The role of the plasmid-mediated fluoroquinolone resistance genes as resistance mechanisms in pediatric infections due to Enterobacterales.

Introduction: Fluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug-resistant (MDR) Enterobacterales (Ent) infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies. Methods: A case-control study of children (0-18 years) at three Chicago hospitals was performed. Cases had infections by FQ-susceptible, ß-lactamase-producing (bla) Ent harboring a non- or low-level expression of PMFQR genes (PMFQS Ent). Controls had FQR infections due to bla Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed rep-PCR, MLST, and E. coli phylogenetic grouping. Whole genome sequencing was additionally performed on PMFQS Ent positive isolates. Demographics, comorbidities, and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed. Results: Of 170 ß-lactamase-producing Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). Eighty-five (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent was 4.3 and 6.2 years, respectively (p = NS). Of 23 PMFQS Ent, 56% were Klebsiella spp., and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes detected in PMFQS Ent were bla SHV ESBL (44%) and oqxAB (57%), and the corresponding genes detected in PMFQR Ent were bla CTX-M-1-group ESBL (79%) and aac(6')-Ib-cr (83%). Whole genome sequencing of PMFQS Ent revealed the additional presence of mcr-9, a transferable polymyxin resistance gene, in 47% of isolates, along with multiple plasmids and mobile genetic elements propagating drug resistance. Multivariable regression analysis showed that children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates containing multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found. Conclusions: Paradoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, and additional silent, yet transferrable antibiotic resistance genes such as mcr-9, affecting therapeutic options and suggesting the need to address infection prevention strategies to control spread. Control of PMFQS Ent infections will require validating community and healthcare-based sources and risk factors associated with acquisition.

Anterior Cruciate Ligament Tears in the Adolescent Population: Injury Demographics and Risk of Reinjury Among High School Athletes.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries is increasing among the adolescent population with a peak occurring in the high school age range. PURPOSE: To characterize recent epidemiologic trends of ACL injuries, ACL reconstruction (ACLR), and retear rates in high school adolescents based on age, participating sport, and mechanism of injury. STUDY DESIGN: Retrospective case series. METHODS: A prospectively maintained institutional database was retrospectively reviewed for all patients 18 or younger who underwent primary ACLR between 2015 and 2020. Odds ratios were calculated for baseline patient characteristics and their association with risk of retear. Multivariate regression analysis was also performed to identify the relationship between retear and specific categorical variables. RESULTS: A total of 482 patients were included, with a mean follow-up time of 13.0 ± 11.8 months. Patients were an average age of 16.1 ± 1.3 years old (range: 13 to 18 y). Initial presentation of ACL injuries in high school athletes often occurred at 16 years old regardless of the sport played. Based on age, high school freshmen and seniors are found to have an increased risk of ACL retear. One hundred three patients (21.6%) completed at least 2 or more years of follow-up after ACLR. Of these patients, 38.8% received a bone-tendon-bone (BTB) autograft, 36.9% hamstring autograft, 14.6% quadriceps tendon autograft, and 3.9% received hamstring allograft or other graft (eg, tibialis anterior and BTB allograft), respectively. There were 25 ipsilateral ACL retears that occurred in the patient cohort (5.2%). Thirteen (52%) of retears were females. Football and soccer were the most common sports played by patients with a retear of the ipsilateral knee (31.8% and 27.3%, respectively). Patients who were 13 to 14 or 18 years old ( P = 0.009 and 0.035, respectively) or who received a tibialis anterior/BTB allograft ( P = 0.002) were found to have increased risk of ACL retear compared with other age groups. When evaluating by sex, female soccer players had a greater risk of retear compared with male soccer players ( P = 0.007). When adjusting for multiple variables, (including age, sex, body mass index, primary reconstruction graft choice, sport, and length of follow-up), the odds of ipsilateral retear in patients who received hamstring autograft ( P = 0.02), sustained a contralateral ACL tear ( P = 0 .04), or a contact injury ( P = 0.01) were increased. CONCLUSION: Initial presentation of ACL injuries in high school athletes often occurs at 16 years old regardless of the sport played. Based on age, high school freshmen and seniors are found to have an increased risk of ACL retear. However, the overall rate of ACL retear in high school athletes of all ages is low. Patients who underwent ACLR with hamstring tendon autograft had a greater risk of retear compared with other graft types. Female soccer players also had a greater risk of ACL retear. High school athletes must take caution when in the early high school years (underclassman) and more senior years (upperclassman), as susceptibility for ACL retears is elevated. LEVEL OF EVIDENCE: Level IV.

