A metabolic pathway for bile acid dehydroxylation by the gut microbiome.

The gut microbiota synthesize hundreds of molecules, many of which influence host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at concentrations of around 500 µM and are known to block the growth of Clostridium difficile1, promote hepatocellular carcinoma2 and modulate host metabolism via the G-protein-coupled receptor TGR5 (ref. 3). More broadly, DCA, LCA and their derivatives are major components of the recirculating pool of bile acids4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Nonetheless, despite the clear impact of DCA and LCA on host physiology, an incomplete knowledge of their biosynthetic genes and a lack of genetic tools to enable modification of their native microbial producers limit our ability to modulate secondary bile acid levels in the host. Here we complete the pathway to DCA and LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the eight-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a nonproducing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool.

Remote control of mechanochemical reactions under physiological conditions using biocompatible focused ultrasound.

External control of chemical reactions in biological settings with spatial and temporal precision is a grand challenge for noninvasive diagnostic and therapeutic applications. While light is a conventional stimulus for remote chemical activation, its penetration is severely attenuated in tissues, which limits biological applicability. On the other hand, ultrasound is a biocompatible remote energy source that is highly penetrant and offers a wide range of functional tunability. Coupling ultrasound to the activation of specific chemical reactions under physiological conditions, however, remains a challenge. Here, we describe a synergistic platform that couples the selective mechanochemical activation of mechanophore-functionalized polymers with biocompatible focused ultrasound (FUS) by leveraging pressure-sensitive gas vesicles (GVs) as acousto-mechanical transducers. The power of this approach is illustrated through the mechanically triggered release of covalently bound fluorogenic and therapeutic cargo molecules from polymers containing a masked 2-furylcarbinol mechanophore. Molecular release occurs selectively in the presence of GVs upon exposure to FUS under physiological conditions. These results showcase the viability of this system for enabling remote control of specific mechanochemical reactions with spatiotemporal precision in biologically relevant settings and demonstrate the translational potential of polymer mechanochemistry.

Mechanical Force Enables an Anomalous Dual Ring-Opening Reaction of Naphthodipyran.

Multimodal mechanophores that exhibit complex mechanochromic behavior beyond the typical binary response are capable of distinguishing between multiple stress states through discrete changes in color. Naphthodipyran photoswitches contain two pyran rings fused to a central naphthalene core and represent a potentially promising framework for multimodal reactivity. However, the concurrent ring opening of both pyran moieties has previously proven inaccessible via photochemical activation. Here, we demonstrate that mechanical force supplied to naphthodipyran through covalently linked polymer chains generates the elusive dual ring-opened dimerocyanine product with unique near-infrared absorption properties. Trapping with boron trifluoride renders the merocyanine dyes thermally persistent and reveals apparent sequential ring-opening behavior that departs from the reactivity of previously studied mechanophores under the high strain rates imposed by ultrasound-induced solvodynamic chain extension.

Amino acid divergence in the ligand-binding pocket of Vibrio LuxR/HapR proteins determines the efficacy of thiophenesulfonamide inhibitors.

The quorum-sensing signaling systems in Vibrio bacteria converge to control levels of the master transcription factors LuxR/HapR, a family of highly conserved proteins that regulate gene expression for bacterial behaviors. A compound library screen identified 2-thiophenesulfonamide compounds that specifically inhibit Vibrio campbellii LuxR but do not affect cell growth. We synthesized a panel of 50 thiophenesulfonamide compounds to examine the structure-activity relationship effects on Vibrio quorum sensing. The most potent molecule identified, PTSP (3-phenyl-1-(thiophen-2-ylsulfonyl)-1H-pyrazole), inhibits quorum sensing in multiple strains of V. vulnificus, V. parahaemolyticus, and V. campbellii at nanomolar concentrations. However, thiophenesulfonamide inhibition efficacy varies significantly among Vibrio species: PTSP is most inhibitory against V. vulnificus SmcR, but V. cholerae HapR is completely resistant to all thiophenesulfonamides tested. Reverse genetics experiments show that PTSP efficacy is dictated by amino acid sequence in the putative ligand-binding pocket: F75Y and C170F SmcR substitutions are each sufficient to eliminate PTSP inhibition. Further, in silico modeling distinguished the most potent thiophenesulfonamides from less-effective derivatives. Our results revealed the previously unknown differences in LuxR/HapR proteins that control quorum sensing in Vibrio species and underscore the potential for developing thiophenesulfonamides as specific quorum sensing-directed treatments for Vibrio infections.

