbonate (PC) using the FDM-Fortus 400 mc printer, and two types of photocrosslinkable acrylic resin, white and blue (FLW and FLB, respectively), using the Formlabs Form 2 stereolithography printer. Printed TBs were drilled to assess the haptic experience and recreation of TB anatomy with comparison to the current paradigm of ABS. RESULTS: Surgical drilling demonstrated that FLW models created by FDM as well as PC and Photo models generated using photopolymerization more closely recreated cortical mastoidectomy compared to ABS models. ABS generated odor and did not represent the anatomy accurately. Blue resin performed poorly in simulation, likely due to its dark color and translucent appearance. CONCLUSIONS: PC, Photo, and FLW models best replicated surgical drilling and anatomy as compared to ABS and FLB models. These prototypes are reliable simulators for surgical training.

Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH.

Studies in vivo have suggested the involvement of CREB-regulated transcription coactivator (CRTC)2 on ACTH-induced transcription of the key steroidogenic protein, Steroidogenic Acute Regulatory (StAR). The present study uses two ACTH-responsive adrenocortical cell lines, to examine the role of CRTC on Star transcription. Here we show that ACTH-induced Star primary transcript, or heteronuclear RNA (hnRNA), parallels rapid increases in nuclear levels of the 3 isoforms of CRTC; CRTC1, CRTC2 and CRTC3. Furthermore, ACTH promotes recruitment of CRTC2 and CRTC3 by the Star promoter and siRNA knockdown of either CRTC3 or CRTC2 attenuates the increases in ACTH-induced Star hnRNA. Using pharmacological inhibitors of PKA, MAP kinase and calcineurin, we show that the effects of ACTH on Star transcription and CRTC nuclear translocation depend predominantly on the PKA pathway. The data provides evidence that CRTC2 and CRTC3, contribute to activation of Star transcription by ACTH, and that PKA/CRTC-dependent pathways are part of the multifactorial mechanisms regulating Star transcription.

The SETD6 Methyltransferase Plays an Essential Role in Hippocampus-Dependent Memory Formation.

BACKGROUND: Epigenetic mechanisms are critical for hippocampus-dependent memory formation. Building on previous studies that implicate the N-lysine methyltransferase SETD6 in the activation of nuclear factor-κB RELA (also known as transcription factor p65) as an epigenetic recruiter, we hypothesized that SETD6 is a key player in the epigenetic control of long-term memory. METHODS: Using a series of molecular, biochemical, imaging, electrophysiological, and behavioral experiments, we interrogated the effects of short interfering RNA-mediated knockdown of Setd6 in the rat dorsal hippocampus during memory consolidation. RESULTS: Our findings demonstrate that SETD6 is necessary for memory-related nuclear factor-κB RELA methylation at lysine 310 and associated increases in H3K9me2 (histone H3 lysine 9 dimethylation) in the dorsal hippocampus and that SETD6 knockdown interferes with memory consolidation, alters gene expression patterns, and disrupts spine morphology. CONCLUSIONS: Together, these findings suggest that SETD6 plays a critical role in memory formation and may act as an upstream initiator of H3K9me2 changes in the hippocampus during memory consolidation.

Transient neonatal hypothyroidism following a short course of maternal amiodarone therapy.

Background Amiodarone is an iodine-rich medication used to treat maternal and fetal arrhythmias, with known effects on thyroid hormone homeostasis. Case presentation We describe a case of transient neonatal hypothyroidism following a short prenatal course of maternal amiodarone therapy resulting in neonatal TSH elevations exceeding those reported in the available literature.

Telencephalon transcriptome analysis of chronically stressed adult zebrafish.

Chronic stress leads to disruptions in learning and memory processes. The effects of chronic stress experience on the adult zebrafish brain, particularly the memory associated telencephalon brain region, is unclear. The goal of this study was to identify gene expression changes in the adult zebrafish brain triggered by chronic unpredictable stress. Transcriptome analysis of the telencephalon revealed 155 differentially expressed genes. Of these genes, some are critical genes involved in learning and memory, such as cdk5 and chrna7, indicating effects of chronic unpredictable stress on zebrafish memory. Interestingly, several genes were annotated in the Orange domain, which is an amino acid sequence present in eukaryotic DNA-binding transcription repressors. Furthermore, we identified hsd11b2, a cortisol inactivating gene, as chronic stress-responsive in the whole zebrafish brain. Collectively, these findings suggest that memory associated gene expression changes in adult zebrafish telencephalon are affected by chronic stress experience.

Risk factors for readmission in patients discharged with outpatient parenteral antimicrobial therapy: a retrospective cohort study.

BACKGROUND: Outpatient parenteral antimicrobial therapy (OPAT) is a practical and effective way of delivering antimicrobial therapy, but may be associated with significant risk for hospital readmission. This study aimed to elucidate risk factors related to 30-day readmissions in patients who were discharged with OPAT at Mount Sinai Beth Israel (MSBI). METHODS: This IRB approved retrospective cohort study included patients who were at least 18 years or older, admitted to MSBI from August 2015 to March 2016, and discharged to receive OPAT. Patients with intravenous antibiotics prescribed for chronic suppression or planned readmission within 30 days were excluded. The main outcome was readmission to the hospital within 30 days from previous hospital discharge. Univariate and logistic regression analyses were performed to determine predictors of 30-day readmission. RESULTS: There were a total of 200 patients included in the analysis; the median age was 60 years, 65.5% were male, and the median Charlson score was 2. A total of 155 (78%) patients received a peripherally inserted central catheter (PICC); the remainder was discharged with a midline. The most common medications prescribed for OPAT included cephalosporins (41%), vancomycin (31%), carbapenems (23%), and penicillins (16%). A total of 42 patients (21%) were readmitted within 30 days after previous discharge. Discharge to a skilled nursing facility or subacute rehabilitation center was found to be an independent predictor of readmission on logistic regression analyses (p <  0.05). CONCLUSION: Readmissions are common in patients discharged with OPAT. Recognizing predictors of readmission may help determine strategies to optimize care.