Derivation of a clinical decision rule for termination of resuscitation in non-traumatic pediatric out-of-hospital cardiac arrest.

AIM: Prehospital termination of resuscitation (ToR) rules are used to predict medical futility in adult out-of-hospital cardiac arrest (OHCA), however, the available evidence for pediatric patients is limited. The primary aim of this study is to derive a Pediatric Termination of Resuscitation (PToR) prediction rule for use in pediatric non-traumatic OHCA patients. METHODS: We analyzed a retrospective cohort of pediatric OHCA patients within the CARES database over a 10-year period (2013 - 2022). We split the dataset into training and test datasets and fit logistic regressions with Least Absolute Shrinkage and Selection Operator (LASSO) to select predictor variables and estimate predictive test characteristics for the primary outcome of death and a secondary composite outcome of death or survival to hospital discharge with unfavorable neurologic outcome. RESULTS: We analyzed a sample of 21,240 children where 2,326 (11.0%) survived to hospital discharge, and 1,894 (8.9%) survived to hospital discharge with favorable neurologic outcome. We derived a PToR rule for death demonstrating a specificity of 99.1% and a positive predictive value (PPV) of 99.8% and a PToR rule for death or survival with poor neurologic outcome with a specificity of 99.7% and PPV of 99.9% within the test dataset. CONCLUSION: We derived a clinical prediction rule with high specificity and positive predictive value in prehospital settings utilizing Advanced Life Support (ALS) providers which may inform termination of resuscitation considerations in pediatric patients. Further prospective and validation studies will be necessary to define the appropriateness and applicability of these PToR criteria for routine use.

Naloxone and Patient Outcomes in Out-of-Hospital Cardiac Arrests in California.

Importance: The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA. Objective: To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA. Design, Setting, and Participants: Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024. Exposure: EMS administration of naloxone. Main Outcomes and Measures: The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related. Results: Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77). Conclusions and Relevance: In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.

Fatal and non-fatal civilian injuries sustained during law enforcement-reported encounters in California, 2016-2021.

BACKGROUND: In 2015, California passed AB 71 to create a state-wide Use of Force Incident Reporting Database (URSUS) to tabulate law enforcement-reported encounters that resulted in serious bodily injury, death or discharge of a firearm. We use these data to analyse encounters that resulted in fatal and non-fatal civilian injuries in California between 2016 and 2021. METHODS: We performed a retrospective review of URSUS from January 2016 to December 2021. The main outcomes were the number of law enforcement encounters that involved civilian serious bodily injury or death and encounter-level characteristics. RESULTS: URSUS recorded 3677 incidents between 2016 and 2021 resulting in 942 civilian fatalities and 2735 instances of serious civilian injuries. Injury rates were highest for civilians who identified as Hispanic (1.80 injuries per 100 000 population) or black (5.17 injuries per 100 000 population). Injuries involving a firearm were usually fatal (58.9% fatality rate; 1471 injuries), while non-firearm incidents were more likely to result in serious injuries (4.2% fatality rate; 2929 injuries). We did not find statistically significant trends in rates of civilian injuries per 100 000 population. CONCLUSION: Rates of law enforcement-related injuries were highest for Hispanic and black civilians in California between 2016 and 2021 and firearm-related injuries were overwhelmingly fatal. The URSUS database represents an important effort by law enforcement agencies to collect information on injuries and fatalities resulting from law enforcement encounters. Given similar databases exist in fewer than half of states, additional legislative efforts are needed to improve systematic national data collection on these encounters.