Changes in Pain Catastrophizing and Fear-Avoidance Beliefs as Mediators of Early Physical Therapy on Disability and Pain in Acute Low-Back Pain: A Secondary Analysis of a Clinical Trial.

OBJECTIVE: The Fear-Avoidance Model (FAM) of chronic pain posits that pain catastrophizing and fear-avoidance beliefs are prognostic for disability and chronicity. In acute low-back pain, early physical therapy (PT) is effective in reducing disability in some patients. How early PT impacts short- and long-term changes in disability for patients with acute pain is unknown. Based on the FAM, we hypothesized that early reductions in pain catastrophizing and fear-avoidance beliefs would mediate early PT's effect on changes in disability (primary outcome) and pain intensity (secondary outcome) over 3 months and 1 year. SUBJECTS: Participants were 204 patients with low-back pain of <16 days duration, who enrolled in a clinical trial (NCT01726803) comparing early PT sessions or usual care provided over 4 weeks. METHODS: Patients completed the Pain Catastrophizing Scale (PCS), Fear-Avoidance Beliefs Questionnaire (FABQ work and physical activity scales), and outcomes (Oswestry Disability Index and Numeric Pain Rating Scale) at baseline, 4 weeks, 3 months, and 1 year. We applied longitudinal mediation analysis with single and multiple mediators. RESULTS: Early PT led to improvements in disability and pain over 3 months but not 1 year. In the single mediator model, 4-week reductions in pain catastrophizing mediated early PT's effects on 3-month disability and pain intensity improvements, explaining 16% and 22% of the association, respectively, but the effects were small. Pain catastrophizing and fear-avoidance beliefs did not jointly mediate these associations. CONCLUSIONS: In acute low-back pain, early PT may improve disability and pain outcomes at least partly through reducing patients' catastrophizing.

Physical Therapy Referral From Primary Care for Acute Back Pain With Sciatica : A Randomized Controlled Trial.

BACKGROUND: Few studies have examined primary care management for acute sciatica, including referral to physical therapy. OBJECTIVE: To evaluate whether early referral to physical therapy reduced disability more than usual care (UC) alone for patients with acute sciatica. DESIGN: Randomized controlled clinical trial. (ClinicalTrials.gov: NCT02391350). SETTING: 2 health care systems in Salt Lake City, Utah. PATIENTS: 220 adults aged 18 to 60 years with sciatica of less than 90 days' duration who were making an initial primary care consultation. INTERVENTION: All participants received imaging and medication at the discretion of the primary care provider before enrollment. A total of 110 participants randomly assigned to UC were provided 1 session of education, and 110 participants randomly assigned to early physical therapy (EPT) were provided 1 education session and then referred for 4 weeks of physical therapy, including exercise and manual therapy. MEASUREMENTS: The primary outcome was the Oswestry Disability Index (OSW) score after 6 months. Secondary outcomes were pain intensity, patient-reported treatment success, health care use, and missed workdays. RESULTS: Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, -5.4 points [95% CI, -9.4 to -1.3 points]; P = 0.009). The OSW and several secondary outcomes favored EPT after 4 weeks. After 1 year, between-group differences favored EPT for the OSW (relative difference, -4.8 points [CI, -8.9 to -0.7 points]) and back pain intensity (relative difference, -1.0 points [CI, -1.6 to -0.4 points]). The EPT group was more likely to self-report treatment success after 1 year (45.2%) than the UC group (27.6%) (relative risk, 1.6 [CI, 1.1 to 2.4]). There were no significant differences in health care use or missed workdays. LIMITATION: The patients and providers were unblinded, and specific physical therapy interventions responsible for effects could not be determined. CONCLUSION: Referral from primary care to physical therapy for recent-onset sciatica improved disability and other outcomes compared with UC. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Generation of an Elusive Permanent Merocyanine via a Unique Mechanochemical Reaction Pathway.

