Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Quantitative pupillometry as a biomarker for prediction of return to play in mild traumatic brain injury: a Military Traumatic Brain Injury Initiative study.

OBJECTIVE: This study aimed to determine the validity of quantitative pupillometry to predict the length of time for return to full activity/duty after a mild traumatic brain injury (mTBI) in a cohort of injured cadets at West Point. METHODS: Each subject received baseline (T0) quantitative pupillometry, in addition to evaluation with the Balance Error Scoring System (BESS), Standardized Assessment of Concussion (SAC), and Sport Concussion Assessment Tool 5th Edition Symptom Survey (SCAT5). Repeat assessments using the same parameters were conducted within 48 hours of injury (T1), at the beginning of progressive return to activity (T2), and at the completion of progressive return to activity protocols (T3). Pupillary metrics were compared on the basis of length of time to return to full play/duty and the clinical scores. RESULTS: The authors' statistical analyses found correlations between pupillometry measures at T1, including end-initial diameter and maximum constriction velocity, with larger change and faster constriction predicting earlier return to play. There was also an association with maximum constriction velocity at baseline (T0), predicting faster return to play. CONCLUSIONS: The authors conclude that that pupillometry may be a valuable tool for assessing time to return to duty from mTBI by providing a measure of baseline resiliency to mTBI and/or autonomic dysfunction in the acute phase after mTBI.

Anal human papillomavirus (HPV) disagreement by Linear Array compared to SPF10 PCR-DEIA-LiPA25 system in young sexual minority men.

Introduction: Young sexual minority men (SMM) bear the greatest burden of anal human papillomavirus (HPV) infections. We assessed anal HPV genotype discordance between the Linear Array (LA) and SPF10 PCR-DEIA-LiPA25 (LiPA25). Methods: Discordance was assessed between LA and LiPA25 using self-collected anal swabs from 120 SMM aged 18-29 who were recruited in 2014-2016. Multiple-type infection was explored as a potential confounder of testing agreement, along with clinical and behavioral factors such as HIV status, syphilis status, incarceration history, health insurance coverage, having 3 or more sex partners in the past 6 months, and co-infection with HPV-16. Results: Significant discordance was found for HPV-6, -11, -16, -31, -42, -54, and -59. Exploratory analyses suggest higher prevalence of genotype discordance in those living with HIV, those with 3 or more sex partners, and those who were positive for 4 or more HPV types. Conclusions: Our results highlight the importance of HPV detection methods which may inform different interpretations of research assessing anal HPV natural history among SMM at highest risk for HPV.

Discovery of the Lipopeptides Albubactins A-H from Streptomyces albidoflavus RKJM0023 via Chemical Elicitation with Rhamnolipids and Synthesis of Albubactin A.

The marine tunicate-derived Streptomyces albidoflavus RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based molecular networking analysis enhanced with nonparametric statistics highlighted the upregulation of a molecular cluster (Kruskal-Wallis p = 1.6 e-6 for 1) in which no MS/MS features had library matches. Targeted isolation of these features resulted in the discovery of nine new N-acylated lipopeptides, albubactins A-H (1-8) each containing a unique glutamine tripeptide and a C-terminal ethyl ester moiety. Three related albubactin acids A-C (9-11) lacking the ethyl ester were also identified. NMR spectroscopy and UPLC-HR-ESI-MS/MS demonstrated that the albubactins were obtained as mixtures that shared a common m/z and differed only in their acylated terminal groups. Due to the complex spectroscopic elucidation with many overlapping shifts, a total synthesis of albubactin A (1) was completed and used to determine the absolute configuration of the new albubactins.

Consistency of metabolite associations with measured glomerular filtration rate in children and adults.

Background: There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation. Methods: We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < -0.5), we assessed additional variation by age (height in children), sex, race and body mass index (BMI). Results: A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates and nucleotides were more often negatively correlated with mGFR compared with lipids, but there was no association with metabolite molecular weight, liquid chromatography/mass spectrometry platform and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r < -0.5), 27 were consistently not associated with age (height in children), sex or race. Conclusions: The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR.

Quasi-bound states in the continuum for electromagnetic induced transparency and strong excitonic coupling.