Associations between long-term exposure to air pollution and kidney function utilizing electronic healthcare records: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) affects more than 38 million people in the United States, predominantly those over 65 years of age. While CKD etiology is complex, recent research suggests associations with environmental exposures. METHODS: Our primary objective is to examine creatinine-based estimated glomerular filtration rate (eGFRcr) and diagnosis of CKD and potential associations with fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) using a random sample of North Carolina electronic healthcare records (EHRs) from 2004 to 2016. We estimated eGFRcr using the serum creatinine-based 2021 CKD-EPI equation. PM2.5 and NO2 data come from a hybrid model using 1 km2 grids and O3 data from 12 km2 CMAQ grids. Exposure concentrations were 1-year averages. We used linear mixed models to estimate eGFRcr per IQR increase of pollutants. We used multiple logistic regression to estimate associations between pollutants and first appearance of CKD. We adjusted for patient sex, race, age, comorbidities, temporality, and 2010 census block group variables. RESULTS: We found 44,872 serum creatinine measurements among 7,722 patients. An IQR increase in PM2.5 was associated with a 1.63 mL/min/1.73m2 (95% CI: -1.96, -1.31) reduction in eGFRcr, with O3 and NO2 showing positive associations. There were 1,015 patients identified with CKD through e-phenotyping and ICD codes. None of the environmental exposures were positively associated with a first-time measure of eGFRcr < 60 mL/min/1.73m2. NO2 was inversely associated with a first-time diagnosis of CKD with aOR of 0.77 (95% CI: 0.66, 0.90). CONCLUSIONS: One-year average PM2.5 was associated with reduced eGFRcr, while O3 and NO2 were inversely associated. Neither PM2.5 or O3 were associated with a first-time identification of CKD, NO2 was inversely associated. We recommend future research examining the relationship between air pollution and impaired renal function.

Trends in presumed drug overdose out-of-hospital cardiac arrests in San Francisco, 2015-2023.

INTRODUCTION: Estimates of the prevalence of drug-related out of hospital cardiac arrest (OHCA) vary, ranging from 1.8% to 10.0% of medical OHCA. However, studies conducted prior to the recent wave of fentanyl deaths likely underestimate the current prevalence of drug-related OHCA. We evaluated recent trends in drug-related OHCA, hypothesizing that the proportion of presumed drug-related OHCA treated by emergency medical services (EMS) has increased since 2015. METHODS: We conducted a retrospective analysis of OHCA patients treated by EMS providers in San Francisco, California between 2015 and 2023. Participants included OHCA cases in which resuscitation was attempted by EMS. The study exposure was the year of arrest. Our primary outcome was the occurrence of drug-related OHCA, defined as the EMS impression of OHCA caused by a presumed or known overdose of medication(s) or drug(s). RESULTS: From 2015 to 2023, 5044 OHCA resuscitations attended by EMS (average 561 per year) met inclusion criteria. The median age was 65 (IQR 50-79); 3508 (69.6%) were male. The EMS impression of arrest etiology was drug-related in 446/5044 (8.8%) of OHCA. The prevalence of presumed drug-related OHCA increased significantly each year from 1% in 2015 to 17.6% in 2023 (p-value for trend = 0.0001). After adjustment, presumed drug-related OHCA increased by 30% each year from 2015-2023. CONCLUSION: Drug-related OHCA is an increasingly common etiology of OHCA. In 2023, one in six OHCA was presumed to be drug related. Among participants less than 60 years old, one in three OHCA was presumed to be drug related.

Phenobarbital treatment of alcohol withdrawal in the emergency department: A systematic review and meta-analysis.