We report the discovery of a 2H-naphtho[1,2-b]pyran mechanophore that produces a permanent merocyanine dye upon mechanochemical activation, in contrast to the reversible product generated photochemically. Experiments suggest that the irreversibility of the mechanically generated merocyanine is due to a unique reaction in which the scission of an ester C-O bond reveals a ß-hydroxy ketone that locks the merocyanine through an intramolecular H-bonding interaction. In addition to demonstrating the reactivity using solution-phase ultrasonication, permanent merocyanine generation is also achieved in solid polymeric materials. The permanent coloration achieved with the naphthopyran mechanophore affords unique opportunities for sensing and force-recording applications as well as fundamental studies limited by the reversibility of typical colorimetric force probes.

The Relationship Between Neighborhood Deprivation and Perceived Changes for Pain-Related Experiences Among US Patients with Chronic Low Back Pain During the COVID-19 Pandemic.

OBJECTIVE: Disruptions caused by the COVID-19 pandemic could disproportionately affect the health of vulnerable populations, including patients experiencing persistent health conditions (i.e., chronic pain), along with populations living within deprived, lower socioeconomic areas. The current cross-sectional study characterized relationships between neighborhood deprivation and perceived changes in pain-related experiences during the COVID-19 pandemic (early-September to mid-October 2020) for adult patients (N = 97) with nonspecific chronic low back pain. METHODS: We collected self-report perceived experiences from participants enrolled in an ongoing pragmatic randomized trial across medical centers within the Salt Lake City, Utah and Baltimore, Maryland metropolitans. The Area Deprivation Index (composite of 17 US Census deprivation metrics) reflected neighborhood deprivation based on participants' zip codes. RESULTS: Although those living in the neighborhoods with greater deprivation endorsed significantly poorer physical (pain severity, pain interference, physical functioning), mental (depression, anxiety), and social health during the pandemic, there were no significant differences for perceived changes in pain-related experiences (pain severity, pain interference, sleep quality) between levels of neighborhood deprivation since the onset of the pandemic. However, those in neighborhoods with greater deprivation endorsed disproportionately worse perceived changes in pain coping, social support, and mood since the pandemic. CONCLUSIONS: The current findings offer evidence that changes in pain coping during the pandemic may be disproportionately worse for those living in deprived areas. Considering poorer pain coping may contribute to long-term consequences, the current findings suggest the need for further attention and intervention to reduce the negative effect of the pandemic for such vulnerable populations.

Force-Dependent Multicolor Mechanochromism from a Single Mechanophore.

We report a bis-naphthopyran mechanophore that exhibits force-dependent changes in visible absorption. A series of polymers incorporating a chain-centered bis-naphthopyran mechanophore was synthesized and mechanically activated using ultrasonication. By varying the length of the polymer chains, the force delivered to the mechanophore is modulated systematically. We demonstrate that the relative distribution of two distinctly colored merocyanine products is altered predictably with different magnitudes of applied force, resulting in gradient multicolor mechanochromism. The mechanochemical reactivity of bis-naphthopyran is supported by density functional theory calculations and described by a theoretical model that provides insight into the force-color relationship.

Mechanochemical Regulation of a Photochemical Reaction.

We introduce the concept of mechanochemically gated photoswitching. Mechanical regulation of a photochemical reaction is exemplified using a newly designed mechanophore based on a cyclopentadiene-maleimide Diels-Alder adduct. Ultrasound-induced mechanical activation of the photochemically inert mechanophore in polymers generates a diarylethene photoswitch via a retro-[4 + 2] cycloaddition reaction that photoisomerizes between colorless and colored states upon exposure to UV and visible light. Control experiments demonstrate the thermal stability of the cyclopentadiene-maleimide adduct and confirm the mechanical origin of the "unlocked" photochromic reactivity. This technology holds promise for applications such as lithography and stress-sensing, enabling the mechanical history of polymeric materials to be recorded and read on-demand.