Advancing on previous reports, we utilize quasi-bound states in the continuum (q-BICs) supported by a metasurface of TiO2 meta-atoms with broken inversion symmetry on an SiO2 substrate, for two possible applications. Firstly, we demonstrate that by tuning the metasurface's asymmetric parameter, a spectral overlap between a broad q-BIC and a narrow magnetic dipole resonance is achieved, yielding an electromagnetic induced transparency analogue with a 50 µs group delay. Secondly, we have found that, due to the strong coupling between the q-BIC and WS2 exciton at room temperature and normal incidence, by integrating a single layer of WS2 to the metasurface, a 37.9 meV Rabi splitting in the absorptance spectrum with 50% absorption efficiency is obtained. These findings promise feasible two-port devices for visible range slow-light characteristics or nanoscale excitonic coupling.

Impact of Embolisate Penetration, Type, and Technique on Results After Standalone Middle Meningeal Artery Embolization for Chronic Subdural Hematoma.

BACKGROUND AND OBJECTIVES: Middle meningeal artery embolization (MMAE) has emerged as a promising modality for chronic/subacute subdural hematoma treatment; however, consensus regarding embolization technique and embolisate has not been achieved. We thus sought to compare the efficacy of distinct MMAE techniques and embolisate. METHODS: An institutional registry was reviewed to identify patients undergoing standalone MMAE for symptomatic chronic/subacute subdural hematoma. Surgical rescue rate and time preceding 50% hematoma resolution were evaluated across 3 technical groups: aggressive penetration (AP), nonaggressive penetration with proximal coil embolization (NP-PC), and nonaggressive penetration alone (NP). Effect sizes were adjusted for demographic, neurological and radiological features through multivariable logistic and Cox regression. RESULTS: Among 117 procedures, 33.3% achieved AP, 36.8% had NP-PC, and 29.9% had NP. The rate of surgical rescue was 2.6% after AP, 9.3% for NP-PC, and 11.4% for NP. In patients not undergoing rescue surgery, 82.4% achieved hematoma resolution ≥50% at a median imaging follow-up of 56 days; AP or NP-PC were each statistically significantly associated with enhanced hematoma resolution as compared with NP (P = .02). Similarly, sensitivity analysis within medium-size hematoma and antiplatelet/anticoagulation-at-admission subgroups revealed a superiority of resolution after AP or NP-PC. A unique, comparative secondary analysis of liquid embolisate (Onyx vs n-butyl cyanoacrylate) revealed no impact on rate of surgical rescue or hematoma resolution. CONCLUSION: AP was associated with the lowest rate of surgical rescue, while both AP and NP-PC were associated with improved rates of hematoma resolution.

The management of dietary fiber intake in children with chronic kidney disease - clinical practice recommendations from the Pediatric Renal Nutrition Taskforce.

The benefits of dietary fiber are widely accepted. Nevertheless, a substantial proportion of children fail to meet the recommended intake of dietary fiber. Achieving adequate fiber intake is especially challenging in children with chronic kidney disease (CKD). An international team of pediatric renal dietitians and pediatric nephrologists from The Pediatric Renal Nutrition Taskforce (PRNT) has developed clinical practice recommendations (CPRs) for the dietary intake of fiber in children and adolescents with CKD. In this CPR paper, we propose a definition of fiber, provide advice on the requirements and assessment of fiber intake, and offer practical guidance on optimizing dietary fiber intake in children with CKD. In addition, given the paucity of available evidence and to achieve consensus from international experts, a Delphi survey was performed in which all the clinical practice recommendations were reviewed.

Distal Medium Vessel Occlusion Strokes: Understanding the Present and Paving the Way for a Better Future.

Distal medium vessel occlusions (DMVOs) are thought to cause as many as 25% to 40% of all acute ischemic strokes and may result in substantial disability amongst survivors. Although intravenous thrombolysis (IVT) is more effective for distal than proximal vessel occlusions, the overall efficacy of IVT remains limited in DMVO with less than 50% of patients achieving reperfusion and about 1/3 to 1/4 of the patients failing to achieve functional independence. Data regarding mechanical thrombectomy (MT) among these patients remains limited. The smaller, thinner, and more tortuous vessels involved in DMVO are presumably associated with higher procedural risks whereas a lower benefit might be expected given the smaller amount of tissue territory at risk. Recent advances in technology have shown promising results in endovascular treatment of DMVOs with room for future improvement. In this review, we discuss some of the key technical and clinical considerations in DMVO treatment including the anatomical and clinical terminology, diagnostic modalities, the role of IVT and MT, existing technology, and technical challenges as well as the contemporary evidence and future treatment directions.

Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI2 sponsored protocol: LION: A remote RCT protocol within VA.

Sleep-wake disturbances frequently present in Veterans with mild traumatic brain injury (mTBI). These TBI-related sleep impairments confer significant burden and commonly exacerbate other functional impairments. Therapies to improve sleep following mTBI are limited and studies in Veterans are even more scarce. In our previous pilot work, morning bright light therapy (MBLT) was found to be a feasible behavioral sleep intervention in Veterans with a history of mTBI; however, this was single-arm, open-label, and non-randomized, and therefore was not intended to establish efficacy. The present study, LION (light vs ion therapy) extends this preliminary work as a fully powered, sham-controlled, participant-masked randomized controlled trial (NCT03968874), implemented as fully remote within the VA (target n=120 complete). Randomization at 2:1 allocation ratio to: 1) active: MBLT (n=80), and 2) sham: deactivated negative ion generator (n=40); each with identical engagement parameters (60-min duration; within 2-hrs of waking; daily over 28-day duration). Participant masking via deception balanced expectancy assumptions across arms. Outcome measures were assessed following a 14-day baseline (pre-intervention), following 28-days of device engagement (post-intervention), and 28-days after the post-intervention assessment (follow-up). Primary outcomes were sleep measures, including continuous wrist-based actigraphy, self-report, and daily sleep dairy entries. Secondary/exploratory outcomes included cognition, mood, quality of life, circadian rhythm via dim light melatonin onset, and biofluid-based biomarkers. Participant drop out occurred in <10% of those enrolled, incomplete/missing data was present in <15% of key outcome variables, and overall fidelity adherence to the intervention was >85%, collectively establishing feasibility and acceptability for MBLT in Veterans with mTBI.

Electroencephalography-Guided Anesthesia and Delirium in Older Adults After Cardiac Surgery: The ENGAGES-Canada Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthesia decreases the incidence of delirium after cardiac surgery. Design, Setting, and Participants: Randomized, parallel-group clinical trial of 1140 adults 60 years or older undergoing cardiac surgery at 4 Canadian hospitals. Recruitment was from December 2016 to February 2022, with follow-up until February 2023. Interventions: Patients were randomized in a 1:1 ratio (stratified by hospital) to receive EEG-guided anesthesia (n = 567) or usual care (n = 573). Patients and those assessing outcomes were blinded to group assignment. Main Outcomes and Measures: The primary outcome was delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration and EEG suppression time. Secondary outcomes included intensive care and hospital length of stay. Serious adverse events included intraoperative awareness, medical complications, and 30-day mortality. Results: Of 1140 randomized patients (median [IQR] age, 70 [65-75] years; 282 [24.7%] women), 1131 (99.2%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 102 of 562 patients (18.15%) in the EEG-guided group and 103 of 569 patients (18.10%) in the usual care group (difference, 0.05% [95% CI, -4.57% to 4.67%]). In the EEG-guided group compared with the usual care group, the median volatile anesthetic minimum alveolar concentration was 0.14 (95% CI, 0.15 to 0.13) lower (0.66 vs 0.80) and there was a 7.7-minute (95% CI, 10.6 to 4.7) decrease in the median total time spent with EEG suppression (4.0 vs 11.7 min). There were no significant differences between groups in median length of intensive care unit (difference, 0 days [95% CI, -0.31 to 0.31]) or hospital stay (difference, 0 days [95% CI, -0.94 to 0.94]). No patients reported intraoperative awareness. Medical complications occurred in 64 of 567 patients (11.3%) in the EEG-guided group and 73 of 573 (12.7%) in the usual care group. Thirty-day mortality occurred in 8 of 567 patients (1.4%) in the EEG-guided group and 13 of 573 (2.3%) in the usual care group. Conclusions and Relevance: Among older adults undergoing cardiac surgery, EEG-guided anesthetic administration to minimize EEG suppression, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support EEG-guided anesthesia for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02692300.

Exploring Combat Tourniquet Application Errors and Duration Among Skilled and Novice Medical Trainees.

