Betamethasone treatment-to-delivery interval, retreatment, and severe intraventricular hemorrhage in infants <28 weeks' gestation.

BACKGROUND: Antenatal corticosteroids decrease the incidence of severe intraventricular hemorrhage (grades 3, 4) in preterm infants. It is unclear whether their beneficial effects on intraventricular hemorrhage wane with time (as occurs in neonatal respiratory distress) and if repeat courses can restore this effect. Previous randomized controlled trials of betamethasone retreatment found no benefit on severe intraventricular hemorrhage rates. However, the trials may have included an insufficient number of infants at risk for intraventricular hemorrhage to be able to adequately address this question. Severe intraventricular hemorrhages occur almost exclusively in infants born at <28 weeks' gestation, whereas only 7% (0%-16%) of the retreatment trials' populations were <28 weeks' gestation. OBJECTIVE: This study aimed to determine if the risk for severe intraventricular hemorrhage in infants delivered at <28 weeks' gestation increases when the betamethasone treatment-to-delivery interval increases beyond 9 days and to determine if betamethasone retreatment before delivery decreases the rate of hemorrhage. STUDY DESIGN: This was an observational study that examined the incidence of intraventricular hemorrhage before (epoch 1) and after (epoch 2) a practice change that encouraged obstetricians to retreat pregnant women still at high risk for delivery before 28 weeks' gestation when >9 days elapsed from the first dose of betamethasone. Multivariable analyses with logistic regression using generalized estimating equation techniques were conducted to examine the rates of intraventricular hemorrhage among 410 infants <28 weeks' gestation who were either delivered between 1 to 9 days (n=290) after the first 2-dose betamethasone course or ≥10 days (and eligible for retreatment) after the first course (n=120). RESULTS: After adjusting for potential confounding variables, infants who were delivered ≥10 days after a single betamethasone course had an increased risk for either severe intraventricular hemorrhage alone or the combined outcome severe intraventricular hemorrhage or death before 4 days (odds ratio, 2.8; 95% confidence interval, 1.2-6.6) when compared with infants who were delivered between 1 and 9 days after betamethasone. Among the 120 infants who were delivered ≥10 days after the first dose of betamethasone, 64 (53%) received a second or retreatment course of antenatal betamethasone. The severe intraventricular hemorrhage rate in infants whose mothers received a second or retreatment course of betamethasone was similar to the rate among infants who delivered within 1 to 9 days and significantly lower than among those who delivered ≥10 days without retreatment (odds ratio, 0.10; 95% confidence interval, 0.02-0.65). Following the change in guidelines, the rate of retreatment in infants who were delivered ≥10 days after the first betamethasone course (and before 28 weeks) increased from epoch 1 to epoch 2 (25% to 87%; P<.001) and the rate of severe intraventricular hemorrhage decreased from 22% to 0% (P<.001). In contrast, the rate of severe intraventricular hemorrhage among infants who were delivered 1 to 9 days after the initial betamethasone dose (who were not eligible for retreatment) did not change between epochs 1 and 2 (12% and 11%, respectively). CONCLUSION: Although betamethasone's benefits on severe intraventricular hemorrhage appear to wane after the first dose, retreatment with a second course seems to restore its beneficial effects. Encouraging earlier retreatment of women at high risk for delivery before 28 weeks was associated with a lower rate of severe intraventricular hemorrhages among infants delivered at <28 weeks' gestation.

Patent ductus arteriosus and the risk of bronchopulmonary dysplasia-associated pulmonary hypertension.