Effectiveness of the COVID-19 Community Vulnerability Index in explaining COVID-19 deaths.

Objectives: To explore the effectiveness of a COVID-19 specific social vulnerability index, we examined the relative importance of four COVID-19 specific themes and three general themes of the COVID-19 Community Vulnerability Index (CCVI) in explaining COVID-19 mortality rates in Cook County, Illinois. Methods: We counted COVID-19 death records from the Cook County Medical Examiner's Office, geocoded incident addresses by census tracts, and appended census tracts' CCVI scores. Negative binomial regression and Random Forest were used to examine the relative importance of CCVI themes in explaining COVID-19 mortality rates. Results: COVID-19 specific Themes 6 (High risk environments) and 4 (Epidemiological factors) were the most important in explaining COVID-19 mortality (incidence rate ratio (IRR) = 6.80 and 6.44, respectively), followed by a general Theme 2 (Minority status & language, IRR = 3.26). Conclusion: The addition of disaster-specific indicators may improve the accuracy of social vulnerability indices. However, variance for Theme 6 was entirely from the long-term care resident indicator, as the other two indicators were constant at the census tract level. Thus, CCVI should be further refined to improve its effectiveness in identifying vulnerable communities. Also, building a more robust local data infrastructure is critical to understanding the vulnerabilities of local places.

Left atrial echocardiographic parameters predict the onset of atrial fibrillation: the SMASH2 scoring system.

BACKGROUND: As AF-associated morbidity and mortality are increasing, there is an acute need for improved surveillance and prevention strategies to reduce the impact of AF and related strokes. Specific echocardiographic parameters that can best predict future onset of AF within 3 months are lacking. METHODS: Twenty patients with AF, as identified by presence of ICD-9 diagnosis code, were compared with a control group of twenty age- and sex-matched patients selected from the same clinic population but without a diagnosis of AF. Transthoracic echocardiograms (TTE) obtained within 90 days prior to first documented AF episode (study group) or obtained closest to first clinic visit (control) were selected for review. RESULTS: Baseline characteristics, including age, BMI, presence of hypertension, hyperlipidemia, diabetes, and heart failure were comparable. Increased left atrial (LA) size (end systolic major axis in 2-chamber view: AF 4.62±0.03 vs control 3.79±0.21, P =0.03), increased mitral inflow (E/A ratio: AF 1.35±0.15 vs control 1.06±0.07, P =0.04), and reduced LA global longitudinal strain (AF -2.69±0.26 vs control - 3.59±0.31, P =0.04) were most closely associated with AF compared with the control group. Multivariate logistic regression was used to develop predictive models for AF onset. A combination of imaging and traditional clinical risk factors was the best AF prediction model with AUC of 0.94, which greatly exceeds the current best predictors published. From these parameters, we developed the SMASH2 scoring system for 90- day AF risk estimation. CONCLUSIONS: Risk factors for AF and early features of atrial cardiomyopathy including male sex, hypertension, LA enlargement, reduced mitral inflow, and reduced LA strain are powerful predictors of AF onset within 90 days, and may be used to prognosticate future AF risk.

Racial, ethnic and socioeconomic disparities in SARS-CoV-2 infection amongst children.