Diffusion-Weighted Imaging and Post-contrast Enhancement in Differentiating Optic Neuritis and Non-arteritic Anterior Optic Neuropathy.

Non-arteritic anterior ischaemic optic neuropathy (NAION) and optic neuritis (ON) may be difficult to distinguish early in their disease courses. Our goal was to determine if specific magnetic resonance imaging characteristics differentiate acute NAION from ON. Neuroradiologists, masked to diagnosis, reviewed the diffusion-weighted imaging (DWI) and post-contrast enhancement (PCE) characteristics of the optic nerve in 140 eyes. PCE and DWI signals of the optic disc alone did not discriminate between NAION and ON. After taking age and sex into consideration, only DWI and PCE of the intraorbital segment of the optic nerve differentiated the two, with ON having the increased likelihood of these findings. Isolated PCE without DWI signal at the optic disc, however, was 100% specific for NAION. This may be the most specific way to radiographically differentiate between NAION and ON in the acute setting.

The safety of achieved iron stores and their effect on IV iron and ESA use: post-hoc results from a randomized trial of ferric citrate as a phosphate binder in dialysis
.

Iron stores assuring optimal efficacy/safety for erythropoiesis are unknown in the dialysis population. Using multicenter trial data, we related safety profiles, erythropoiesis-stimulating agent (ESA), and intravenous iron dosing to achieved iron stores in 441 subjects randomized 2 : 1 to ferric citrate or active control as their phosphate binder over 52 weeks. Intravenous iron was given at each site's discretion if ferritin ≤ 1,000 ng/mL and transferrin saturation ≤ 30%. Multivariable time-dependent Cox regression jointly related the primary safety outcome (composite of cardiac, infection, gastrointestinal, and hepatobiliary serious adverse events) to moving averages of ferritin and transferrin saturation over the preceding 90 days with covariate adjustment. Multivariable generalized estimating equations related elevated ESA and intravenous iron doses to trailing 90-day averages of ferritin and transferrin saturation with covariate adjustment. The adjusted hazard ratio for the safety composite per 10% increase in transferrin saturation was 0.84 (95% confidence interval 0.68 - 1.02, p = 0.08) and 1.09 (0.86 - 1.35, p = 0.48) per 400 ng/mL increase in ferritin. The adjusted hazard ratio for the safety composite was 0.50 (0.29 - 0.88, p = 0.016) for the highest transferrin saturation tertile vs. the lowest. Adjusted odds ratios for higher intravenous iron dose were lower in the highest (0.23 [0.16 - 0.35], p < 0.001) and middle transferrin saturation tertile (0.42 [0.31 - 0.57], p < 0.001) vs. lowest. Incidence of elevated ESA dose was lower in the highest transferrin saturation tertile (p = 0.01). Ferritin did not predict clinical events or ESA dose. Transferrin saturation may be a better marker than serum ferritin to judge optimal iron stores in dialysis patients. Transferrin saturations > 34% are safe and provide maximal efficacy.
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A multi-institutional study of factors affecting resource utilisation following the Fontan operation.

The few studies evaluating data on resource utilisation following the Fontan operation specifically are outdated. We sought to evaluate resource utilisation and factors associated with increased resource use after the Fontan operation in a contemporary, large, multi-institutional cohort. This retrospective cohort study of children who had the Fontan between January, 2004 and June, 2013 used the Pediatric Health Information Systems Database. Generalised linear regression analyses evaluated factors associated with resource use. Of 2187 Fontan patients included in the study, 62% were males. The median age at Fontan was 3.2 years (inter-quartile range (IQR): 2.6-3.8). The median length of stay following the Fontan was 9 days (IQR: 7-14). The median costs and charges in 2012 dollars for the Fontan operation were $93,900 (IQR: $67,800-$136,100) and $156,000 (IQR: $112,080-$225,607), respectively. Postoperative Fontan mortality (30 days) was 1% (n=21). Factors associated with increased resource utilisation included baseline and demographic factors such as region, race, and renal anomaly, factors at the bidirectional Glenn such as seizures, valvuloplasty, and surgical volume, number of admissions between the bidirectional Glenn and the Fontan, and factors at the Fontan such as surgical volume and age at Fontan. The most strongly associated factors for both increased Fontan length of stay and increased Fontan charges were number of bidirectional Glenn to Fontan admissions (p<0.001) and Fontan surgical volume per year (p<0.001). As patient characteristics and healthcare-related delivery variables accounted for most of the factors predicting increased resource utilisation, changes should target healthcare delivery factors to reduce costs in this resource-intensive population.

