Mandibular Measurements at the 20-Week Anatomy Ultrasound as a Prenatal Diagnostic Predictor of Pierre Robin Sequence.

BACKGROUND: Pierre Robin Sequence (PRS) is characterized by micrognathia, glossoptosis, and upper airway obstruction. Early recognition and appropriate perinatal management is crucial for optimizing outcomes. This study aimed to evaluate 20-week fetal ultrasounds to determine if specific mandibular measurements could predict PRS diagnosis and disease severity. METHODS: A retrospective case-control study of 48 patients with PRS and gender-matched controls was performed. Medical records were reviewed for respiratory and surgical interventions. Three parameters to assess micrognathia were measured on mid-sagittal profile ultrasound images: frontal nasal-mental angle (FNMA), facial-maxillary angle (FMA), and alveolar overjet. Student's t-test and univariate logistic regression was performed. P ≤ 0.05 was considered statistically significant. RESULTS: Patients with PRS demonstrated a significantly smaller mean FNMA compared to the control group, 129.3 ± 8.6° and 137.4 ± 3.2°, respectively (p < 0.0001), as well as significantly smaller mean FMA, 63.2 ± 9.2° and 74.8 ± 6.1°, respectively (p < 0.0001). The PRS group also demonstrated significantly larger mean alveolar overjet compared to the control group, 3.9 ± 1.4 mm and 2.1 ± 0.9 mm, respectively (p < 0.0001). The odds of respiratory intervention increased among cases when FMA was <68°. Additionally, there was a significant difference in median overjet between patients with PRS who did and did not require respiratory intervention. CONCLUSIONS: Mandibular features on the 20-week ultrasound can be measured to predict diagnosis and severity of PRS. This is an important first step to prepare for potential respiratory intervention at delivery to minimize perinatal hypoxia. Alveolar overjet, previously not described in prenatal ultrasound literature, is measurable and has utility in prenatal screening for PRS, as do FMA and FNMA.

Enhanced Recovery Protocols Reduce Mortality Across Eight Surgical Specialties at Academic and University-affiliated Community Hospitals.

OBJECTIVE: To determine if implementation of a simplified ERP across multiple surgical specialties in different hospitals is associated with improved short and long-term mortality. Secondary aims were to examine ERP effect on length of stay, 30-day readmission, discharge disposition, and complications. SUMMARY BACKGROUND DATA: Enhanced recovery after surgery and various derivative ERPs have been successfully implemented. These protocols typically include elaborate sets of multimodal and multidisciplinary approaches, which can make implementation challenging or are variable across different specialties. Few studies have shown if a simplified version of ERP implemented across multiple surgical specialties can improve clinical outcomes. METHODS: A simplified ERP with 7 key domains (minimally invasive surgical approach when feasible, pre-/intra-operative multimodal analgesia, postoperative multimodal analgesia, postoperative nausea and vomiting prophylaxis, early diet advancement, early ambulation, and early removal of urinary catheter) was implemented in 5 academic and community hospitals within a single health system. Patients who underwent nonemergent, major orthopedic or abdominal surgery including hip/knee replacement, hepatobiliary, colorectal, gynecology oncology, bariatric, general, and urological surgery were included. Propensity-matched, retrospective case-control analysis was performed on all eligible surgical patients between 2014 and 2017 after ERP implementation or in the 12 months preceding ERP implementation (control population). RESULTS: A total of 9492 patients (5185 ERP and 4307 controls) underwent ERP eligible surgery during the study period. Three thousand three hundred sixty-seven ERP patients were matched by surgical specialty and hospital site to control non-ERP patients. Short and long-term mortality was improved in ERP patients: 30 day: ERP 0.2% versus control 0.6% ( P = 0.002); 1-year: ERP 3.9% versus control 5.1% ( P < 0.0001); 2-year: ERP 6.2% versus control 9.0% ( P < 0.0001). Length of stay was significantly lower in ERP patients (ERP: 3.9 ± 3.8 days; control: 4.8 ± 5.0 days, P < 0.0001). ERP patients were also less likely to be discharged to a facility (ERP: 11.3%; control: 14.8%, P < 0.0001). There was no significant difference for 30-day readmission. All complications except venous thromboembolism were significantly reduced in the ERP population (P < 0.02). CONCLUSIONS: A simplified ERP can uniformly be implemented across multiple surgical specialties and hospital types. ERPs improve short and long-term mortality, clinical outcomes, length of stay, and discharge disposition to home.

