Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with ...increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis.
We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p < 0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites.
We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range IQR 36 to 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL IQR 67 to 336 ng/dL in those who did (p < 0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis.
Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.
The world's most catastrophic epidemic thunderstorm asthma event (ETSA) affected Melbourne in 2016. Little is known about the natural history of individuals affected by such extreme events.
In this ...single center prospective 3-year longitudinal study, symptomatology and behaviors of individuals affected by ETSA were assessed.
Standardized telephone questionnaire was used to evaluate frequency of asthma symptoms, inhaled corticosteroid preventer use, asthma action plan ownership, and healthcare utilization. Questionnaires were administered at 12, 24, and 36 months after 2016 ETSA. Subgroup analyses of the 'current', 'past', 'possible,' and 'no asthma' subgroups were also conducted.
Two hundred and eight, 164, and 112 completed questionnaires were analyzed in 2017, 2018, and 2019, respectively. Seventy to eighty five percent of respondents reported ongoing asthma symptoms in any given year, of which 20%-28% experienced weekly symptoms. Nearly 50% of respondents were prescribed preventers, with approximately 45% adherent at least 5 days a week. Less than 40% had an asthma action plan and 15%-20% sought urgent medical attention for asthma over the follow-up period. Among 106 individuals with 3 consecutive years of completed questionnaires, those with no prior doctor diagnosis of asthma were significantly more likely to be asymptomatic on follow-up than those with a prior doctor diagnosis of asthma (
= 0.02). Subgroup analyses suggest that large proportions of respondents with 'past' and 'no asthma' continue to remain symptomatic throughout the 36-month period.
In individuals affected by ETSA, we found evidence of ongoing loss of asthma control in those with previously well controlled asthma, and the persistence of symptoms suggestive of asthma in those with no history or symptoms suggestive of prior asthma, even after 36 months from initial ETSA. Low rates of inhaler adherence and asthma action plan ownership may contribute to increased morbidity and mortality from future ETSA events. Further research is required to confirm these findings.
Mandibular and medial retropharyngeal lymph nodes are routinely evaluated with CT when staging dogs with oral melanomas. While size alone is considered inadequate for detecting nodal metastasis, it ...is critical in evaluating treatment response, as clinical decisions are based on changes in size. It is common for different radiologists to measure the size of pre‐ and posttreatment lymph nodes in the same patient. The objective of this retrospective, observer agreement study was to evaluate the inter‐ and intraobserver agreement in measuring canine mandibular and medial retropharyngeal lymph nodes by a diverse population of veterinary radiologists and trainees. Fourteen dogs with documented oral melanoma and head CT studies identified from records of a single institution were included in this study. North American veterinary radiologists and trainees were recruited to measure the mandibular and medial retropharyngeal lymph nodes; in triplicate. Prior to performing the study measurements, participants completed a training tool demonstrating the lymph node measurements. Overall, interobserver intraclass correlation coefficient (ICC) was 0.961 (95% confidence interval CI: 0.946, 0.972) and intraobserver ICC was 0.977 (95% CI: 0.968, 0.983), indicating excellent agreement (ICC > 0.9 considered excellent). Similar findings were noted following sub‐analysis for most variables (experience, size, laterality, axis of measurement). These results suggest that follow‐up measurement of the long and short axis of the mandibular lymph nodes and short axis of the medial retropharyngeal lymph nodes in the transverse plane, performed by different veterinary radiologists using the same method of measure, should have minimal impact on clinical decision making.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) 2-question screen is a valid adolescent alcohol screening tool. No studies have examined if this tool predicts future alcohol problems. ...We conducted a study at 16 pediatric emergency departments to determine the tool's predictive validity for alcohol misuse and alcohol use disorders (AUDs).
Participants (
= 4834) completed a baseline assessment battery. A subsample of participants completed the battery at 1, 2, and 3 years follow up.