BACKGROUND: The aim of the study was to determine whether prolonged exposure to a moderate/large patent ductus arteriosus left-to-right shunt (PDA) increases the risk of late (beyond 36 weeks) pulmonary hypertension (BPD-PH) and pulmonary vascular disease (BPD-PVD) during the neonatal hospitalization in preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD). METHODS: All infants requiring respiratory support ≥36 weeks had systematic echocardiographic evaluations for BPD-PH at planned intervals. Infants were classified as having either flow-associated BPD-PH (BPD-flow-PH) or BPD-PVD. RESULTS: 256 infants survived ≥36 weeks: 105 had NO BPD (were off respiratory support by 36 weeks); 151 had BPD. 22/151 had BPD-PH (12/22 had BPD-flow-PH from a PDA that persisted beyond 36 weeks; 10/22 had BPD-PVD). Moderate/large PDA shunts that persisted beyond 36 weeks were significantly associated with an increased incidence of BPD-PH due to BPD-flow-PH. We found no association between the duration of PDA exposure and the incidence of BPD-PVD. CONCLUSIONS: Moderate/large PDA shunts increase the risk of flow-associated BPD-PH when present beyond 36 weeks. Although term infants with PDA-congenital heart disease can develop pulmonary vascular remodeling and PVD after months of PDA exposure, we found no echocardiographic evidence in preterm infants that prolonged PDA exposure increases the incidence of BPD-PVD during the neonatal hospitalization. IMPACT: In our study, preterm infants (<28 weeks' gestation) with bronchopulmonary dysplasia (BPD) had a 15% incidence of pulmonary hypertension (PH) beyond 36 weeks' postmenstrual age as a comorbidity. Moderate/large patent ductus arteriosus (PDA) shunts increased the risk of flow-associated PH when present beyond 36 weeks. Although months of prolonged PDA exposure can cause pulmonary vascular remodeling and pulmonary vascular disease (PVD) in term infants with PDA-congenital heart disease, we found no echocardiographic evidence for an association between the duration of PDA exposure and the incidence of late PVD during the neonatal hospitalization in preterm infants with BPD.

Telemedicine in an adolescent and young adult medicine clinic: a mixed methods study.

BACKGROUND: Adolescents and young adults are a diverse patient population with unique healthcare needs including sensitive and confidential services. Many clinics serving this population began offering telemedicine during the Covid-19 pandemic. Little is known regarding patient and parent experiences accessing these services via telemedicine. METHODS: To assess for trends and disparities in telemedicine utilization in the first year of the pandemic, we used the electronic health record to obtain patient demographic data from an adolescent and young adult medicine clinic in a large urban academic institution. Characteristics of patients who had accessed telemedicine were compared to those who were only seen in person. Mean age was compared using t-test, while other demographic variables were compared using chi-squared test or Fisher's exact test. We performed qualitative semi-structured interviews with patients and parents of patients in order to characterize their experiences and preferences related to accessing adolescent medicine services via telemedicine compared to in-person care. RESULTS: Patients that identified as female, white race, Hispanic/Latinx ethnicity were more likely to have utilized telemedicine. Telemedicine use was also more prevalent among patients who were privately insured and who live farther from the clinic. Although interview participants acknowledged the convenience of telemedicine and its ability to improve access to care for people with geographic or transportation barriers, many expressed preferences for in-person visits. This was based on desire for face-to-face interactions with their providers, and perception of decreased patient and parent engagement in telemedicine visits compared to in-person visits. Participants also expressed concern that telemedicine does not afford as much confidentiality for patients. CONCLUSIONS: More work is needed to address patient and parent preferences for telemedicine as an adjunct modality to in-person adolescent and young adult medicine services. Optimizing quality and access to telemedicine for this patient population can improve overall healthcare for this patient population.

Hemorrhagic Stroke in Children and Adults With Sickle Cell Anemia: The Post-STOP Cohort.

BACKGROUND: Hemorrhagic stroke in young patients with sickle cell anemia remains poorly characterized. METHODS: The Post-STOP (Stroke Prevention Trial in Sickle Cell Anemia) retrospective study collected follow-up data on STOP and STOP II clinical trial cohorts. From January 2012 to May 2014, a team of analysts abstracted data from medical records of prior participants (all with sickle cell anemia). Two vascular neurologists reviewed data to confirm hemorrhagic strokes defined as spontaneous intracerebral, subarachnoid, or intraventricular hemorrhage. Incidence rates were calculated using survival analysis techniques Results: Follow-up data were collected from 2850 of 3835 STOP or STOP II participants. Patients (51% male) were a median of 19.1 (interquartile range, 16.6-22.6) years old at the time of last known status. The overall hemorrhagic stroke incidence rate was 63 per 100 000 person-years (95% CI, 45-87). Stratified by age, the incidence rate per 100 000 person-years was 50 (95% CI, 34-75) for children and 134 (95% CI, 74-243) for adults >18 years. Vascular abnormalities (moyamoya arteriopathy, aneurysm or cavernous malformation) were identified in 18 of 35 patients with hemorrhagic stroke. CONCLUSIONS: The incidence rate of hemorrhagic stroke in patients with sickle cell anemia increases with age. Structural vascular abnormalities such as moyamoya arteriopathy and aneurysms are common etiologies for hemorrhage and screening may be warranted.