Longitudinal Assessment of Cardiac Function Following Multisystem Inflammatory Syndrome in Children Associated with COVID-19.

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 is commonly associated with cardiac involvement. Studies found myocardial dysfunction, as measured by decreased ejection fraction and abnormal strain, to be common early in illness. However, there is limited data on longitudinal cardiac outcomes. We aim to describe the evolution of cardiac findings in pediatric MIS-C from acute illness through at least 2-month follow-up. A retrospective single-center review of 36 patients admitted with MIS-C from April 2020 through September 2021 was performed. Echocardiographic data including cardiac function and global longitudinal strain (GLS) were analyzed at initial presentation, discharge, 2-4-week follow-up, and at least 2-month follow-up. Patients with mild and severe disease, normal and abnormal left ventricular ejection fraction (LVEF), and normal and abnormal GLS at presentation were compared. On presentation, 42% of patients with MIS-C had decreased LVEF < 55%. In patients in whom GLS was obtained (N = 18), 44% were abnormal (GLS < |- 18|%). Of patients with normal LVEF, 22% had abnormal GLS. There were no significant differences in troponin or brain natriuretic peptide between those with normal and abnormal LVEF. In most MIS-C patients with initial LVEF < 55% (90%), LVEF normalized upon discharge. At 2-month follow-up, all patients had normal LVEF with 21% having persistently abnormal GLS. Myocardial systolic dysfunction and abnormal deformation were common findings in MIS-C at presentation. While EF often normalized by 2 months, persistently abnormal GLS was more common, suggesting ongoing subclinical dysfunction. Our study offers an optimistic outlook for recovery in patients with MIS-C and carditis, however ongoing investigation for longitudinal effects is warranted.

Omitting the Early Postoperative Follow-up in Uncomplicated Operative Supracondylar Humerus Fractures in Children Does Not Negatively Affect Outcomes.

BACKGROUND: Supracondylar humerus (SCH) fractures are the most common surgically treated elbow injuries in children. There have been debates regarding if an early postoperative follow-up before pin removal is necessary to decrease the complications related to surgical fixation. To date, studies examining this topic have included smaller sample sizes, limiting the generalizability of their findings. METHODS: A retrospective chart review of outcomes after operative management of Gartland type II and III SCH fractures at a single level 1 pediatric trauma center between 2005 and 2015 was performed. Patient demographics, fracture characteristics, pin number and configuration, timing of initial follow-up, change in treatment plan after initial follow-up, time to pin removal, initial and final fracture radiographic parameters, and complications were observed via chart review. RESULTS: A total of 1518 SCH fractures underwent operative fixation: 755 Gartland type II and 765 type III. Of the 1518 SCH fractures identified, 1370 met inclusion criteria and were included for analysis. Of these, 1196 patients returned for initial follow-up within 1 to 2 weeks of surgery, and 174 patients had their initial follow-up 3 to 4 weeks postoperatively. There were 8 incidences where initial early follow-up resulted in a change of management; however, change in management was limited to cast alteration in 7 of these cases. CONCLUSIONS: Closed reduction and percutaneous pin fixation of otherwise uncomplicated closed SCH fractures have good outcomes and a very low complication rate at a level 1 pediatric trauma center. Early postoperative follow-up before the pin removal visit provides minimal utility in decreasing complications and may be safely omitted as long as the initial fracture fixation is deemed to be stable. LEVEL OF EVIDENCE: Level III.

Targets for Intervention? Preoperative Predictors of Postoperative Ileus After Colorectal Surgery in an Enhanced Recovery Protocol.