BACKGROUND: COVID-19 disproportionately affects racial and ethnic minority populations, but comparatively few epidemiologic studies have been performed on children as compared to adults. OBJECTIVES: To characterise factors associated with SARS-CoV-2 infections amongst children from Chicago, Illinois, USA. METHODS: A test-negative case-control study of children tested for SARS-CoV-2 (0-18 years) at three medical centres of the Rush University System for Health between 12 March and 7 December 2020 was conducted. Of 8462 children, 1,302 tested positive by real-time PCR or rapid (NAAT) testing. Infection with SARS-CoV-2 was analysed as the outcome variable; effects of predictors were assessed by logistic regression analysis. A Paediatric Risk Score Index with a concordance index of 72% of accuracy was created to predict SARS-CoV-2 infection. RESULTS: The median age of cases was 13 years. On multivariable analysis, factors associated with SARS-CoV-2 infection were being Hispanic/Latinx (odds ratio [OR] 2.45, 95% CI 1.99, 3.03); Black/African-American (OR 1.31, 95% CI 1.03, 1.66); overweight/obese (OR 1.27, 95% CI 1.02, 1.58); older age, 10-14 years (OR 1.70, 95% CI 1.39, 2.08), 15-18 years (OR 2.06, 95% CI 1.71, 2.47); from households with income <$50,000 (OR 1.36, 95% CI 1.17, 1.60); or residing in predominantly minority neighbourhoods (OR 1.45, 95% CI 1.17, 1.80). Infections were higher during the second "fall" wave (5 October 2020 onward) compared with the first "spring" wave (OR 2.30, 95% CI 2.01, 2.63). Within Chicago, racial/ethnic minority neighbourhoods had striking positivity rates, as high as 39% in majority Hispanic/Latinx West Lawn neighbourhood. In suburban Chicago, highest positivity rates (20%-28%) were in zip codes within Hispanic/Latinx communities. CONCLUSIONS: Infection with SARS-CoV-2 is more likely amongst children of Hispanic/Latinx ethnicity, Black/African-American race, aged 10-18 years, who are overweight/obese, from lower income households, and from minority neighbourhoods. Future studies should focus on the prevention of COVID-19 infection in children of highest risk.

A quantitative gain-independent assessment of the left atrial appendage as a method of thromboembolic risk stratification.

BACKGROUND: Visual assessment of the left atrial appendage (LAA) by echocardiography for the presence of thrombus is inherently qualitative. However, whether quantitative assessments can provide increased value over qualitative assessment has not been thoroughly examined. METHODS: One hundred and thirty-eight patients (mean age 59 ± 13 years, 70% male) undergoing transesophageal echocardiography prior to pulmonary vein isolation or electrical cardioversion were retrospectively studied. LAA were examined by two expert readers and identified as thrombus, sludge, spontaneous echocardiograph contrast, or normal. LAA were then separately examined to calculate a gain-independent ratio between the average pixel density of the LAA cavity and that of the LAA wall (C/W ratio). RESULTS: C/W ratio was significantly related with qualitative LAA analysis (p < 0.0001) and with thromboembolic events (OR 1.60, 95% CI 1.095-2.347, p = 0.02). The C/W ratio (AUC 0.73, 95% CI 0.60-0.86) was a reliable predictor for future thromboembolic events when compared to expert reader LAA assessment (Expert Reader 1 AUC = 0.72, 95% CI 0.53-0.90; Expert Reader 2 AUC = 0.69). CONCLUSIONS: The C/W ratio may be a complementary method to adjudicate thromboembolic risk in patients with AF that is readily quantifiable at time of TEE.

Improvements in global longitudinal strain after transcatheter aortic valve replacement according to race.