Comparative 1-Year Outcomes of Invasive Staphylococcus aureus Infections Among Persons With and Without Drug Use: An Observational Cohort Study.

BACKGROUND: Persons who use drugs (PWUD) face substantial risk of Staphylococcus aureus infections. Limited data exist describing clinical and substance use characteristics of PWUD with invasive S. aureus infections or comparing treatment and mortality outcomes in PWUD vs non-PWUD. These are needed to inform optimal care for this marginalized population. METHODS: We identified adults hospitalized from 2013 to 2018 at 2 medical centers in San Francisco with S. aureus bacteremia or International Classification of Diseases-coded diagnoses of endocarditis, epidural abscess, or vertebral osteomyelitis with compatible culture. In addition to demographic and clinical characteristic comparison, we constructed multivariate Cox proportional hazards models for 1-year infection-related readmission and mortality, adjusted for age, race/ethnicity, housing, comorbidities, and methicillin-resistant S. aureus (MRSA). RESULTS: Of 963 hospitalizations for S. aureus infections in 946 patients, 372 of 963 (39%) occurred in PWUD. Among PWUD, heroin (198/372 [53%]) and methamphetamine use (185/372 [50%]) were common. Among 214 individuals using opioids, 98 of 214 (46%) did not receive methadone or buprenorphine. PWUD had lower antibiotic completion than non-PWUD (70% vs 87%; P < .001). While drug use was not associated with increased mortality, 1-year readmission for ongoing or recurrent infection was double in PWUD vs non-PWUD (28% vs 14%; adjusted hazard ratio [aHR], 2.0 [95% confidence interval {CI}: 1.3-2.9]). MRSA was independently associated with 1-year readmission for infection (aHR, 1.5 [95% CI: 1.1-2.2]). CONCLUSIONS: Compared to non-PWUD, PWUD with invasive S. aureus infections had lower rates of antibiotic completion and twice the risk of infection persistence/recurrence at 1 year. Among PWUD, both opioid and stimulant use were common. Models for combined treatment of substance use disorders and infections, particularly MRSA, are needed.

Interactions between PDA-associated polymorphisms and genetic ancestry alter ductus arteriosus gene expression.

BACKGROUND: DNA polymorphisms in PTGIS and TFAP2B have been identified as risk factors for patent ductus arteriosus (PDA) in a population composed of preterm infants with European genetic ancestry but not in more genetically diverse populations. GOAL: To determine if the effects of TFAP2B and PTGIS polymorphisms on ductus arteriosus (DA) gene expression differ based on genetic ancestry. METHODS: DA from 273 human second trimester fetuses were genotyped for TFAP2B and PTGIS polymorphisms and for polymorphisms distributing along genetic ancestry lines. RT-PCR was used to measure the RNA expression of 49 candidate genes involved with DA closure. RESULTS: Seventeen percent of the DA analyzed were of European ancestry. In multivariable regression analyses we found consistent associations between four PDA-related TFAP2B polymorphisms (rs2817399(A), rs987237(G), rs760900(C), and rs2817416(C)) and expression of the following genes: EPAS1, CACNB2, ECE1, KCNA2, ATP2A3, EDNRA, EDNRB, BMP9, and BMP10, and between the PTGIS haplotype rs493694(G)/rs693649(A) and PTGIS and NOS3. These changes only occurred in DA with European ancestry. No consistent positive or negative associations were found among DA samples unless an interaction between the polymorphisms and genetic ancestry was taken into account. CONCLUSION: PTGIS and TFAP2B polymorphisms were associated with consistent changes in DA gene expression when present in fetuses with European ancestry. IMPACT: DNA polymorphisms in PTGIS and TFAP2B have been identified as risk factors for patent ductus arteriosus (PDA) in a population composed primarily of preterm infants with European genetic ancestry but not in more genetically diverse populations. The same PTGIS and TFAP2B polymorphisms are associated with changes in ductus gene expression when present in ductus from fetuses with European genetic ancestry. No consistent associations with gene expression can be found unless an interaction between the polymorphisms and genetic ancestry is taken into account.