BACKGROUND: Postoperative ileus occurs in up to 30% of colorectal surgery patients and is associated with increased length of stay, costs, and morbidity. While Enhanced Recovery Protocols seek to accelerate postoperative recovery, data on modifiable preoperative factors associated with postoperative ileus in this setting are limited. We aimed to identify preoperative predictors of postoperative ileus following colorectal surgery in Enhanced Recovery Protocols, to determine new intervention targets. METHODS: We performed a retrospective single-center cohort study of patients ≥ 18 years old who underwent colorectal surgery via Enhanced Recovery Protocols (7/2015-7/2017). Postoperative ileus was defined as nasogastric tube insertion postoperatively or nil-per-os by postoperative day 4. Preoperative risk factors including comorbidities and medication use were identified using multivariable stepwise logistic regression. RESULTS: Of 530 patients, 14.9% developed postoperative ileus. On univariate analysis of perioperative and postoperative factors, postoperative ileus patients had increased psychiatric illness, antidepressant and antipsychotic use, American Society of Anesthesiologists classification, ileostomy creation, postoperative opioid use, complications, surgery duration, and length of stay (p < 0.05). Multivariable logistic regression model for preoperative factors identified psychiatric illness, preoperative antipsychotic use, and American Society of Anesthesiologists classification ≥ 3 as significant predictors of postoperative ileus (p < 0.05). DISCUSSION: Postoperative ileus remains a common complication following colorectal surgery under Enhanced Recovery Protocols. Patients with pre-existing psychiatric comorbidities and preoperative antipsychotic use may be a previously overlooked cohort at increased risk for postoperative ileus. Additional research and preoperative interventions within Enhanced Recovery Protocols to reduce postoperative ileus for this higher-risk population are needed.

Epiphyseal Translation as a Predictor of Avascular Necrosis in Unstable Slipped Capital Femoral Epiphysis.

BACKGROUND: Physeal instability has been shown to be associated with a higher risk of avascular necrosis (AVN) in patients with slipped capital femoral epiphysis (SCFE). The purpose of this study was to identify additional preoperative factors associated with AVN in patients with unstable SCFE. METHODS: Basic demographic information, chronicity of symptoms, and estimated duration of nonambulatory status were noted. Preoperative radiographs were used to measure the Southwick slip angle, slip severity by Wilson criteria, and epiphyseal translation. Translation was measured by 3 distinct radiographic parameters in the position demonstrating maximal displacement. Postoperative radiographs at the time of most recent follow-up were assessed for the presence of AVN. Translation measurements were tested for inter-rater reliability. Patients who developed AVN were compared with those that did not by Fisher exact test and Wilcoxon tests. Logistic regression assessed the effect of translation on the odds of developing AVN. Receiver operating characteristic curve was plotted to assess any threshold effect. RESULTS: Fifty-one patients (55 hips) out of 310 patients (16%) treated for SCFE were considered unstable. Seventeen hips' unstable SCFE (31%) showed radiographic evidence of AVN. Slip severity by Wilson grade (P=0.009) and epiphyseal translation by all measurements (P< 0.05) were statistically significantly greater among patients who developed AVN. Superior translation had the best inter-rater reliability (intraclass correlation coefficient=0.84). Average superior translation in hips that developed AVN was 17.2 mm compared with 12.9 mm in those that did not (P<0.02). Although the receiver operating characteristic curve did not demonstrate a threshold effect for AVN, it did effectively rule out AVN in cases with <1 cm of superior translation. Age, sex, laterality, chronicity of prodromal symptoms or inability to bear weight, Southwick slip angle, and method of treatment did not vary with the occurrence of AVN. CONCLUSIONS: Epiphyseal translation, either by Wilson Grade or measured directly, is associated with AVN in patients with an unstable SCFE. LEVEL OF EVIDENCE: Level II-development of diagnostic criteria.