OBJECTIVE: In the United States, racial minorities are underrepresented among patients receiving transcatheter aortic valve replacement (TAVR) and data regarding their outcomes is limited. Global longitudinal strain (GLS) is a measure left ventricular function and has independently predicted outcomes after TAVR. The aim of this study is to assess changes in GLS after TAVR according to race and factors predicting these changes. METHODS: Electronic medical records of patients undergoing TAVR at the University of Illinois, Chicago and Jesse Brown Veteran's Administration Medical Center (Chicago, Illinois) from January 2017-February 2020 were reviewed retrospectively. The most recent transthoracic echocardiogram (TTE) prior to TAVR and the TTE 1-month post-procedure were used to determine GLS. Patients were included if both a pre- and post-procedure study were present and TTE images were of sufficient quality to process strain imaging. RESULTS: A total of 103 patients (average age 76 ± 12 years, 80% male, 42% white) were included. At 1-month post-TAVR, GLS improved for all races: white (-2.7 ± 3.5%, P<0.001), African-American (-2.8 ± 3.3%, P<0.001), and Hispanic (-2.0 ± 2.1%, P<0.001). There were no differences in the degree of improvement among races (P=0.62). Baseline GLS was negatively correlated with changes in GLS overall (r=-0.44, P<0.001). Baseline aortic valve area (cm2) was positively correlated with changes in GLS (r=0.2, P=0.036). CONCLUSIONS: This study demonstrated that GLS improved after TAVR independent of race with similar degrees of change across races. Baseline GLS and aortic valve area predicted strain improvement after TAVR, which suggests that those with more impaired LV function may benefit most from the procedure.

Common genetic variation in circadian clock genes are associated with cardiovascular risk factors in an African American and Hispanic/Latino cohort.

Misalignment of the internal circadian time with external physical time due to environmental factors or due to genetic variantion in circadian clock genes has been associated with increased incidence of cardiovascular risk factors. Common genetic variation in circadian genes in the United States have been identified predominantly in European ancestry individuals. We therefore examined the association between circadian clock single nucleotide polymorphisms (SNPs) in Clock, Cry1, Cry2, Bmal1 and Per3 genes and cardiovascular risk factors in African Americans and Hispanic/Latinos. We analyzed 17 candidate circadian SNPs in 1,166 subjects who self-identified as African-American or Hispanic/Latino and were enrolled in the UIC Cohort of Patients, Family and Friends. We found significant differences in the minor allele frequencies between African American and Hispanic/Latino subjects. Our analyses also established ethnic-specific SNPs that are associated with cardiovascular risk factors. In Hispanic/Latinos, the rs6850524 in Clock was associated with increased risk for hypertension, meanwhile rs12649507, rs4864546, and rs4864548 reduced the risk, also rs8192440 (Cry1) reduced the risk for type 2 diabetes. In African Americans, the Clock rs1801260 and rs6850524 were negatively associated with the presence of obesity; Bmal1 rs11022775 reduced the risk for dyslipidemia; and the Cry2 rs2292912 increased the risk for dyslipidemia and diabetes. Genetic variations in candidate circadian-clock genes are associated with risk factors for cardiovascular disease in African-Americans and Hispanic/Latinos. Our findings may help to improve cardiovascular risk assessment as well as better understand how circadian misalignment impacts cardiovascular risk in diverse populations.

Common genetic variants associated with obesity in an African-American and Hispanic/Latino population.