OBJECTIVE: Despite frequent treatment of alcohol withdrawal syndrome (AWS) in the emergency department (ED), evidence for phenobarbital (PB) as an ED alternative therapy is mixed. We conducted a systematic review and meta-analysis comparing safety and efficacy of PB to benzodiazepines (BZDs) for treatment of AWS in the ED. METHODS: We searched articles and references published in English in PubMed, Web of Science, and Embase from inception through May 2022. We included randomized trials and cohort studies comparing treatment with PB to BZD controls and excluded studies focused on non-AWS conditions. Review was conducted by two blinded investigators and a third author; eight of 59 (13.6%) abstracts met inclusion criteria for review and meta-analysis using a random-effects model. Treatment superiority was evaluated through utilization, pharmacologic, and clinical outcomes. Primary outcomes for meta-analysis were the proportion of patients (1) admitted to the intensive care unit (ICU), (2) admitted to the hospital, (3) readmitted to the ED after discharge, and (4) who experienced adverse events. RESULTS: Eight studies (two randomized controlled trials, six retrospective cohorts) comprised data from 1507 patients in 2012 treatment encounters for AWS. All studies were included in meta-analysis for adverse events, seven for hospital admission, five for ICU admission, and three for readmission to the ED after discharge. Overall methodological quality was low-moderate, risk of bias moderate-high, and statistical heterogeneity moderate. Pooled relative risk of ICU admission for those treated with PB versus BZD was 0.92 (95% confidence interval [CI] 0.54-1.55). Risk for admission to the hospital was 0.98 (95% CI 0.89-1.07) and for any adverse event was 1.1 (95% CI 0.78-1.57); heterogeneity prevented meta-analysis for ED readmission. CONCLUSIONS: The current literature base does not show that treatment with PB significantly reduces ICU admissions, hospital admissions, ED readmissions, or adverse events in ED patients with AWS compared with BZDs alone.

Racial Disparities in Emergency Department Physical Restraint Use: A Systematic Review and Meta-Analysis.

Importance: Recent studies have demonstrated that people of color are more likely to be restrained in emergency department (ED) settings compared with other patients, but many of these studies are based at a single site or health care system, limiting their generalizability. Objective: To synthesize existing literature on risk of physical restraint use in adult EDs, specifically in reference to patients of different racial and ethnic backgrounds. Data Sources: A systematic search of PubMed, Embase, Web of Science, and CINAHL was performed from database inception to February 8, 2022. Study Selection: Included peer-reviewed studies met 3 criteria: (1) published in English, (2) original human participants research performed in an adult ED, and (3) reported an outcome of physical restraint use by patient race or ethnicity. Studies were excluded if they were conducted outside of the US, or if full text was unavailable. Data Extraction and Synthesis: Four independent reviewers (V.E., M.M., D.D., and A.H.) abstracted data from selected articles following Meta-Analysis of Observational Studies in Epidemiology guidelines. A modified Newcastle-Ottawa scale was used to assess quality. A meta-analysis of restraint outcomes among minoritized racial and ethnic groups was performed using a random-effects model in 2022. Main Outcome(s) and Measure(s): Risk of physical restraint use in adult ED patients by racial and ethnic background. Results: The search yielded 1597 articles, of which 10 met inclusion criteria (0.63%). These studies represented 2 557 983 patient encounters and 24 030 events of physical restraint (0.94%). In the meta-analysis, Black patients were more likely to be restrained compared with White patients (RR, 1.31; 95% CI, 1.19-1.43) and to all non-Black patients (RR, 1.27; 95% CI, 1.23-1.31). With respect to ethnicity, Hispanic patients were less likely to be restrained compared with non-Hispanic patients (RR, 0.85; 95% CI, 0.81-0.89). Conclusions and Relevance: Physical restraint was uncommon, occurring in less than 1% of encounters, but adult Black patients experienced a significantly higher risk of physical restraint in ED settings compared with other racial groups. Hispanic patients were less likely to be restrained compared with non-Hispanic patients, though this observation may have occurred if Black patients, with a higher risk of restraint, were included in the non-Hispanic group. Further work, including qualitative studies, to explore and address mechanisms of racism at the interpersonal, institutional, and structural levels are needed.

Efficacy of emergency department calcium administration in cardiac arrest: A 9-year retrospective evaluation.