Intermediate-term annualized curve progression of adolescent idiopathic scoliosis curves measuring 40° or greater.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: The objective of this study was to examine intermediate-term progression for a large series of patients with adolescent idiopathic scoliosis (AIS) with curves 40° or greater. BACKGROUND: Curve progression in AIS has been well documented for smaller curves in adolescence up to skeletal maturity; however, the data on curve progression past 40° or into adulthood are limited. With many surgeons recommending surgical correction when patients reach this threshold, it is important to understand the radiographic progression of curves into adulthood. METHODS: A database of all patients seen by a single surgeon from 1984 through 2018 with AIS curves progressing to at least 40° entered prospectively was utilized for this study. This included a total of 738 patients. Curve progression was analyzed overall and stratified by length of follow-up, curve location, and Risser stage at the time of presentation among other variables. Curve magnitude and Risser stage designations in this study were validated by performing a separate inter- and intrarater agreement study using four independent reviewers reading 50 patients' Cobb angle and Risser stage blinded in triplicate to examine the reliability of the study measurements. RESULTS: Annualized curve progression (ACP) averaged 6.3 ± 10.4°. ACP varied with length of follow-up: patients with up to 1 year of follow-up had an average ACP of 11.5 ± 17.0°, while those with 1-2 years had 8.2 ± 8.8°, and 2-5 years had 3.7 ± 4.1°, tapering off further from there. Risser stage 0 or 1 was associated with the highest ACP as compared to Risser stage 2-3 or 4-5. Intraclass correlation (ICC) values for Cobb angle measurement and Risser stage designations from four raters measuring 50 patients' measures, blinded and in triplicate, were all > 0.80, signifying a high degree of reliability within and between readers. CONCLUSIONS: Annualized curve progression for 40° and greater curves was not linear over time; it was greatest immediately after a curve reaches 40° and tapered off over the next decade. Immature Risser stage at presentation was strongly associated with increasing ACP at all time frames. LEVEL OF EVIDENCE: Prognostic Level I.

Evidence-Based Medicine Curriculum Improves Pediatric Emergency Fellows' Scores on In-Training Examinations.

OBJECTIVES: The aim of this study was to determine if implementation of our evidence-based medicine (EBM) curriculum had an effect on pediatric emergency medicine fellows' scores on the relevant section of the in-training examination (ITE). METHODS: We obtained deidentified subscores for 22 fellows over 6 academic years for the Core Knowledge in Scholarly Activities (SA) and, as a balance measure, Emergencies Treated Medically sections. We divided the subscores into the following 3 instruction periods: "baseline" for academic years before our current EBM curriculum, "transition" for academic years with use of a research method curriculum with some overlapping EBM content, and "EBM" for academic years with our current EBM curriculum. We analyzed data using the Kruskal-Wallis test, the Mann-Whitney U test, and multivariate mixed-effects linear models. RESULTS: The SA subscore median was higher during the EBM period in comparison with the baseline and transition periods. In contrast, the Emergencies Treated Medically subscore median was similar across instruction periods. Multivariate modeling demonstrated that our EBM curriculum had the following independent effects on the fellows' SA subscore: (1) in comparison with the transition period, the fellows' SA subscore was 21 percentage points higher (P = 0.005); and (2) in comparison to the baseline period, the fellows' SA subscore was 28 percentage points higher during the EBM curriculum instruction period (P < 0.001). CONCLUSIONS: Our EBM curriculum was associated with significantly higher scores on the SA section of the ITE. Pediatric emergency medicine educators could consider using fellows' scores on this section of the ITE to assess the effect of their EBM curricula.

Comparison of the Coagulation Profile of Adolescent Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion With and Without Tranexamic Acid.