Of the 2209 participants assigned to follow-up, 1611 (73%) completed a 1-year follow-up, 1591 (72%) completed a 2-year follow-up, and 1377 (62%) completed a 3-year follow-up. The differences in AUDs between baseline NIAAA screen nondrinkers and lower-risk drinkers were statistically significant at 1 year (
= .0002), 2 years (
<.0001), and 3 years (
= .0005), as were the differences between moderate- and highest-risk drinkers at 1 and 2 years (
< .0001 and
= .0088, respectively) but not at 3 years (
= .0758). The best combined score for sensitivity (86.2% at 1 year, 75.6% at 2 years, and 60.0% at 3 years) and specificity (78.1% at 1 year, 79.2% at 2 years, and 80.0% at 3 years) was achieved by using "lower risk" and higher as a cutoff for the prediction of a
diagnosis.
The NIAAA 2-question screen can accurately characterize adolescent risk for future AUDs. Future studies are needed to determine optimaluse of the screen.
We report the discovery of a second western Atlantic brackish-coastal cochliopid gastropod in San Francisco Bay Spurwinkia salsa (Pilsbry, 1905), and detail the first records for a widely distributed ...member of the family, Tryonia porrecta (Mighels, 1845), from artificial lakes (in the Phoenix metropolitan area). These identifications were based on morphological criteria and supported by mitochondrial DNA sequence data that also indicates little or no divergence of the newly reported populations, which is consistent with evolutionarily recent spread or separation. Spurwinkia salsa was most likely introduced to San Francisco Bay either in recent decades in bait worm packing or ships' ballast or in the 19 super(th) or early 20 super(th) century in solid ballast or with oyster imports. The discovery of T. porrecta in artificial lakes in the Phoenix area in 1984 and 2014 may be due to either recent arrival in the area or to dispersal into a newly available habitat from a population long present in the area. In either case, the occurrence of T. porrecta in the Phoenix area is likely due to transport on birds along an eastern branch of the Pacific Flyway. The discovery of T. porrecta in artificial lakes suggests that this species (which is typically distributed in thermal springs) is more broadly tolerant than previously thought. Additional spread of this unusual snail within the highly modified aquatic ecosystem of the Phoenix metropolitan area (which includes more than 900 artificial lakes) would appear likely.
Morbidly obese patients who accomplish substantial weight loss often display a long-term decline in their resting metabolism, causing even relatively restrained caloric intake to trigger a relapse to ...the obese state. Paradoxically, we observed that morbidly obese mice receiving chemotherapy for cancer experienced spontaneous weight reduction despite unabated ingestion of their high fat diet (HFD). This response to chemotherapy could also be achieved in morbidly obese mice without cancer. Optimally dosed methotrexate (MTX) or cyclophosphamide (CY) enabled the mice to completely and safely normalize their body weight despite continued consumption of obesogenic quantities of HFD. Weight reduction was not attributable to decreased HFD intake, enhanced energy expenditure or malabsorption. MTX or CY dosing significantly depleted both adipose tissue and preadipocyte progenitors. Remarkably, however, despite continued high fat feeding, a compensatory increase in hepatocyte lipid storage was not observed, but rather the opposite. Gene microarray liver analyses demonstrated that HFD mice receiving MTX or CY experienced significantly inhibited lipogenesis and lipid storage, whereas Enho (energy homeostasis) gene expression was significantly upregulated. Further metabolic studies employing a human hepatocellular line revealed that MTX treatment preserved robust oxidative phosphorylation, but also promoted mitochondrial uncoupling with a surge in proton leak. This is the first report that certain optimally dosed chemotherapeutic agents can induce weight loss in morbidly obese mice without reduced dietary intake, apparently by depleting stores of adipocytes and their progenitors, curtailment of lipogenesis, and inconspicuous disposal of incoming dietary lipid via a steady state partial uncoupling of mitochondrial oxidative phosphorylation.
IMPORTANCE: The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. OBJECTIVE: To examine the association of fetal ASM exposure with ...subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. DESIGN, SETTING, AND PARTICIPANTS: The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. EXPOSURES: Exposures included mother’s epilepsy status as well as mother’s ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. MAIN OUTCOMES AND MEASURES: The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. RESULTS: Primary analysis included 302 children of women with epilepsy (143 boys 47.4%) and 84 children of women without epilepsy (45 boys 53.6%). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate PE, 0.4 95% CI, −2.5 to 3.4; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, −7.8 95% CI, −12.6 to −3.1; P = .001). This decrease in functioning was evident for levetiracetam (PE, −18.9 95% CI, −26.8 to −10.9; P < .001) and lamotrigine (PE, −12.0 95% CI, −23.7 to −0.3; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. CONCLUSIONS AND RELEVANCE: This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.