BACKGROUND: The efficacy of empiric calcium for patients with undifferentiated cardiac arrest has come under increased scrutiny, including a randomized controlled trial that was stopped early due to a trend towards harm with calcium administration. However, small sample sizes and non-significant findings have hindered precise effect estimates. In this analysis we evaluate the association of calcium administration with survival in a large retrospective cohort of patients with cardiac arrest treated in the emergency department (ED). METHODS: We conducted a retrospective review of medical records from two academic hospitals (one quaternary care center, one county trauma center) in San Francisco between 2011 and 2019. Inclusion criteria were patients aged greater than or equal to 18 years old who received treatment for cardiac arrest during their ED course. Our primary exposure was the administration of calcium while in the ED and the main outcome was survival to hospital admission. The association between calcium and survival to admission was estimated using a multivariable log-binomial regression, and also with two propensity score models. RESULTS: We examined 781 patients with cardiac arrest treated in San Francisco EDs between 2011 and 2019 and found that calcium administration was associated with decreased survival to hospital admission (RR 0.74; 95% CI 0.66-0.82). These findings remained significant after adjustment for patient age, sex, whether the cardiac arrest was witnessed, and including an interaction term for shockable cardiac rhythms (RR 0.60; 95% CI 0.50-0.72) and non-shockable cardiac rhythms (RR 0.87; 95% CI 0.76-0.99). Risk ratios for the association between calcium and survival to hospital admission were also similar between two propensity score-based models: nearest neighbor propensity matching model (RR 0.79; 95% CI 0.68-0.89) and inverse propensity weighted regression adjustment model (RR 0.75; 95% CI 0.67-0.84). CONCLUSIONS: Calcium administration as part of ED-directed treatment for cardiac arrest was associated with lower survival to hospital admission. Given the lack of statistically significant outcomes from smaller, more methodologically robust evaluations on this topic, we believe these findings have an important role to serve in confirming previous results and allowing for more precise effect estimates. Our data adds to the growing body evidence against the empiric use of calcium in cardiac arrest.

Effect of an ultrasound-first clinical decision tool in emergency department patients with suspected nephrolithiasis: A randomized trial.

INTRODUCTION: Previously, we found that the use of ultrasonography for patients with suspected nephrolithiasis resulted in similar outcomes and less radiation exposure vs. CT scan. In this study, we evaluated the implementation of an ultrasound-first clinical decision support (CDS) tool in patients with suspected nephrolithiasis. METHODS: This randomized trial was conducted at an academic emergency department (ED). We implemented the ultrasound-first CDS tool, deployed when an ED provider placed a CT order for suspected nephrolithiasis. Providers were randomized to receiving the CDS tool vs. usual care. The primary outcome was receipt of CT during the index ED visit. Secondary outcomes included radiation dose and ED revisit. RESULTS: 64 ED Providers and 254 patients with suspected nephrolithiasis were enrolled from January 2019 through Dec 2020. The US-First CDS tool was deployed for 128 patients and was not deployed for 126 patients. 86.7% of patients in the CDS arm received a CT vs. 94.4% in the usual care arm, resulting in an absolute risk difference of -7.7% (-14.8 to -0.6%). Mean radiation dose in the CDS arm was 6.8 mSv (95% CI 5.7-7.9 mSv) vs. 6.1 mSv (95% CI 5.1-7.1 mSv) in the usual care arm. The CDS arm did not result in increased ED revisits, CT scans, or hospitalizations at 7 or 30 days. CONCLUSIONS AND RELEVANCE: Implementation of the US-first CDS tool resulted in lower CT use for ED patients with suspected nephrolithiasis. The use of this decision support may improve the evaluation of a common problem in the ED. TRIAL REGISTRATION: ClinicalTrials.gov#NCT03461536.

Post-operative Horner's Syndrome: A Rare Complication Following Posterior Scoliosis Surgery in a Patient With Syringomyelia.