STUDY DESIGN: Prospective, observational cohort study. OBJECTIVE: To improve the understanding of coagulation and bleeding mechanisms during spinal deformity surgery. SUMMARY OF BACKGROUND DATA: Fibrinolysis is the mechanism of bleeding for adolescent idiopathic scoliosis undergoing posterior spinal fusion. Antifibrinolytics have become popular; however, literature to support their use remains mixed. The mechanism of action has not been demonstrated. METHODS: The coagulation profile of 88 adolescent idiopathic scoliosis patients undergoing posterior spinal fusion was analyzed. Standard coagulation laboratory investigations and thromboelastograms were drawn hourly through the case. Fifty-eight patients received no antifibrinolytic, whereas 30 patients received tranexamic acid by standardized protocol. The coagulation parameters, estimated blood loss, and transfusion requirements were compared in the two groups. RESULTS: The two cohorts had no differences in demographic or surgical characteristics. Mean age was 13.6 years, 83% were female, a mean of 11.1 levels were fused, and the mean duration of surgery was 209 minutes. The tranexamic acid cohort did not demonstrate a decrease in blood loss. The transfusion rate, however, dropped from 47% in the non-tranexamic acid cohort to 23% in the tranexamic acid cohort (p = .03). Standard coagulation parameters did not differ between the groups. Fibrinolysis was diminished in the tranexamic acid cohort as measured by a Fibrinolysis score (mean maximum value 2.0 without tranexamic acid vs. 0.7 with tranexamic acid, p < .0001) and the lysis percent at 30 minutes by thromboelastogram (elevated to 3.9% without tranexamic acid vs. 1.2% with tranexamic acid at the 3-hour mark, p = .05). CONCLUSIONS: This study provides confirmation of antifibrinolytic activity during posterior spinal fusion for adolescent idiopathic scoliosis. The presented data of fibrinolysis are proposed as standard measurements for future work on controlling blood loss during scoliosis surgery. LEVEL OF EVIDENCE: Level 2, prospective comparative study.

Ten-Year Mortality in the WISE Study (Women's Ischemia Syndrome Evaluation).

BACKGROUND: The WISE study (Women's Ischemia Syndrome Evaluation) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited. METHODS AND RESULTS: Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core laboratory. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular or noncardiovascular by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily black; 25% had a history of diabetes mellitus, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index ≥30. During a median follow-up of 9.5 years (range, 0.2-11.5 years), a total of 184 (20%) died. Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes mellitus, history of smoking, elevated triglycerides, and estimated glomerular filtration rate. CONCLUSIONS: Among women referred for coronary angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death seem to be modifiable by existing therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommended treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study.

BACKGROUND: Sudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study. METHODS AND RESULTS: Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non-SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person-hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P<0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively (P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (P=0.018) and longer corrected QT interval (P=0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD (P=0.033). CONCLUSIONS: SCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.

SRS-22r Scores in Nonoperated Adolescent Idiopathic Scoliosis Patients With Curves Greater Than Forty Degrees.

STUDY DESIGN: Case control comparative series. OBJECTIVE: Describe surgical range adolescent idiopathic scoliosis (AIS) patients electing to forgo surgery and compare health-related quality-of-life outcomes to a similar cohort of operated AIS patients by the same single surgeon. SUMMARY OF BACKGROUND DATA: No data have been published either documenting SRS-22r scores of nonoperated patients with curves ≥40° or comparing these scores to a demographically similar operated cohort. METHODS: Individuals with curves ≥40°, age ≥18 years, and electing to forgo surgery were identified. All patients completed an SRS-22r questionnaire. This nonoperated cohort's SRS-22r scores were compared to those of a large demographically similar cohort operated by the same surgeon. Group differences between the SRS-22r scores were evaluated by comparing these to published Minimal Clinically Important Differences (MCID) for the SRS-22r. RESULTS: One hundred ninety subjects with nonoperated curves were compared to 166 individuals who underwent surgery. The nonoperated cohort averaged 23.5 years of age, averaged 7.7 years since curve reached 40°, and had an average 50° Cobb angle at last follow-up. No statistical significant differences were found between the groups on the Pain, Function, or Mental Health domains of the SRS-22r. Statistically significant differences in favor of the operative cohort were found for self-image, satisfaction, and total score. The observed group differences did not meet the established thresholds for minimal clinically important differences in any of the domain scores, the average total score, or raw scores. CONCLUSION: There are no meaningful clinically significant differences in SRS-22r scores at average 8-year follow-up between AIS patients with curves ≥40° treated with or without surgery. These data in conjunction with an absence of long-term evidence of serious medical consequences with nonsurgical management of curves ≥40° should encourage surgeons to reevaluate the benefits of routine surgical care. LEVEL OF EVIDENCE: 3.