Patent ductus arteriosus, tracheal ventilation, and the risk of bronchopulmonary dysplasia.

BACKGROUND: An increased risk for bronchopulmonary dysplasia (BPD) exists when moderate-to-large patent ductus arteriosus shunts (hsPDA) persist beyond 14 days. GOAL: To examine the interaction between prolonged exposures to tracheal ventilation (≥10 days) and hsPDA on the incidence of BPD in infants <28 weeks gestation. STUDY DESIGN: Predefined definitions of prolonged ventilation (≥10 days), hsPDA (≥14 days), and BPD (room air challenge test at 36 weeks) were used to analyze deidentified data from the multicenter TRIOCAPI RCT in a secondary analysis of the trial. RESULTS: Among 307 infants who survived >14 days, 41 died before 36 weeks. Among survivors, 93/266 had BPD. The association between BPD and hsPDA depended on the length of intubation. In multivariable analyses, prolonged hsPDA shunts were associated with increased BPD (odds ratio (OR) (95% confidence interval (CI)) = 3.00 (1.58-5.71)) when infants required intubation for ≥10 days. In contrast, there was no significant association between hsPDA exposure and BPD when infants were intubated <10 days (OR (95% CI) = 1.49 (0.98-2.26)). A similar relationship between prolonged hsPDA and length of intubation was found for BPD/death (n = 307): infants intubated ≥10 days: OR (95% CI) = 2.41 (1.47-3.95)); infants intubated <10 days: OR (95% CI) = 1.37 (0.86-2.19)). CONCLUSIONS: Moderate-to-large PDAs were associated with increased risks of BPD and BPD/death-but only when infants required intubation ≥10 days. IMPACT: Infants with a moderate-to-large hsPDA that persist beyond 14 days are only at risk for developing BPD if they also receive prolonged tracheal ventilation for ≥10 days. Infants who receive less ventilatory support (intubation for <10 days) have the same incidence of BPD whether the ductus closes shortly after birth or whether it persists as a moderate-to-large shunt for several weeks. Early PDA closure may be unnecessary in infants who require short durations of intubation since the PDA does not seem to alter the incidence of BPD in infants who require intubation for <10 days.

Imaging Predictors of Neurologic Outcome After Pediatric Arterial Ischemic Stroke.

BACKGROUND AND PURPOSE: To assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients. METHODS: We used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome. RESULTS: Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome. CONCLUSIONS: In the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.

Accuracy of Disclosed Financial Relationships between Radiologists and Industry at the 2018 RSNA Annual Meeting.

Online supplemental material is available for this article. See also the editorial by Grant in this issue.

Association of comorbid depression with inpatient outcomes in critical limb ischemia.

There is a growing body of evidence that peripheral artery disease (PAD) may be impacted by depression. The objective of this study is to determine whether outcomes, primarily major amputation, differ between patients with depression and those without who presented to hospitals with critical limb ischemia (CLI), the end-stage of PAD. A retrospective cohort of patients hospitalized for CLI during 2012 and 2013 was identified from the National Inpatient Sample (NIS) using ICD-9 codes. The primary outcome was major amputation and secondary outcomes were length of stay and other complications. The sample included 116,008 patients hospitalized for CLI, of whom 10,512 (9.1%) had comorbid depression. Patients with depression were younger (64 ± 14 vs 67 ± 14 years, p < 0.001) and more likely to be female (55% vs 41%, p < 0.001), white (73% vs 66%, p < 0.001), and tobacco users (46% vs 41%, p < 0.001). They were also more likely to have prior amputations (9.8% vs 7.9%, p < 0.001). During the hospitalization, the rate of major amputation was higher in patients with comorbid depression (11.5% vs 9.1%, p < 0.001). In multivariable analysis, excluding patients who died prior to/without receiving an amputation (n = 2621), comorbid depression was associated with a 39% increased odds of major amputation (adjusted OR 1.39, 95% CI 1.30, 1.49; p < 0.001). Across the entire sample, comorbid depression was also independently associated with a slightly longer length of stay (ß = 0.199, 95% CI 0.155, 0.244; p < 0.001). These results provide further evidence that depression is a variable of interest in PAD and surgical quality databases should include mental health variables to enable further study.