Factors Influencing Occupational Therapists' Decision to Supervise Fieldwork Students.

The purpose of this study was to identify factors that influence the decision to supervise a Level II occupational therapy fieldwork student. A survey was sent to occupational therapists identified from licensure boards and alumni rosters, including those who have and have not supervised students (n = 548). The results identified both positive and negative influences along with predictive factors of supervising a student. While positive factors included continuing education units, education on fieldwork expectations, their own fieldwork experiences, shared supervision, and access to educational resources, negative influences consisted of: job responsibilities, caseload, productivity standards, working part-time, and fear of failing a student. The discussion focuses on how to address the needs of the clinician and facilitate fieldwork placement.

Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture.

BACKGROUND: Posttraumatic osteoarthritis (OA) is a variant of OA that can develop after articular injury. Although the mechanism(s) of posttraumatic OA are uncertain, the presence and impact of postinjury proteolytic enzymes on articular cartilage remain unknown. To our knowledge, there are no studies that evaluate the presence of matrix metalloproteinases (MMPs) or aggrecan degradation after articular fracture. QUESTIONS/PURPOSES: (1) Are MMP concentrations and aggrecan degradation elevated after intraarticular fracture? (2) Are MMP concentrations and aggrecan degradation greater in high-energy injuries compared with low-energy injuries? (3) Do the concentrations of these biomarkers remain elevated at a secondary aspiration? METHODS: Between December 2011 and June 2013, we prospectively enrolled patients older than 18 years of age with acute tibial plateau fracture. Exclusion criteria included age older than 60 years, preexisting knee OA, injury greater than 24 hours before evaluation, contralateral knee injury, history of autoimmune disease, open fracture, and non-English-speaking patients. During the enrollment period, we enrolled 45 of the 91 (49%) tibial plateau fractures treated at our facility. Knee synovial fluid aspirations were obtained from both the injured and uninjured knees; two patients received aspirations in the emergency department and the remaining patients received aspirations in the operating room. Twenty patients who underwent spanning external fixator followed by definitive fixation were aspirated during both surgical procedures. MMP-1, -2, -3, -7, -9, -10, -12, and -13 concentrations were quantified using multiplex assays. Aggrecan degradation was quantified using sandwich enzyme-linked immunosorbent assay. RESULTS: There were higher concentrations of MMP-1 (3.89 ng/mL [95% confidence interval {CI}, 2.37-6.37] versus 0.37 ng/mL [95% CI, 0.23-0.61], p < 0.001), MMP-3 (457.35 ng/mL [95% CI, 274.5-762.01] versus 129.17 ng/mL [95% CI, 77.01-216.66], p < 0.001), MMP-9 (6.52 ng/mL [95% CI, 3.86-11.03] versus 0.96 ng/mL [95% CI, 0.56-1.64], p < 0.001), MMP-10 (0.52 ng/mL [95% CI, 0.40-0.69] versus 0.23 ng/mL [95% CI, 0.17-0.30], p < 0.001), and MMP-12 (0.18 ng/mL [95% CI, 0.14-0.23] versus 0.10 ng/mL [95% CI, 0.0.081-0.14], p = 0.005) in injured knees compared with uninjured knees. There was not a detectable difference in MMP concentrations or aggrecan degradation between high- and low-energy injuries. MMP-1 (53.25 versus 3.89 ng/mL, p < 0.001), MMP-2 (76.04 versus 0.37 ng/mL, p < 0.001), MMP-3 (1250.62 versus 457.35 ng/mL, p = 0.002), MMP-12 (1.37 versus 0.18, p < 0.001), MMP-13 (0.98 versus 0.032 ng/mL, p < 0.001), and aggrecan degradation (0.58 versus 0.053, p < 0.001) were increased at the second procedure (mean, 9.5 days; range, 3-21 days) as compared with the initial procedure. CONCLUSIONS: Because MMPs and aggrecan degradation are elevated after articular fracture, future studies are necessary to evaluate the impact of elevated MMPs and aggrecan degradation on human articular cartilage. CLINICAL RELEVANCE: If further clinical followup can demonstrate a relationship between posttraumatic OA and elevated MMPs and aggrecan degradation, they may provide potential for therapeutic targets to prevent or delay the destruction of the joint. Additionally, these markers may offer prognostic information for patients.