INTRODUCTION: The use of tourniquets in combat medicine continues to be a key focus as they have consistently been shown to combat one of the leading causes of preventable death on the battlefield, massive hemorrhage to extremities. The present study analyzed tourniquet application among combat medics (68W) and combat lifesavers (CLSs) in a training environment to determine whether trainees' performance is consistent among one another and whether performance can be associated with participant demographics such as experience or role. MATERIALS AND METHODS: Study participants treated male and female patient simulators within a tactical field care phase, both of which experienced an amputated leg and required the application of a Combat Application Tourniquet (CAT). To assess tourniquet application variability and performance, a series of application subtasks and potential errors were measured via video coding of the scenarios by a team of 5 coders. Time to tourniquet application and tourniquet application duration were also coded to assess correlations between application duration and variability or performance. RESULTS: Results from analyzing tourniquet application subtasks and errors through a series of one-way ANOVA tests showed that application of the CAT first, hasty CAT application, and high tourniquet application were not predictive of participant role, time within the role, and self-reported tourniquet skill, confidence, or experience. Such demographic variables were also not predictive of successful tourniquet application as defined by the number of windlass rod rotations. Results from binomial logistic regressions showed that participant role and self-reported tourniquet skill and experience were predictors of tourniquet application duration. CONCLUSION: The findings suggest that high variability in CAT application methodology and performance exists among CLS and combat medics, which is largely not predictable by various demographics such as role, experience within the designated role, and self-reported confidence, skill, or experience. The observed disconnect between training or experience and CAT application performance suggests substantial variability in the consistency of training for both CLS and 68W soldiers. These inconsistencies may stem from variability in instructor knowledge, teaching styles, or training materials or may be developed through informal methods such as experiences in the field or recommendations from colleagues and experts. These findings highlight a potential need to reassess CAT application training, particularly in regard to consistency and validation. Finally, it should be noted that the study's findings may be limited or fail to capture some study effects because of the sample size and wide range of reported experience among participants.

Interobserver agreement of peritoneal dialysis exit site scoring: Results from the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease (SCOPE) collaborative.

BACKGROUND: Exit site infections are a risk factor for the development of peritonitis in patients on long-term peritoneal dialysis. Visual assessments of an exit site utilising currently available tools (Twardowski and Mid-European Pediatric Peritoneal Dialysis Study Group (MEPPS)) are necessary to objectively characterise the appearance of an exit site. The aim of this study was to assess the interobserver agreement of exit site evaluations utilising both exit site scoring tools. METHODS: Exit site evaluations were independently performed by two evaluators during outpatient visits at 13 sites within the Standardizing Care to Improve Outcomes in Pediatric End Stage Kidney Disease collaborative. The frequency and percentage of evaluations where both reviewers agreed were calculated. A sub-analysis was performed looking at evaluations where disagreement occurred. RESULTS: A total of 371 paired exit site evaluations were collected over 6 months. For the majority of evaluations (range: 78%-97% Twardowski, 78%-97% MEPPS), both reviewers agreed that no abnormality was present across all domains. When the analysis was restricted to evaluations where at least one reviewer noted an abnormality, interobserver agreement fell across all domains (range: 31%-61% Twardowski, 56%-66% MEPPS). Disagreements more commonly occurred regarding the presence versus absence of an abnormality, rather than a difference in the severity of an abnormality. CONCLUSIONS: Whereas interobserver agreement is high when the appearance of a peritoneal dialysis catheter exit site is characterised as 'normal', interobserver disagreement is common when the appearance of the exit site is 'abnormal'. Further work is warranted to improve interobserver agreement of exit site assessments and to identify domains conferring an increased risk of infection.

Effect of Telemedicine Support for Intraoperative Anaesthesia Care on Postoperative Outcomes: The TECTONICS Randomised Clinical Trial.