INTRODUCTION: Over 35% of all adults in the world are currently obese and risk of obesity in racial or ethnic minority groups exist in the US, but the causes of these differences are not all known. As obesity is a leading cause of cardiovascular disease, an improved understanding of risk factors across racial and ethnic groups may improve outcomes. OBJECTIVE: The objective of this study was to determine if susceptibility to obesity is associated with genetic variation in candidate single nucleotide polymorphisms (SNPs) in African Americans and Hispanic/Latinos. MATERIALS AND METHODS: We examined data from 534 African Americans and 557 Hispanic/Latinos participants from the UIC Cohort of Patients, Family and Friends. Participants were genotyped for the top 26 obesity-associated SNPs within FTO, MC4R, TUB, APOA2, APOA5, ADIPOQ, ARL15, CDH13, KNG1, LEPR, leptin, and SCG3 genes. RESULTS: The mean (SD) age of participants was 49±13 years, 55% were female, and mean body mass index (BMI) was 31±7.5 kg/m2. After adjusting for age and sex, we found that rs8050136 in FTO (odds ratio [OR] 1.40, 95% confidence interval [CI] 1.1-1.8; P = 0.01) among African Americans and rs2272383 in TUB (OR 1.34, 95% CI 1.04-1.71; P = 0.02) among Hispanic/Latinos were associated with obesity. However, none of the SNPs in multivariable analysis of either AA or H/L cohorts were significant when adjusted for multiple correction. CONCLUSIONS: We show that candidate SNPs in the FTO and TUB genes are associated with obesity in African Americans and Hispanic/Latinos individuals respectively. While the underlying pathophysiological mechanisms by which common genetic variants cause obesity remain unclear, we have identified novel therapeutic targets across racial and ethnic groups.

Missed opportunities to prevent cardiovascular disease in women with prior preeclampsia.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in women in every major developed country and in most emerging nations. Complications of pregnancy, including preeclampsia, indicate a subsequent increase in cardiovascular risk. There may be a primary care provider knowledge gap regarding preeclampsia as a risk factor for CVD. The objective of our study is to determine how often internists at an academic institution inquire about a history of preeclampsia, as compared to a history of smoking, hypertension and diabetes, when assessing CVD risk factors at well-woman visits. Additional aims were (1) to educate internal medicine primary care providers on the significance of preeclampsia as a risk factor for CVD disease and (2) to assess the impact of education interventions on obstetric history documentation and screening for CVD in women with prior preeclampsia. METHODS: A retrospective chart review was performed to identify women ages 18-48 with at least one prior obstetric delivery. We evaluated the frequency of documentation of preeclampsia compared to traditional risk factors for CVD (smoking, diabetes, and chronic hypertension) by reviewing the well-woman visit notes, past medical history, obstetric history, and the problem list in the electronic medical record. For intervention, educational teaching sessions (presentation with Q&A session) and education slide presentations were given to internal medicine physicians at clinic sites. Changes in documentation were evaluated post-intervention. RESULTS: When assessment of relevant pregnancy history was obtained, 23.6% of women were asked about a history preeclampsia while 98.9% were asked about diabetes or smoking and 100% were asked about chronic hypertension (p < 0.001). Education interventions did not significantly change rates of screening documentation (p = 0.36). CONCLUSION: Our study adds to the growing body of literature that women with a history of preeclampsia might not be identified as having increased CVD risk in the outpatient primary care setting. Novel educational programming may be required to increase provider documentation of preeclampsia history in screening.

Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs.

Importance: The association between obesity, an established risk factor for atrial fibrillation (AF), and response to antiarrhythmic drugs (AADs) remains unclear. Objective: To test the hypothesis that obesity differentially mediates response to AADs in patients with symptomatic AF and in mice with diet-induced obesity (DIO) and pacing induced AF. Design, Setting, and Participants: An observational cohort study was conducted including 311 patients enrolled in a clinical-genetic registry. Mice fed a high-fat diet for 10 weeks were also evaluated. The study was conducted from January 1, 2018, to June 2, 2019. Main Outcomes and Measures: Symptomatic response was defined as continuation of the same AAD for at least 3 months. Nonresponse was defined as discontinuation of the AAD within 3 months of initiation because of poor symptomatic control of AF necessitating alternative rhythm control therapy. Outcome measures in DIO mice were pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride. Results: A total of 311 patients (mean [SD] age, 65 [12] years; 120 women [38.6%]) met the entry criteria and were treated with a class I or III AAD for symptomatic AF. Nonresponse to class I AADs in patients with obesity was less than in those without obesity (30% [obese] vs 6% [nonobese]; difference, 0.24; 95% CI, 0.11-0.37; P = .001). Both groups had similar symptomatic response to a potassium channel blocker AAD. On multivariate analysis, obesity, AAD class (class I vs III AAD [obese] odds ratio [OR], 4.54; 95% Wald CI, 1.84-11.20; P = .001), female vs male sex (OR, 2.31; 95% Wald CI, 1.07-4.99; P = .03), and hyperthyroidism (OR, 4.95; 95% Wald CI, 1.23-20.00; P = .02) were significant indicators of the probability of failure to respond to AADs. Pacing induced AF in 100% of DIO mice vs 30% (P < .001) in controls. Furthermore, DIO mice showed a greater reduction in AF burden when treated with sotalol compared with flecainide (85% vs 25%; P < .01). Conclusions and Relevance: Results suggest that obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers. These findings may have implications for the management of AF in patients with obesity.