Horner's syndrome following posterior spinal instrumentation for scoliosis has been rarely reported. We describe the case of a 15-year-old male who presented with right-sided ptosis, miosis, and anhidrosis after scoliosis correction. This is the first reported case of first-order Horner's syndrome developing after scoliosis repair via posterior fixation in a patient known to have asymptomatic syringomyelia. The impression was that Horner's syndrome developed secondary to increased traction of the syringomyelia after scoliosis repair. This is significant as a diagnosis of Horner's syndrome can be distressing to patients and chronic cases cause cosmetic defects that might require surgical correction. We suggest that similar patients should be warned pre-operatively given the psychological distress associated with chronic Horner's syndrome. This case also illustrates the importance of an appropriate workup to rule out other sinister pathologies that can cause Horner's syndrome.

Bilateral recurrent laryngeal nerve palsy following anterior cervical surgery subsequent to contralateral apical lung radiotherapy.

Unilateral recurrent laryngeal nerve palsy is a potential complication of the anterior approach for cervical surgery. It is a rare complication of radiotherapy to the neck. Only one case has been reported following radiotherapy apical lung cancer. It can result in unilateral vocal cord paralysis. We report a patient who demonstrated bilateral vocal cord paralysis immediately following right-sided anterior cervical surgery, with significant consequences, including aphonia, respiratory distress and subsequent takotsubo cardiomyopathy. She was diagnosed with acute, (temporary) post-operative right recurrent laryngeal nerve palsy, on the background of undetected and previously asymptomatic left recurrent laryngeal nerve palsy following radiotherapy for left apical lung cancer. The possibility of recurrent laryngeal nerve palsy should be considered in patients with previous apical lung cancer and/ or radiotherapy. Patents undergoing subsequent anterior cervical surgery should be considered for the appropriate precautions in the form of same-side surgery or pre-operative investigation for vocal cord paralysis.

Contributions of biomass/solid fuel burning to blood pressure modification in women: A systematic review and meta-analysis.

OBJECTIVES: Approximately 2½ billion people worldwide rely on solid/biomass fuel as fuel for cooking/heating the home. Environmental exposure to the smoke associated with biomass fuel burning has been associated respiratory diseases, cardiac disorders, and altered blood pressure. Therefore, a systematic review and meta-analysis was conducted to study this relationship across multiple studies. METHODS: Searches were performed using PRISMA guidelines for articles using Web of Science, PubMed, Toxline, and Web of Science of peer reviewed papers with no beginning time restriction until February 2017. The search yielded 10 manuscripts after application of inclusion criteria, which encompassed 93 724 participants. Outcomes included (a) the proportion of people with a clinical diagnosis of hypertension in an exposed (vs. unexposed) population or (b) correlation coefficients examining degree of exposure and systolic/diastolic blood pressure. RESULTS: The four studies reporting effect sizes for hypertension (N = 92 042) had a weighted mean effect size of r = .12 [-0.02, 0.27], z = 1.66, p = 0.097. The six studies reporting effect sizes for systolic and diastolic blood pressure (N = 1682) had weighted mean effect sizes of r = .15 [0.06, 0.24], p = 0.001, and r = .09 [0.03, 0.15], p = 0.002, respectively. CONCLUSION: These analyses revealed that there is a small-but-significant relationship between biomass fuel exposure and an increase in both systolic and diastolic blood pressure, but the relationship between biomass fuel and hypertension specifically remains unclear.

Development of a lupus nephritis suboptimal response prediction tool using renal histopathological and clinical laboratory variables at the time of diagnosis.