Coagulation Profile of Patients with Adolescent Idiopathic Scoliosis Undergoing Posterior Spinal Fusion.

BACKGROUND: Blood loss and transfusion requirements during posterior spinal fusion for adolescent idiopathic scoliosis remain a concern. The mechanism of bleeding in these patients is poorly characterized. Thromboelastography is a comprehensive test of a patient's coagulation system commonly used in cardiac surgical procedures. It has not been well studied for use in patients with adolescent idiopathic scoliosis. METHODS: A prospective, observational study of the coagulation profile of patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion is presented. Healthy patients with adolescent idiopathic scoliosis without a bleeding abnormality were analyzed during posterior spinal fusion. Standard coagulation laboratory and thromboelastogram measures were obtained at the time of the incision and at 1-hour intervals during the surgical procedure. Laboratory values were analyzed in relation to outcomes such as bleeding, transfusion, and a fibrinolysis score. RESULTS: Fifty-eight patients were observed. Eighty-one percent of patients were female, the mean age was 13.5 years, a mean of 11.1 levels were fused, the median estimated blood loss was 645 mL, and 47% of patients received blood products. Overall, laboratory values remained stable throughout the surgical procedure. Mild increases in prothrombin time and partial thromboplastin time were observed, and platelets remained stable. From thromboelastogram analysis, an acceleration of clot formation (decreased reaction time) and a slight increase in clot lysis (increased lysis percentage at 30 minutes) were observed. A fibrinolysis score compiled from the presence of fibrin degradation products, the presence of D-dimers, and increased prothrombin time rose steadily over surgical time. The fibrinolysis score was predictive of both transfusion and greater estimated blood loss per level. CONCLUSIONS: The stress of posterior spinal fusion induces a hypercoagulable state in patients with adolescent idiopathic scoliosis. Over the first 2 hours of a surgical procedure, varying degrees of fibrinolysis develop. Platelets and coagulation factors are not depleted. Our data support the use of antifibrinolytic therapy for patients with adolescent idiopathic scoliosis.

Circulating progenitor cells and coronary microvascular dysfunction: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD).

BACKGROUND AND AIMS: Ischemia stimulates a reparative response resulting in mobilization of circulating progenitor cells (CPCs). We hypothesized that women with chronic myocardial ischemia from coronary microvascular disease (CMD) will mobilize CPCs. METHODS: In 123 women with ischemic symptoms and signs but no obstructive coronary artery disease (CAD) enrolled in the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD), we measured coronary flow reserve (CFR) in response to intracoronary adenosine. Peripheral blood CPCs were measured using flow cytometry for expression of CD34, CD133, CXCR4, and VEGFR2. RESULTS: Subjects were 53 ± 11 years, BMI 30 ± 8; 44% hypertensive, 11% diabetic, 23% hyperlipidemic and 7% smokers. Lower CFR correlated inversely with higher levels of hematopoietic-enriched CD34+ (r = -0.23, p = 0.011), CD34+/CD133+ (r = -0.24, p = 0.008), and CD34+/CXCR4+ (r = -0.19, p = 0.036) cells. In multivariable regression analyses, after adjusting for traditional cardiovascular risk factors, lower CFR remained significantly associated with elevated levels of CD34+ (ß -0.18, p = 0.042), CD34+/CD133+ (ß -0.24, p = 0.036), and CD34+/CXCR4+ (ß -0.22, p = 0.050) cells. We found no association between CFR and CD34+/VEGFR2+ cells. CONCLUSIONS: In women with non-obstructive CAD, impaired CFR is associated with higher levels of CPCs, suggesting that chronic myocardial ischemia from CMD stimulates CPC mobilization. The functional significance of elevated CPCs in these subjects requires further investigation as a potential biomarker and treatment target.