Quantitative analysis of spectral Doppler clicks in assessment of aortic stenosis.

OBJECTIVES: This study was performed to evaluate an additional echocardiographic spectral Doppler marker, which would identify severe aortic stenosis (AS). BACKGROUND: Echocardiography is most commonly utilized to assess AS and has been validated against invasive measurements. However, the data obtained are not always in agreement, leaving a conundrum regarding the true severity of AS and can lead to other diagnostic procedures. This highlights the importance of improved noninvasive diagnostic techniques. METHODS: Forty-eight indeterminate cases of calcific AS that had been previously evaluated by both echocardiography and cardiac catheterization were included in the study, using cardiac catheterization as the gold standard for calculation of aortic valve area (AVA). The intensity of opening and closing of the aortic valve, represented by bright vertical deflections on the CW spectral waveform, was quantified using ImageJ software to generate pixel intensity histograms to create opening and closing click (OC and CC) ratios. These ratios were compared with echocardiographic variables and catheterization AVA. RESULTS: Thirty-five patients were found to have severe AS and 13 patients were found to have nonsevere AS, as assessed by cardiac catheterization. CC ratio was found to be a significant predictor of severe AS with an OR 0.024 (95% CI: 0.002-0.378, P = .0079). Adding CC to a model using standard echocardiographic parameters resulted in significant improvement in the C-statistic (0.693 to 0.835, P = .0134). CONCLUSIONS: An additional Doppler marker measuring the aortic valve CC ratio has been found to improve detection of severe AS.

The Clinical and Molecular Epidemiology of CTX-M-9 Group Producing Enterobacteriaceae Infections in Children.

INTRODUCTION: The pandemic of extended-spectrum beta-lactamase-(ESBL)-producing Enterobacteriaceae (Ent) is strongly linked to the dissemination of CTX-M-type-ESBL-Ent. We sought to define the epidemiology of infections in children due to an emerging resistance type, CTX-M-9-group-producing-Ent (CTX-M-9-grp-Ent). METHODS: A retrospective matched case-control analysis of children with CTX-M-9-grp-Ent infections who received medical care at three Chicago area hospitals was performed. Cases were defined as children possessing extended-spectrum cephalosporin-resistant (ESC-R) infections due to blaCTX-M-9. PCR and DNA analysis assessed beta-lactamase (bla) genes, multi-locus sequence types (MLST) and phylogenetic grouping of E. coli. Controls were children with ESC-susceptible (ESC-S)-Ent infections matched one case to three controls by age, source, and hospital. The clinical-epidemiologic predictors of CTX-M-9-grp-Ent infection were assessed. RESULTS: Of 356 ESC-R-Ent isolates from children (median age 4.1 years), the CTX-M-9-group was the solely detected bla gene in 44 (12.4%). The predominant species was E. coli (91%) of virulent phylogroups D (60%) and B2 (40%). MLST revealed multiple strain types. On multivariable analysis, CTX-M-9-grp-Ent occurred more often in E. coli than other Ent genera (OR 7.4, 95% CI 2.4, 27.2), children of non-Black-White-Hispanic race (OR 7.4, 95% CI 2.4, 28.2), and outpatients (OR 4.5, 95% CI 1.7, 12.3), which was a very unexpected finding for infections due to antibiotic-resistant bacteria. Residents of South Chicago had a 6.7 times higher odds of having CTX-M-9-grp-Ent infections than those in the reference region (West), while residence in Northwestern Chicago was associated with an 81% decreased odds of infection. Other demographic, comorbidity, invasive-device, and antibiotic use differences were not found. CONCLUSION: CTX-M-9-grp-Ent infection may be associated with patient residence and is occurring in children without traditional in-patient exposure risk factors. This suggests that among children, the community environment may be a key contributor in the spread of these resistant pathogens.