OBJECTIVE: Lupus nephritis (LN) is an immune complex-mediated glomerular and tubulointerstitial disease in patients with SLE. Prediction of outcomes at the onset of LN diagnosis can guide decisions regarding intensity of monitoring and therapy for treatment success. Currently, no machine learning model of outcomes exists. Several outcomes modelling works have used univariate or linear modelling but were limited by the disease heterogeneity. We hypothesised that a combination of renal pathology results and routine clinical laboratory data could be used to develop and to cross-validate a clinically meaningful machine learning early decision support tool that predicts LN outcomes at approximately 1 year. METHODS: To address this hypothesis, patients with LN from a prospective longitudinal registry at the Medical University of South Carolina enrolled between 2003 and 2017 were identified if they had renal biopsies with International Society of Nephrology/Renal Pathology Society pathological classification. Clinical laboratory values at the time of diagnosis and outcome variables at approximately 1 year were recorded. Machine learning models were developed and cross-validated to predict suboptimal response. RESULTS: Five machine learning models predicted suboptimal response status in 10 times cross-validation with receiver operating characteristics area under the curve values >0.78. The most predictive variables were interstitial inflammation, interstitial fibrosis, activity score and chronicity score from renal pathology and urine protein-to-creatinine ratio, white blood cell count and haemoglobin from the clinical laboratories. A web-based tool was created for clinicians to enter these baseline clinical laboratory and histopathology variables to produce a probability score of suboptimal response. CONCLUSION: Given the heterogeneity of disease presentation in LN, it is important that risk prediction models incorporate several data elements. This report provides for the first time a clinical proof-of-concept tool that uses the five most predictive models and simplifies understanding of them through a web-based application.

Screening performance of the chest X-ray in adult blunt trauma evaluation: Is it effective and what does it miss?

BACKGROUND: Although chest x-ray (CXR) is often used as a screening tool for thoracic injury in adult blunt trauma assessment, its screening performance is unclear. Using chest CT as the referent standard, we sought to determine the screening performance of CXR for injury. METHODS: We analyzed data from the NEXUS Chest CT study, in which we prospectively enrolled blunt trauma patients older than 14 years who received chest imaging as part of their evaluation at nine level I trauma centers. For this analysis, we included patients who had both CXR and chest CT. We used CT as the referent standard and categorized injuries as clinically major or minor according to an a priori expert panel classification. RESULTS: Of 11,477 patients enrolled, 4501 had both CXR and chest CT; 1496 (33.2%) were found to have injury, of which 256 (17%) were classified as major injury. CXR missed injuries in 818 patients (54.7%), of which 63 (7.7%) were classified as major injuries. For injuries of major clinical significance, CXR had a sensitivity of 75.4% (95% confidence interval [CI] 69.6-80.4%), specificity of 86.2% (95% CI 85.1-87.2%), negative predictive value of 98.3 (95%CI 97.9-98.6%), and positive predictive value of 24.7 (95%CI 22.9-26.7%). For any injury CXR had a sensitivity of 45.3% (95% CI 42.8-47.9%), specificity of 96.6% (95% CI 95.9-97.2%), negative predictive value of 78% (95% CI 77.2-78.8%), and positive predictive value of 86.9% (95% CI 84.5-89.0%). The most common missed major injuries were pneumothorax (30/185; 16.2%), spinal fractures (19/39; 48.7%), and hemothorax (8/70; 11.4%). The most common missed minor injuries were rib fractures (381/836; 45.6%), pulmonary contusion (203/462; 43.9%), and sternal fractures (153/229; 66.8%). CONCLUSIONS: When used alone, without other trauma screening criteria, CXR has poor screening performance for blunt thoracic injury.

Gastrointestinal dysbiosis following diethylhexyl phthalate exposure in zebrafish (Danio rerio): Altered microbial diversity, functionality, and network connectivity.