Psychosocial predictors of long-term mortality among women with suspected myocardial ischemia: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

This paper evaluated long-term associations between psychosocial factors and premature mortality among women with suspected coronary artery disease (CAD). We tracked total mortality events over a median 9.3 years in a cohort of 517 women [baseline mean age = 58.3 (11.4) years]. Baseline evaluations included coronary angiography, psychosocial testing, and CAD risk factors. Measures included the Spielberger Trait Anxiety Scale, Beck Depression Inventory, self-rated health, and Social Network Index. Cox regression analysis was used to assess relationships. Covariates included age, CAD risk factors, and CAD severity. BDI scores (HR 1.09, 95 % CI 1.02-1.15), STAI scores (HR .86, 95 % CI .78-.93), and very good self-rated health (relative to the poor self-rated health group; HR .33, 95 % CI .12-.96) each independently predicted time to mortality outcomes in the combined model. SNI scores (HR .91, 95 % CI .81-1.06) and other self-rated health categories (i.e., fair, good, and excellent categories) were not significant mortality predictors after adjusting for other psychosocial factors. These results reinforce and extend prior psychosocial research in CAD populations.

A Pilot Study of Continuous Infusion of Mycophenolate Mofetil for Prophylaxis of Graft-versus-Host-Disease in Pediatric Patients.

Mycophenolate mofetil (MMF), an ester prodrug of mycophenolic acid (MPA), is used increasingly for graft-versus-host disease (GVHD) prophylaxis. Empiric fixed-dose-escalation strategies in pediatric hematopoietic cell transplantation (HCT) recipients have failed to achieve target MPA exposure. We evaluated the safety and feasibility of a pharmacokinetics-based dosing approach using a novel continuous infusion (CI) method of administration of MMF in pediatric HCT recipients. All patients received a myeloablative conditioning with cyclosporine A and MMF for GVHD prophylaxis. MMF was initiated on day 0 at a dose of 15 mg/kg every 8 hours. Based on steady-state pharmacokinetics, MMF was converted to CI to target a total MPA AUC(0-24) of 40 to 80 µg·hour/mL. The MMF dose was adjusted to maintain a total MPA steady-state concentration (Css) of 1.7 to 3.3 µg/mL. During the CI schedule, MPA AUC(0-24) was maintained at a mean of 40.1 µg·hour/mL (range, 20.6 to 63.8), and 17 of 19 patients (89%) achieved MPA Css within target of 1.7 to 3.3 µg/mL. Eighteen of 19 patients (95%) achieved neutrophil engraftment at a median of 13 days (range, 8 to 41) post-transplant and platelet engraftment at 39 days (range, 17 to 298) days post-transplant. Six of 18 assessable patients (33%) developed stages II to IV acute GVHD and 2 of 15 (13%) developed chronic GVHD. The MMF dose was reduced in 9 patients due to gastrointestinal symptoms (n = 6), low blood counts (n = 4), and viral infection (n = 3). Five patients with acute lymphoblastic leukemia relapsed, of whom 4 have died. Fifteen of 19 patients are alive with a median follow-up of 2.4 years (range, .4 to 4.9), with 3-year event-free and overall survival rates of 68% and 79%, respectively. In this pilot study of pharmacokinetically directed MMF dosing, we observed no toxic deaths, excellent engraftment, and low rates of grades III to IV acute and chronic GVHD. We found significantly lower half-life and higher drug clearance in pediatric HCT recipients compared with stable pediatric renal transplant patients or adult transplant patients. This regimen deserves further validation in a larger cohort of pediatric patients undergoing myeloablative transplantation.

Depression, dietary habits, and cardiovascular events among women with suspected myocardial ischemia.