Relationship between Duration of Infant Exposure to a Moderate-to-Large Patent Ductus Arteriosus Shunt and the Risk of Developing Bronchopulmonary Dysplasia or Death Before 36 Weeks.

OBJECTIVE: This study was aimed to examine the relationship between duration of infant exposure to a moderate-to-large patent ductus arteriosus (PDA) shunt and the risk of developing bronchopulmonary dysplasia (BPD) or death before 36 weeks (BPD/death). STUDY DESIGN: Infants <28 weeks' gestation who survived ≥7 days (n = 423) had echocardiograms performed on day 7 and at planned intervals. RESULTS: In multivariable regression models, BPD/death did not appear to be increased until infants had been exposed to a moderate-to-large PDA for at least 7-13 days: OR (95%CI) (referent = closed or small PDA): moderate-to-large PDA exposure for <7 days: 0.38 (range, 0.10-1.46); for 7 to 13 days = 2.12 (range, 1.04-4.32); for ≥14 days = 3.86 (range, 2.15-6.96). Once the threshold of 7 to 13 days had been reached, additional exposure (≥14 days) did not significantly add to the increased incidence of BPD/death: (referent exposure = 7-13 days) exposure for 14 to 27 days = 1.34 (range, 0.52-3.45); for 28 to 48 days = 2.34 (range, 0.88-6.19); for ≥49 days = 1.80 (range. 0.59-5.47). A similar relationship was found for the outcome of BPD-alone. CONCLUSION: Infants < 28 weeks' gestation required at least 7 to 13 days of exposure to a moderate-to-large PDA before a significant increase in the incidence of BPD/death was apparent. Once this threshold was reached additional exposure to a moderate-to-large PDA did not significantly add to the increased incidence of BPD/death.

Serum resistin is associated with impaired endothelial function and a higher rate of adverse cardiac events in patients with peripheral artery disease.

OBJECTIVE: Resistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD. METHODS: There were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause. RESULTS: Patients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P = .002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, -2.26 [95% confidence interval (CI), -4.51 to -0.01; P = .05]; IV, -2.53 [95% CI, -4.87 to -0.20; P = .03]). During a median follow-up period of 36 months (interquartile range, 29-45 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04). CONCLUSIONS: In patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population.

Radial Artery Tonometry is Associated With Major Adverse Cardiac Events in Patients With Peripheral Artery Disease.

BACKGROUND: Peripheral artery disease (PAD) is associated with increased arterial stiffness, as measured by an increasing radial artery augmentation index (AIX). However, it has not yet been clearly demonstrated whether AIX is associated with adverse cardiovascular outcomes in a PAD population. MATERIALS AND METHODS: Seventy-two patients with PAD were recruited between 2011 and 2016. Radial artery applanation tonometry was performed at a baseline visit, and the central AIX, normalized to 75 beats/min, and the peripheral AIX were calculated using pulse wave analysis. Incident major adverse cardiac events (MACEs) were identified by subsequent chart review. RESULTS: Study subjects had comorbidities commonly associated with PAD including a high prevalence of hypertension (93%), hyperlipidemia (85%), coronary artery disease (39%), and diabetes mellitus (39%). During a median follow-up period of 34 mo (interquartile range 29-38), 14 patients experienced a MACE. In a univariate Cox proportional hazards model, a 10-unit increase in the peripheral AIX was significantly associated with a 54% increased rate of MACE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.06-2.22, P = 0.02), but central AIX, normalized to 75 beats/min, was not (HR 1.33, 95% CI 0.71-2.47, P = 0.37). In a multivariable model adjusted for coronary artery disease, age, and Rutherford category the peripheral AIX remained significantly associated with MACE (HR 1.70, 95% CI 1.10-2.62, P = 0.02). CONCLUSIONS: Increased arterial stiffness, as measured by the peripheral AIX, was independently associated with an increased rate of MACE in patients with PAD. The use of radial artery tonometry should be contemplated as a tool for risk stratification in patients with PAD.