Community Origins and Regional Differences Highlight Risk of Plasmid-mediated Fluoroquinolone Resistant Enterobacteriaceae Infections in Children.

BACKGROUND: Fluoroquinolones are uncommonly prescribed in children, yet pediatric multidrug resistant (MDR) enterobacteriaceae (Ent) infections often reveal fluoroquinolone resistance (FQR). We sought to define the molecular epidemiology of FQR and MDR-Ent in children. METHODS: A case-control analysis of children with MDR-Ent infections at 3 Chicago hospitals was performed. Cases were children with third-generation cephalosporin-resistant and/or carbapenem-resistant Ent infections. Polymerase chain reaction and DNA analysis assessed bla and plasmid-mediated FQR (PMFQR) genes. Controls were children with third-generation cephalosporin, fluoroquinolone, and carbapenem-susceptible Ent infections matched by age, source and hospital. We assessed clinical-epidemiologic predictors of PMFQR Ent infection. RESULTS: Of 169 third-generation cephalosporin-resistant and/or carbapenem-resistant Ent isolates from children (median age, 4.8 years), 85 were FQR; 56 (66%) contained PMFQR genes. The predominant organism was Escherichia coli, and most common bla gene blaCTX-M-1 group. In FQR isolates, PMFQR gene mutations included aac6'1bcr, oqxA/B, qepA and qnrA/B/D/S in 83%, 15%, 13% and 11% of isolates, respectively. FQR E. coli was often associated with phylogroup B2, ST43/ST131. On multivariable analysis, PMFQR Ent infections occurred mostly in outpatients (odds ratio, 33.1) of non-black-white-Hispanic race (odds ratio, 6.5). Residents of Southwest Chicago were >5 times more likely to have PMFQR Ent infections than those in the reference region, while residence in Central Chicago was associated with a 97% decreased risk. Other demographic, comorbidity, invasive-device, antibiotic use or healthcare differences were not found. CONCLUSIONS: The strong association of infection with MDR organisms showing FQR with patient residence rather than with traditional risk factors suggests that the community environment is a major contributor to spread of these pathogens in children.

Genetic modulation of atrial fibrillation risk in a Hispanic/Latino cohort.