ABSTRACT
Aims The primary aim was to compare the efficacy of smoking cessation treatment using a combination of active nicotine patch plus active nicotine gum versus therapy consisting of active ...nicotine patch plus placebo gum in a sample of alcohol‐dependent tobacco smokers in an early phase of out‐patient alcohol treatment. A secondary aim was to determine whether or not there were any carry‐over effects of combination nicotine replacement on drinking outcomes.
Design Small‐scale randomized double‐blind placebo‐controlled clinical trial with 1‐year smoking and drinking outcome assessment.
Setting Two out‐patient substance abuse clinics provided a treatment platform of behavioral alcohol and smoking treatment delivered in 3 months of weekly sessions followed by three monthly booster sessions.
Participants Participants were 96 men and women with a diagnosis of alcohol abuse or dependence and smoking 15 or more cigarettes per day.
Intervention All participants received open‐label transdermal nicotine patches and were randomized to receive either 2 mg nicotine gum or placebo gum under double‐blind conditions.
Findings Analysis of 1‐year follow‐up data revealed that patients receiving nicotine patch plus active gum had better smoking outcomes than those receiving patch plus placebo gum on measures of time to smoking relapse and prolonged abstinence at 12 months. Alcohol outcomes were not significantly different across medication conditions.
Conclusions Results of this study were consistent with results of larger trials of smokers without alcohol problems, showing that combination therapy (nicotine patch plus gum) is more effective than monotherapy (nicotine patch) for smoking cessation.
Recent studies have demonstrated the value of ancillary techniques, including p57 immunohistochemistry and short tandem repeat genotyping, for distinguishing hydatidiform moles (HM) from nonmolar ...specimens and for subtyping HMs as complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM). With rare exceptions, CHMs are p57-negative and androgenetic diploid; partial hydatidiform moles are p57-positive and diandric triploid; and nonmolar specimens are p57-positive and biparental diploid. Androgenetic/biparental mosaic/chimeric conceptions can have morphologic features that overlap with HMs but are genetically distinct. This study characterizes 11 androgenetic/biparental mosaic/chimeric conceptions identified in a series of 473 products of conception specimens subjected to p57 immunohistochemistry and short tandem repeat genotyping. Fluorescence in situ hybridization was performed on 10 to assess ploidy. All cases were characterized by hydropically enlarged, variably sized and shaped villi. In 5 cases, the villi lacked trophoblastic hyperplasia, whereas in 6 there was a focal to extensive villous component with trophoblastic hyperplasia and features of CHM. The villi lacking trophoblastic hyperplasia were characterized by discordant p57 expression within individual villi (p57-positive cytotrophoblast and p57-negative stromal cells), whereas the villous components having trophoblastic hyperplasia were uniformly p57-negative in both cell types. Short tandem repeat genotyping of at least 2 villous areas in each case demonstrated an excess of paternal alleles in all regions, with variable paternal:maternal allele ratios (usually >2:1); pure androgenetic diploidy was identified in those cases with a sufficiently sized villous component having trophoblastic hyperplasia and features of CHM. Fluorescence in situ hybridization demonstrated uniform diploidy in 7 cases, including 4 of 5 tested cases with trophoblastic hyperplasia and 3 of 5 cases without trophoblastic hyperplasia. Two cases without trophoblastic hyperplasia had uniformly diploid villous stromal cells but 1 had triploid and 1 had tetraploid cytotrophoblast; 1 case with trophoblastic hyperplasia had uniformly diploid villous stromal cells but a mixture of diploid, triploid, and tetraploid cytotrophoblast. In 3 cases with a CHM component, persistent gestational trophoblastic disease developed. These results indicate that androgenetic/biparental mosaic/chimeric conceptions are most often an admixture of androgenetic diploid (p57-negative) and biparental diploid (p57-positive) cell lines but some have localized hyperdiploid components. Recognition of their distinctive p57 expression patterns and genotyping results can prevent misclassification as typical CHMs, PHMs, or nonmolar specimens. The presence of androgenetic cell lines, particularly in those with a purely androgenetic CHM component, warrants follow-up because of some risk of persistent gestational trophoblastic disease.
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