Fish Oil Increases Specialized Pro-resolving Lipid Mediators in PAD (The OMEGA-PAD II Trial).

BACKGROUND: N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD). MATERIALS AND METHODS: The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD. RESULTS: Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 ± 1.2%, P < 0.001; placebo: -0.4 ± 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and mono-hydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A5 (fish oil: 0.57 ± 0.70 pg/mL, P = 0.05; placebo: 0.01 ± 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 ± 171 pg/mL, P = 0.04; placebo: 32 ± 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity C-reactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group. CONCLUSIONS: Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD.

Leptinemia is Associated With Peripheral Artery Disease.

BACKGROUND: Leptin, adiponectin, and resistin are in a class of hormones called adipokines that are produced by adipocytes and have been implicated in the causal pathway of atherosclerosis. We examined the association between adipokine levels and peripheral artery disease (PAD), hypothesizing that after adjusting for fat mass, leptin and resistin would be higher, whereas adiponectin would be lower, in patients with PAD. METHODS: A cross-sectional sample of 179 predominately male (97%) vascular surgery outpatients was recruited from the San Francisco Veterans Affairs Medical Center (SFVAMC). PAD was defined as either an ankle-brachial index < 0.9 plus symptoms of claudication or prior revascularization for symptomatic PAD (n = 141). Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic disease (n = 38). Adipokines were assayed using commercially available ELISA kits and values were log-transformed. Fat mass was measured using bioelectrical impedance. RESULTS: In an analysis adjusting for body mass index (BMI) and atherosclerotic risk factors, higher serum leptin was associated with PAD (OR 2.54, 95% CI 1.07-6.01, P = 0.03), whereas high molecular weight adiponectin was inversely associated, though not significantly (OR 0.60, 95% CI 0.33-1.08, P = 0.09). Resistin was not associated with PAD. Sensitivity analyses using fat mass/height2 rather than BMI yielded similar results. CONCLUSIONS: These results indicate that after adjusting for BMI or fat mass, serum leptin levels are positively and independently associated with PAD, whereas high molecular weight adiponectin might be inversely associated. Using a more representative, nonveteran sample, further investigations should focus on the potential role of adipokines in the pathophysiology of PAD as well as determine whether leptin levels have clinical utility in predicting PAD outcomes.

Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History.

Background and Purpose- Focal cerebral arteriopathy (FCA)-a common cause of arterial ischemic stroke in previously healthy children-often progresses over days to weeks, increasing the risk of recurrent stroke. We developed a novel severity scoring system designed to quantify FCA progression and correlate with clinical outcomes. Methods- The VIPS study (Vascular Effects of Infection in Pediatric Stroke) prospectively enrolled 355 children with arterial ischemic stroke (2010-2014), including 41 with centrally confirmed FCA. Two neuroradiologists independently reviewed FCA cerebrovascular imaging, assigning a graded severity score of zero (no involvement) to 4 (occlusion) to individual arterial segments. The FCA severity score (FCASS) was the unweighted sum. In an iterative process, we modeled scores derived from different combinations of arterial segments to identify the model that optimized correlation with clinical outcome, simplicity, and reliability. Results- The optimal FCASS summed scores from 5 arterial segments: supraclinoid internal carotid artery, A1, A2, M1, and M2. The median (interquartile range) baseline FCASS was 4 (2-6). Of 33 children with follow-up imaging, the maximum FCASS (at any time point) was 7 (5-9). Twenty-four (73%) had FCA progression on follow-up with their maximum FCASS at a median of 8 (5-35.5) days poststroke; their median FCASS increase was 4 (2.5-6). FCASS did not correlate with recurrent arterial ischemic stroke. Maximum (but not baseline) FCASS correlated with 1-year pediatric stroke outcome measures ( P=0.037). Conclusions- Our novel scoring system for FCA severity correlates with neurological outcomes in the VIPS cohort and provides a tool for FCA treatment trials under development.