Atrial fibrillation (AF) is the most prevalent cardiac rhythm disorder worldwide but the underlying genetic and molecular mechanisms and the response to therapies is not fully understood. Despite a greater burden of AF risk factors in Hispanics/Latinos the prevalence of AF remains low. Over the last decade, genome-wide association studies have identified numerous AF susceptibility loci in mostly whites of European descent. The goal of this study was to determine if the top 9 single nucleotide polymorphisms (SNPs) associated with AF in patients of European descent also increase susceptibility to AF in Hispanics/Latinos. AF cases were prospectively enrolled in the University of Illinois at Chicago (UIC) AF Registry and control subjects were identified from the UIC Cohort of Patients, Family and Friends. AF cases and controls were genotyped for 9 AF risk SNPs at chromosome 1q21: rs13376333, rs6666258; chr1q24: rs3903239; chr4q25: rs2200733; rs10033464; chr10q22: rs10824026; chr14q23: rs1152591; chr16q22: rs2106261 and rs7193343. The study sample consisted of 713 Hispanic/Latino subjects including 103 AF cases and 610 controls. Among the 8 AF risk SNPs genotyped, only rs10033464 SNP at chromosome (chr) 4q25 (near PITX2) was significantly associated with development of AF after multiple risk factor adjustment and multiple testing (adj. odds ratio [OR] 2.27, 95% confidence interval [CI] 1.31-3.94; P = 3.3 x 10-3). Furthermore, the association remained significant when the analysis was restricted to Hispanics of Mexican descent (adj. OR 2.32, 95% CI 1.35-3.99; P = 0.002. We confirm for the first time the association between a chromosome 4q25 SNP and increased susceptibility to AF in Hispanics/Latinos. While the underlying molecular mechanisms by which the chr4q25 SNP modulates AF risk remains unclear, this study supports a genetic basis for non-familial AF in patients of Hispanic descent.

Association Between Family History and Early-Onset Atrial Fibrillation Across Racial and Ethnic Groups.

Importance: There is a genetic predisposition to early-onset atrial fibrillation (EOAF) in European American individuals. However, the role of family history in the pathogenesis of EOAF in racial and ethnic minorities remains unclear. Objective: To determine whether probands with EOAF across racial and ethnic groups have a higher rate of AF in first-degree family members than racially and ethnically matched control patients with non-early-onset AF (non-EOAF). Design, Setting, and Participants: In this cohort study, patients prospectively enrolled in a clinical and genetic biorepository were administered baseline questionnaires that included questions about family history of AF. Early-onset AF was defined as AF occurring in probands aged 60 years or younger in the absence of structural heart disease. All other forms were categorized as non-EOAF. Recruitment took place from July 2015 to December 2017. Analysis was performed in January 2018. Main Outcomes and Measures: Primary analysis of reported family history of AF in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram. Results: Of 664 patients enrolled (mean [SD] age, 62 [12] years; 407 [61%] male), 267 (40%) were European American; 258 (39%), African American; and 139 (21%), Hispanic/Latino. There was a family history of AF in 36 probands with EOAF (49%) compared with 128 patients with non-EOAF (22%) (difference, 27%; 95% CI, 14%-40%; P < .001). On multivariable analysis, the adjusted odds of a proband with EOAF who was of African descent (odds ratio [OR], 2.69; 95% CI, 1.06-6.91; P < .001) or Hispanic descent (OR, 9.25; 95% CI, 2.37-36.23; P = .002) having a first-degree relative with AF were greater than those of European descent (OR, 2.51; 95% CI, 1.29-4.87; P = .006). Overall, probands with EOAF were more likely to have a first-degree relative with AF compared with patients with non-EOAF (adjusted OR, 3.02; 95% CI, 1.82-4.95; P < .001) across the 3 racial and ethnic groups. Atrial fibrillation in a first-degree family member was confirmed in 32% of probands with EOAF vs 11% of those with non-EOAF (difference, 21%; 95% CI, 11%-33%; P < .001). Furthermore, African American (28% vs 5%; difference, 23%; 95% CI, 4%-43%; P = .001), European American (35% vs 20%; difference, 15%; 95% CI, 1%-30%; P = .03), and Hispanic/Latino (30% vs 5%; difference, 25%; 95% CI, 4%-54%; P = .02) probands with EOAF were more likely to have a first-degree relative with confirmed AF vs racially and ethnically matched control patients with non-EOAF. The positive and negative predictive values for a family history of confirmed AF were both 89%. Conclusions and Relevance: Probands of African or Hispanic/Latino descent with EOAF were more likely to have a first-degree relative with AF when compared with European American individuals. These findings support genetic predisposition to EOAF across all 3 races.