Background: Novel applications of telemedicine can improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied. Methods: This single centre randomised clinical trial ( clinicaltrials.gov NCT03923699 ) of unselected adult surgical patients was conducted between July 1, 2019 and January 31, 2023. Patients received usual care or decision support from a telemedicine service, the Anesthesiology Control Tower (ACT). The ACT provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews, machine-learning forecasting, and physiologic alerts. ORs were randomised 1:1. Co-primary outcomes of 30-day all-cause mortality, respiratory failure, acute kidney injury (AKI), and delirium were analysed as intention-to-treat. Results: The trial completed planned enrolment with 71927 surgeries (35956 ACT; 35971 usual care). After multiple testing correction, there was no significant effect of the ACT vs. usual care on 30-day mortality [641/35956 (1.8%) vs 638/35971 (1.8%), risk difference 0.0% (95% CI -0.2% to 0.3%), p=0.96], respiratory failure [1089/34613 (3.1%) vs 1112/34619 (3.2%), risk difference -0.1% (95% CI -0.4% to 0.3%), p=0.96], AKI [2357/33897 (7%) vs 2391/33795 (7.1%), risk difference -0.1% (-0.6% to 0.4%), p=0.96], or delirium [1283/3928 (32.7%) vs 1279/3989 (32.1%), risk difference 0.6% (-2.0% to 3.2%), p=0.96]. There were no significant differences in secondary outcomes or in sensitivity analyses. Conclusions: In this large RCT of a novel application of telemedicine-based remote monitoring and decision support using real-time alerts and case reviews, we found no significant differences in postoperative outcomes. Large-scale intraoperative telemedicine is feasible, and we suggest future avenues where it may be impactful.

Understanding Staphylococcus aureus in hyperglycaemia: A review of virulence factor and metabolic adaptations.

Staphylococcus aureus is one of the most commonly detected bacteria in diabetic skin and soft tissue infections. The incidence and severity of skin and soft tissue infections are higher in patients with diabetes, indicating a potentiating mechanism of hyperglycaemia and infection. The goal of this review is to explore the metabolic and virulence factor adaptations of S. aureus under hyperglycaemic conditions. Primary data from identified studies were included and summarised in this paper. Understanding the nexus of hyperglycaemia, metabolism, and virulence factors provides insights into the complexity of diabetic skin and soft tissue infections attributed to S. aureus.

Prospective Study of Modifiable Risk Factors of Arterial Hypertension and Left Ventricular Hypertrophy in Pediatric Patients on Hemodialysis.

Introduction: Fluid and salt overload in patients on dialysis result in high blood pressure (BP), left ventricular hypertrophy (LVH) and hemodynamic instability, resulting in cardiovascular morbidity. Methods: Analysis of 910 pediatric patients on maintenance hemodialysis/hemodiafiltration (HD/HDF), prospectively followed-up with 2758 observations recorded every 6-months in the International Pediatric Hemodialysis Network (IPHN). Results: Uncontrolled hypertension was present in 55% of observations, with 27% of patients exhibiting persistently elevated predialysis BP. Systolic and diastolic age- and height-standardized BP (BP-SDS) were independently associated with the number of antihypertensive medications (odds ratio [OR] = 1.47, 95% confidence interval 1.39-1.56, 1.36 [1.23-1.36]) and interdialytic weight gain (IDWG; 1.19 [1.14-1.22], 1.09 [1.06-1.11]; all P < 0.0001). IDWG was related to urine output (OR = 0.27 [0.23-0.32]) and dialysate sodium (dNa; 1.06 [1.01-1.10]; all P < 0.0001). The prevalence of masked hypertension was 24%, and HD versus HDF use was an independent risk factor of elevated age- and height-standardized mean arterial pressure (MAP-SDS) (OR = 2.28 [1.18-4.41], P = 0.01). Of the 1135 echocardiograms, 51% demonstrated LVH. Modifiable risk factors included predialysis systolic BP-SDS (OR = 1.06 [1.04-1.09], P < 0.0001), blood hemoglobin (0.97 [0.95-0.99], P = 0.004), HD versus HDF modality (1.09 [1.02-1.18], P = 0.01), and IDWG (1.02 [1.02-1.03], P = 0.04). In addition, HD modality increased the risk of LVH progression (OR = 1.23 [1.03-1.48], P = 0.02). Intradialytic hypotension (IDH) was prevalent in patients progressing to LVH and independently associated with predialysis BP-SDS below 25th percentile, lower number of antihypertensives, HD versus HDF modality, ultrafiltration (UF) rate, and urine output, but not with dNa. Conclusion: Uncontrolled hypertension and LVH are common in pediatric HD, despite intense pharmacologic therapy. The outcome may improve with use of HDF, and superior anemia and IDWG control; the latter via lowering dNa, without increasing the risk of IDH.

Best Practice of Peritoneal Dialysis-Associated Gram-Negative Peritonitis in Children: Insights From the International Pediatric Peritoneal Dialysis Network Registry.