Characterizing the relationship between flow-mediated vasodilation and radial artery tonometry in peripheral artery disease.

BACKGROUND: Arterial stiffness, measured by the augmentation index (AIX) from radial artery tonometry, and endothelial dysfunction, measured by brachial-artery flow-mediated vasodilation (FMD), have each been associated with increased risk of cardiovascular events. However, their interrelationship in peripheral artery disease (PAD) patients is poorly understood. MATERIALS AND METHODS: In a cross-sectional analysis of 123 vascular surgery outpatients, the association between FMD and AIX was examined in controls with atherosclerotic risk factors (n = 32) and patients with PAD (n = 91). PAD was defined as claudication symptoms with an ankle-brachial index of <0.9 or a history of revascularization for symptomatic PAD. Controls had an ankle-brachial index ≥0.9 and no history of atherosclerotic vascular disease. RESULTS: Compared to controls, patients with PAD had lower FMD (6.3 ± 3.8 versus 8.4 ± 3.7, P = 0.008), while central AIX normalized to 75 beats per minute (25.5 ± 9.0 versus 19.3 ± 8.6, P = 0.001) and peripheral AIX (91.3 ± 14.5 versus 81.3 ± 11.4, P = 0.001) were higher. FMD was not significantly correlated with either central or peripheral AIX (central AIX: P = 0.58; peripheral AIX: P = 0.89) across the entire cohort, or in either the patients with PAD (central AIX: P = 0.48; peripheral AIX: P = 0.23) or controls (central AIX: P = 0.43; peripheral AIX: P = 0.92). In a multivariate model including FMD, higher AIX remained independently associated with PAD. CONCLUSIONS: In an analysis of vascular surgery outpatients, no correlation between FMD and AIX was detected. Larger prospective studies are needed to determine whether the inclusion of both parameters improves predictive models for the early identification and potential risk stratification of PAD patients.

Home-Based Care and Perceived Quality of Life Among People Living with HIV in Ho Chi Minh City, Viet Nam.

We conducted a cross-sectional study to examine the perceptions of quality of life among people living with HIV who received home-based care services administered through outpatient clinics in Ho Chi Minh City, Viet Nam. Data were collected from a sample of 180 consecutively selected participants (86 cases, 94 controls) at four outpatient clinics, all of whom were on antiretroviral therapy. Quality of life was evaluated using the WHOQOL-BREF instrument. In adjusted analysis, those who received home-based care services had a quality of life score 4.08 points higher (on a scale of 100) than those who did not receive home-based care services (CI 95%, 2.32-5.85; p < 0.001). The findings suggest that home-based care is associated with higher self-perceptions of quality of life among people living with HIV.

Symptoms of Depression in People Living with HIV in Ho Chi Minh City, Vietnam: Prevalence and Associated Factors.

This cross-sectional study investigated the prevalence and correlates of symptoms of depression among 400 people living with HIV/AIDS (PLHIV) from two HIV clinics in Ho Chi Minh City, Vietnam. Based on the Center for Epidemiologic Studies-Depression scale, 36.5% of participants were classified as likely to be clinically depressed. Factors independently associated with symptoms of depression included self-report of poor or fair health (aOR 2.16, 95% CI 1.33-3.51), having a low body mass index (aOR 1.85, 95% CI 1.13-3.04), reporting recent problems with family (aOR 1.97, 95% CI 1.21-3.19), feeling shame about being HIV-infected (aOR 1.90, 95% CI 1.20-3.00), and reporting conflict with a partner (aOR 2.21, 95% CI 1.14-4.26). Participants who lived with family (aOR 0.48, 95% CI 0.25-0.90) or who received emotional support from their families or supportive HIV networks (aOR 0.45, 95% CI 0.25-0.80) were less likely to experience symptoms of depression. Screening for and treatment of depression among Vietnamese PLHIV are needed.