BACKGROUND: Dietary habits and depression are associated with cardiovascular disease risk. Patients with depression often report poor eating habits, and dietary factors may help explain commonly observed associations between depression and cardiovascular disease. METHODS: From 1996 to 2000, 936 women were enrolled in the Women's Ischemia Syndrome Evaluation at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (median follow-up, 5.9 years) for adverse outcomes (cardiovascular disease death, heart failure, myocardial infarction, stroke). Participants completed a protocol including coronary angiography (coronary artery disease severity) and depression assessments (Beck Depression Inventory scores, antidepressant use, and depression treatment history). A subset of 201 women (mean age, 58.5 years; standard deviation, 11.4) further completed the Food Frequency Questionnaire for Adults (1998 Block). We extracted daily fiber intake and daily servings of fruit and vegetables as measures of dietary habits. RESULTS: In separate Cox regression models adjusted for age, smoking, and coronary artery disease severity, Beck Depression Inventory scores (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.10), antidepressant use (HR, 2.4; 95% CI, 1.01-5.9), and a history of treatment for depression (HR, 2.4; 95% CI, 1.1-5.3) were adversely associated with time to cardiovascular disease outcomes. Fiber intake (HR, 0.87; 95% CI, 0.78-0.97) and fruit and vegetable consumption (HR, 0.36; 95% CI, 0.19-0.70) were associated with a decreased time to cardiovascular disease event risk. In models including dietary habits and depression, fiber intake and fruit and vegetable consumption remained associated with time to cardiovascular disease outcomes, whereas depression relationships were reduced by 10% to 20% and nonsignificant. CONCLUSIONS: Among women with suspected myocardial ischemia, we observed consistent relationships among depression, dietary habits, and time to cardiovascular disease events. Dietary habits partly explained these relationships. These results suggest that dietary habits should be included in future efforts to identify mechanisms linking depression to cardiovascular disease.

Anxiety associations with cardiac symptoms, angiographic disease severity, and healthcare utilization: the NHLBI-sponsored Women's Ischemia Syndrome Evaluation.

BACKGROUND: Anxiety is common among patients presenting with suspected coronary artery disease (CAD). In a sample of women with signs and symptoms of ischemia, we examined three anxiety markers as predictors of CAD endpoints including: 1) cardiac symptom indicators; 2) angiographic CAD severity; and 3) healthcare utilization (cardiac hospitalizations and 5-year cardiovascular [CVD] healthcare costs). METHODS: Participants completed a baseline protocol including coronary angiogram, cardiac symptoms, psychosocial measures and a median 5.9-year follow-up to track hospitalizations. We calculated CVD costs based on cardiac hospitalizations, treatment visits, and CVD medications. Anxiety measures included anxiolytic medication use, Spielberger Trait Anxiety Inventory (STAI) scores, and anxiety disorder treatment history. RESULTS: The sample numbered 514 women with anxiety measure data and covariates (mean age=57.5 [11.1]). One in five (20.4%) women reported using anxiolytic agents. Anxiety correlated with cardiac symptom indicators (anxiolytic use with nighttime angina and nitroglycerine use; STAI scores and anxiety disorder treatment history with nighttime angina, shortness of breath, and angina frequency). Anxiety disorder treatment history (but not STAI scores or anxiolytics) predicted less severe CAD. Anxiolytic use (but not STAI scores or anxiety disorder treatment history) predicted hospitalizations for chest pain and coronary catheterization (HRs=2.0, 95% CIs=1.1-4.7). Anxiety measures predicted higher 5-year CVD costs (+9.0-42.7%) irrespective of CAD severity. CONCLUSIONS: Among women with signs and symptoms of myocardial ischemia, anxiety measures predict cardiac endpoints ranging from cardiac symptom severity to healthcare utilization. Based on these findings, anxiety may warrant greater consideration among women with suspected CAD.

Structure, process, and satisfaction with obstetricians: an analysis of mainland Puerto Ricans.

This study examines various dimensions of satisfaction with obstetricians among mainland Puerto Ricans using data from a survey administered to a representative sample of 1,219 Puerto Rican mothers. The results indicate that the majority of Puerto Rican women are satisfied with their obstetricians, but they are not typically "extremely" satisfied. Moreover, satisfaction is influenced by the structure of care, the process of care, and the outcome of care. Two aspects of process that are especially important are the continuity and content of care. Although satisfaction is not generally associated with the ethnicity or the gender of physicians, some evidence suggests that patients who utilize public facilities or lack continuity of care tend to be more satisfied if they have a female physician.