Early Physical Therapy vs Usual Care in Patients With Recent-Onset Low Back Pain: A Randomized Clinical Trial.

IMPORTANCE: Low back pain (LBP) is common in primary care. Guidelines recommend delaying referrals for physical therapy. OBJECTIVE: To evaluate whether early physical therapy (manipulation and exercise) is more effective than usual care in improving disability for patients with LBP fitting a decision rule. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial with 220 participants recruited between March 2011 and November 2013. Participants with no LBP treatment in the past 6 months, aged 18 through 60 years (mean age, 37.4 years [SD, 10.3]), an Oswestry Disability Index (ODI) score of 20 or higher, symptom duration less than 16 days, and no symptoms distal to the knee in the past 72 hours were enrolled following a primary care visit. INTERVENTIONS: All participants received education. Early physical therapy (n = 108) consisted of 4 physical therapy sessions. Usual care (n = 112) involved no additional interventions during the first 4 weeks. MAIN OUTCOMES AND MEASURES: Primary outcome was change in the ODI score (range: 0-100; higher scores indicate greater disability; minimum clinically important difference, 6 points) at 3 months. Secondary outcomes included changes in the ODI score at 4-week and 1-year follow-up, and change in pain intensity, Pain Catastrophizing Scale (PCS) score, fear-avoidance beliefs, quality of life, patient-reported success, and health care utilization at 4-week, 3-month, and 1-year follow-up. RESULTS: One-year follow-up was completed by 207 participants (94.1%). Using analysis of covariance, early physical therapy showed improvement relative to usual care in disability after 3 months (mean ODI score: early physical therapy group, 41.3 [95% CI, 38.7 to 44.0] at baseline to 6.6 [95% CI, 4.7 to 8.5] at 3 months; usual care group, 40.9 [95% CI, 38.6 to 43.1] at baseline to 9.8 [95% CI, 7.9 to 11.7] at 3 months; between-group difference, -3.2 [95% CI, -5.9 to -0.47], P = .02). A significant difference was found between groups for the ODI score after 4 weeks (between-group difference, -3.5 [95% CI, -6.8 to -0.08], P = .045]), but not at 1-year follow-up (between-group difference, -2.0 [95% CI, -5.0 to 1.0], P = .19). There was no improvement in pain intensity at 4-week, 3-month, or 1-year follow-up (between-group difference, -0.42 [95% CI, -0.90 to 0.02] at 4-week follow-up; -0.38 [95% CI, -0.84 to 0.09] at 3-month follow-up; and -0.17 [95% CI, -0.62 to 0.27] at 1-year follow-up). The PCS scores improved at 4 weeks and 3 months but not at 1-year follow-up (between-group difference, -2.7 [95% CI, -4.6 to -0.85] at 4-week follow-up; -2.2 [95% CI, -3.9 to -0.49] at 3-month follow-up; and -0.92 [95% CI, -2.7 to 0.61] at 1-year follow-up). There were no differences in health care utilization at any point. CONCLUSIONS AND RELEVANCE: Among adults with recent-onset LBP, early physical therapy resulted in statistically significant improvement in disability, but the improvement was modest and did not achieve the minimum clinically important difference compared with usual care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01726803.

Yield of cardiac magnetic resonance imaging as an adjunct to echocardiography in young infants with congenital heart disease.