Introduction: Gram-negative peritonitis (GNP) is associated with significant morbidity in children receiving long-term peritoneal dialysis (PD) and current treatment recommendations are based on limited data. Methods: Analysis of 379 GNP episodes in 308 children (median age 6.9 years, interquartile range [IQR]: 3.0-13.6) from 45 centers in 28 countries reported to the International Pediatric Peritoneal Dialysis Network registry between 2011 and 2023. Results: Overall, 74% of episodes responded well to empiric therapy and full functional recovery (FFR) was achieved in 82% of cases. In vitro bacterial susceptibility to empiric antibiotics and lack of severe abdominal pain at onset were associated with a good initial response. Risk factors for failure to achieve FFR included severe abdominal pain at onset and at 60 to 72 hours from treatment initiation (odds ratio [OR]: 3.81, 95% confidence interval [CI]: 2.01-7.2 and OR: 3.94, 95% CI: 1.06-14.67, respectively), Pseudomonas spp. etiology (OR: 1.73, 95% CI: 1.71-4.21]) and in vitro bacterial resistance to empiric antibiotics (OR: 2.40, 95% CI: 1.21-4.79); the risk was lower with the use of monotherapy as definitive treatment (OR: 0.40, 95% CI: 0.21-0.77). Multivariate analysis showed no benefit of dual antibiotic therapy for treatment of Pseudomonas peritonitis after adjustment for age, presenting symptomatology, 60 to 72-hour treatment response, and treatment duration. Monotherapy with cefazolin in susceptible Enterobacterales peritonitis resulted in a similar FFR rate (91% vs. 93%) as treatment with ceftazidime or cefepime monotherapy. Conclusion: Detailed microbiological assessment, consisting of patient-specific and center-specific antimicrobial susceptibility data, should guide empiric treatment. Treatment "deescalation" with the use of monotherapy and narrow spectrum antibiotics according to susceptibility data is not associated with inferior outcomes and should be advocated in the context of emerging bacterial resistance.

CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza.

The high disease burden of influenza virus poses a significant threat to human health. Optimized diagnostic technologies that combine speed, sensitivity, and specificity with minimal equipment requirements are urgently needed to detect the many circulating species, subtypes, and variants of influenza at the point of need. Here, we introduce such a method using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform. Four SHINE assays were designed and validated for the detection and differentiation of clinically relevant influenza species (A and B) and subtypes (H1N1 and H3N2). When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously. This study demonstrates the utility of this duplex assay in discriminating two alleles of an oseltamivir resistance (H275Y) mutation as well as in simultaneously detecting influenza A and human RNAse P in patient samples. These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance.

HER2 overexpression in urothelial carcinoma with GATA3 and PPARG copy number gains.

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.

Incidence of Traumatic Brain Injuries within the Prehospital Trauma Registry System.

BACKGROUND: Traumatic brain injury (TBI) is often underreported or undetected in prehospital civilian and military settings. This study evaluated the incidence of TBI within the Prehospital Trauma Registry (PHTR) system. METHODS: We reviewed PHTR and the linked Department of Defense Trauma Registry (DoDTR) records of casualties from January 2003 through May 2019 for diagnostic data and surgical reports. RESULTS: A total of 709 casualties met inclusion criteria. The most common mechanism was blast, including 328 (51%) in the non-TBI and 45 (63%) in the TBI cohorts. The median injury severity scores in the non-TBI and TBI cohorts were 5 and 14, respectively. The survival scores in the non-TBI and TBI cohorts were 98% and 92%, respectively. Subdural hematomas, followed by subarachnoid hemorrhages were the most common classifiable brain injuries. Other nonspecific TBIs occurred in 85% of the TBI cohort casualties. Seventy-two cases (10%) were documented by the Role 1 clinician. Based on coding or operative data, 15 of the 72 (21%) were identified as TBIs. Of the 637 cases, which could not be decided based on coding or operative data, TBI was suspected in 42 (7%) cases based on Role 1 records. CONCLUSIONS: Over 1 in 10 casualties presenting to a Role 1 facility had a TBI requiring transfer to a higher level of care. Our findings suggest the need for improved diagnostic technologies and documentation systems at Role 1 facilities for accurate TBI diagnosis and reporting.