Microbiome community structure is intimately involved in key biological functions in the gastrointestinal (GI) system including nutrient absorption and lipid metabolism. Recent evidence suggests that disruption of the GI microbiome is a contributing factor to metabolic disorders and obesity. Poor diet and chemical exposure have been independently shown to cause disruption of the GI microbiome community structure and function. We hypothesized that the addition a chemical exposure to overfeeding exacerbates adverse effects on the GI microbiome community structure and function. To test this hypothesis, adult zebrafish were fed a normal feeding regime (Control), an overfeeding regime (OF), or an overfeeding regime contaminated with diethylhexyl phthalate (OF + DEHP), a suspected obesogen-inducing chemical. After 60 days, fecal matter was collected for sequencing, identification, and quantification of the GI microbiome using the 16s rRNA hypervariable region. Analysis of beta diversity indicated distinct microbial profiles between treatments with the largest divergence between Control and OF + DEHP groups. Based upon functional predictions, OF + DEHP treatment altered carbohydrate metabolism, while both OF and OF + DEHP affected biosynthesis of fatty acids and lipid metabolism. Co-occurrence network analysis revealed decreases in cluster size and a fracturing of the microbial community network into unconnected components and a loss of keystone species in the OF + DEHP treatment when compared to Control and OF treatments. Data suggest that the addition of DEHP in the diet may exacerbate microbial dysbiosis, a consequence that may explain in part its role as an obesogenic chemical.

Proximal junctional kyphosis and rates of fusion following posterior instrumentation and spinal fusion for adolescent idiopathic scoliosis.

BACKGROUND: Proximal junctional kyphosis (PJK) can cause significant functional impairment and neural compression. Varying rates of PJK and pseudoarthrosis following posterior instrumentation and fusion for adolescent idiopathic scoliosis (AIS) are described with multiple biologic and biomechanical correlations attributed. This retrospective study aims to determine our rate of pseudoarthrosis and PJK in posterior spinal fusion for AIS, along with analysing the influence of autograft and allograft bone volume. METHODS: Immediate and 12-month post-operative radiographs of 78 patients treated for AIS were analysed along with late complications to a minimum of 2 years. Proximal kyphosis was determined by measuring and comparing the angle between the upper instrumented vertebra and upper instrumented vertebra + 2 for both immediate and 12-month post-operative radiographs. Spinal fusion was determined using an accepted grading scale on the 12-month radiograph. These findings were correlated with known surgical variables in bone grafting technique. RESULTS: There was one case of PJK and no cases of pseudoarthrosis. Three patients showed a defect in the fusion mass but were still suggestive of fusion. The rates of fusion and PJK were not significantly different when using different allograft volumes or incorporating autograft. CONCLUSION: Relatively low rates of PJK following AIS correction were observed compared to the literature. Rates were not increased with the use of proximal autograft. The amount of allograft used did not affect fusion rates either.

Intraoperative neurophysiology monitoring in scoliosis surgery in children.

OBJECTIVE: Intraoperative neurophysiology monitoring (INM) is thought to reduce the risk of postoperative neurological deficits in children undergoing scoliosis and spine deformity surgery. INM is being used increasingly despite conflicting opinions, varied results, non-standard alarm criteria and concern regarding cost effectiveness. In this paper we present our experience with INM in scoliosis and spine deformation surgery in children, propose alert criteria and preferred anaesthetics in clinical practice. METHODS: We retrospectively analysed our experience with INM in 56 children who had 61 scoliosis and spine deformity surgeries. RESULTS: INM was successfully undertaken with transcranial electrical motor evoked potentials (TcMEP) and somatosensory evoked potentials. There were no injuries due to INM. Four children had 5 alerts during 4 surgeries. A postoperative deficit was seen in one child only. No new postoperative deficits were seen in any child who did not have an alert during INM. Total intravenous anaesthesia was better for INM compared to inhalational anaesthetics. CONCLUSIONS: INM is useful in scoliosis surgery; it is likely to mitigate the risk of new deficits following surgery. We recommend alert criteria for TcMEPs that include multiple facets - amplitude, stimulus paradigm, morphology. We recommend propofol and remifentanil, in preference to sevoflurane and remifentanil for anaesthesia during INM. SIGNIFICANCE: Our study adds to the literature supporting the role of INM in scoliosis surgery in children. We provide guidelines for alarm criteria in clinical practice and recommend the use of total intravenous anaesthesia as the preferred anaesthetic option.

HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

BACKGROUND: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. METHODS: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. FINDINGS: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. INTERPRETATION: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.