Echocardiography provides adequate preoperative imaging for most young infants with congenital heart disease (CHD). When anatomic details require further clarification, cardiac magnetic resonance imaging (CMRI) may be useful but adds the risks of sedation or general anesthesia for a vulnerable population. This study aimed to determine the safety of CMRI and its yield of additional significant information for this population. The study identified all infants age 90 days or younger with preoperative echocardiography and a CMRI from the period 2002-2012. Indications, complications, and imaging results were collected. The additional CMRI information was defined as "significant" if it altered surgical management or "not significant" if it did not. Associations between indications for CMRI and the likelihood of new significant findings were sought. For 137 infants (58% male), CMRI was performed at a median age of 5 days (range, 0-89 days). The CMRI yielded additional information for 76% (104/137) of the patients. The additional findings were significant for 69% (72/104) of these patients. The incidence of significant new findings was similar among indication categories. All the infants were intubated. Complications occurred for 5% of the patients, including one subject with a bradycardic event that prevented completion of the exam and six patients with transient vital sign changes that allowed exam completion. More than 50% of young infants with CHD who underwent preoperative CMRI had new findings affecting surgical management. Among these patients, CMRI-associated complications were few and predominantly minor for intubated infants. Further studies to determine standard preoperative criteria for the use of CMRI for infants with CHD may help to define appropriate cost-effective use of this diagnostic method.

Stillbirth gestational age as a predictor of recurrence risk.

OBJECTIVE: We evaluated risk of subsequent stillbirth (SB) according to gestational age at initial SB. STUDY DESIGN: We retrospectively reviewed a cohort of women delivering a singleton SB with at least one subsequent pregnancy. Relative risks (RRs) were calculated using an initial SB gestational age of 36 to < 40 weeks as the referent. Multivariable logistic regression accounted for potential confounders. RESULTS: In all, 2,887 mothers and 5,090 subsequent births met inclusion criteria. For the immediately next pregnancy, the linear trend for gestational age was not significant (RR 0.41; 95% confidence interval [CI] 0.03 to 5.53). However, women with index SBs occurring between 20 and 23(6/7) weeks' gestation had a RR for subsequent stillbirth of 2.9 (95% CI 1.2 to 7.1). When including subsequent pregnancies, the test for trend for gestational age was nonsignificant (RR 1.5; 95% CI 0.3 to 8.7). However, women suffering a stillbirth between 20(0/7) and 23(6/7) weeks' gestation in the index pregnancy had an almost threefold increase in the risk of subsequent stillbirth. Women suffering an index stillbirth between 28(0/7) and 31(6/7) weeks' and after 40 weeks' gestation had a 2.5- to 3.5-fold increased risk of subsequent SB. CONCLUSIONS: Gestational age at initial SB predicts risk of recurrent SB. This effect is most pronounced in women with very preterm or with postterm pregnancies.

Quality of life after intra-arterial therapy for acute ischemic stroke.

Few data exist about health-related quality of life outcomes after intra-arterial therapy (IAT) for acute ischemic stroke (AIS). We assessed stroke-specific quality of life (SS-QOL) in survivors of stroke after IAT. Consecutive patients undergoing IAT for AIS from 2005 to 2010 were retrospectively identified via an institutional database. SS-QOL (using the SS-QOL score) and disability status (modified Rankin Scale [mRS]) were prospectively assessed via mailed questionnaire. We analyzed quality of life (QOL) scores by domain and summary score, with a summary score of 4 or more defined as a good outcome. Analysis of variance (ANOVA) was used to model the effect of final recanalization status, stroke severity, and mRS on total QOL score. ANOVA and Pearson correlations were used to test the association between stroke severity/mRS and QOL/time since stroke, respectively. Of 99 patients with AIS, 61 responded, yielding 11 interim deaths, 7 incomplete surveys, and 43 complete surveys for analysis. Among responding survivors, overall QOL score was 3.9 (standard deviation 0.7); 77% of these reported good QOL. Scores were higher in recanalized patients in 11 of 12 domains but was significant only for mood. Although mRS was associated with stroke severity, QOL was independent of both. Seventy-seven percent of survivors of AIS who received IAT reported good QOL. Furthermore, these data suggest that SS-QOL is an independent outcome from stroke severity and disability status.