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Key Points Induction of Sbds deficiency in recipient BM niche cells impairs efficient engraftment of healthy donor HSC after transplantation.SBDS deficiency impairs multiple cellular signaling pathways in post-myeloablation marrow niches critical for restoration of hematopoiesis., Visual Abstract, Bone marrow (BM) niche-derived signals are critical for facilitating engraftment after hematopoietic stem cell (HSC) transplantation (HSCT). HSCT is required for restoration of hematopoiesis in patients with inherited BM failure syndromes (iBMFSs). Shwachman-Diamond syndrome (SDS) is a rare iBMFS associated with mutations in SBDS. Previous studies have demonstrated that SBDS deficiency in osteolineage niche cells causes BM dysfunction that promotes leukemia development. However, it is unknown whether BM niche defects caused by SBDS deficiency also impair efficient engraftment of healthy donor HSC after HSCT, a hypothesis that could explain morbidity noted after clinical HSCT for patients with SDS. Here, we report a mouse model with inducible Sbds deletion in hematopoietic and osteolineage cells. Primary and secondary BM transplantation (BMT) studies demonstrated that SBDS deficiency within BM niches caused poor donor hematopoietic recovery and specifically poor HSC engraftment after myeloablative BMT. We have also identified multiple molecular and cellular defects within niche populations that are driven by SBDS deficiency and are accentuated by or develop specifically after myeloablative conditioning. These abnormalities include altered frequencies of multiple niche cell subsets, including mesenchymal lineage cells, macrophages, and endothelial cells; disruption of growth factor signaling, chemokine pathway activation, and adhesion molecule expression; and p53 pathway activation and signals involved in cell cycle arrest. Taken together, this study demonstrates that SBDS deficiency profoundly impacts recipient hematopoietic niche function in the setting of HSCT, suggesting that novel therapeutic strategies targeting host niches could improve clinical HSCT outcomes for patients with SDS.

This study aimed to identify patient and appointment characteristics associated with no-shows to new patient appointments at a US academic ophthalmology department.Cross-sectional study.This was a study of all adult patients with new patient appointments scheduled with an attending ophthalmologist at Penn State Eye Center between January 1Of 4,628 patients, 759 (16.4%) were no-shows. From the multiple logistic regression model, characteristics associated with no-shows were age (Odds Ratio (OR) for 18-40 years vs.60 years: 3.41, 95% Confidence Interval (CI) 2.57, 4.51, p0.001 and OR for 41-60 years vs.60 years: 2.14, 95% CI 1.67, 2.74, p0.001), median household income (OR for$35,667 vs.$59,445: 1.59, 95% CI 1.08, 2.34, p0.001), insurance (OR for None vs. Medicare: 6.92, 95% CI 4.41, 10.86, p0.001 and OR for Medicaid vs. Medicare: 1.54, 95% CI 1.18, 2.01, p=0.002), race (OR for Black vs. White: 2.62, 95% CI 2.00, 3.43, p0.001 and OR for Other vs. White: 2.02, 95% CI 1.58, 2.59, p0.001), and commute distance (OR for 5-10 mi vs. ≤5 mi: 1.73, 95% CI 1.17, 2.55, p=0.006). Appointments with longer lead times and scheduled with glaucoma or retina specialists were also significantly associated with greater no-shows.Certain patient and appointment characteristics were associated with no-show status. These findings may assist in the development of targeted interventions at the patient, practice, and health system levels to improve appointment attendance.

Purpose The aim of this article is to investigate the impact of a 1-minute video describing resident training with a cataract surgical simulator on patients' perceptions regarding resident involvement in cataract surgery and to identify factors associated with patient willingness to have cataract surgery performed by a resident. Design Cross-sectional survey. Methods An anonymous Likert-style survey was conducted among 430 consecutive adult patients who presented for eye examination at the Penn State Health Eye Center. The survey included questions regarding demographics, understanding of the medical training hierarchy, and patient willingness to have a resident perform their cataract surgery. There were six questions regarding patient willingness to have residents perform their cataract surgery and the second question in this set informs the patient that residents are supervised by an experienced cataract surgeon. Patients were randomly assigned to one of two groups: patients in Group 1 completed the survey only, while patients in Group 2 watched a 1-minute video describing resident training with a cataract surgical simulator prior to completing the survey. Results Four hundred fourteen of the 430 patients (96.3%) completed the survey. Overall, 24.7% (n = 102) of respondents expressed willingness to allow an ophthalmology resident to perform their cataract surgery, and that proportion increased to 54.0% (n = 223) if the patient was informed that the resident would be supervised by an experienced cataract surgeon. Patients in Group 2 were twice as likely compared with patients in Group 1 to express willingness to allow an ophthalmology resident to perform their cataract surgery (odds ratio 1.92 [1.18–3.11], p = 0.009). Conclusions A thorough informed consent process including information regarding attending supervision and a brief video detailing resident training with a cataract surgery simulator may increase patient willingness to allow resident participation in cataract surgery.

Interventions have modest impact on reducing excessive gestational weight gain (GWG) in pregnant women with overweight/obesity. This two-arm feasibility randomized control trial tested delivery of and compliance with an intervention using adapted dosages to regulate GWG, and examined pre-post change in GWG and secondary outcomes (physical activity: PA, energy intake: EI, theories of planned behavior/self-regulation constructs) compared to a usual care group. Pregnant women with overweight/obesity (N = 31) were randomized to a usual care control group or usual care + intervention group from 8 to 2 weeks gestation and completed the intervention through 36 weeks gestation. Intervention women received weekly evidence-based education/counseling (e.g., GWG, PA, EI) delivered by a registered dietitian in a 60-min face-to-face session. GWG was monitored weekly; women within weight goals continued with education while women exceeding goals received more intensive dosages (e.g., additional hands-on EI/PA sessions). All participants used mHealth tools to complete daily measures of weight (Wi-Fi scale) and PA (activity monitor), weekly evaluation of diet quality (MyFitnessPal app), and weekly/monthly online surveys of motivational determinants/self-regulation. Daily EI was estimated with a validated back-calculation method as a function of maternal weight, PA, and resting metabolic rate. Sixty-five percent of eligible women were randomized; study completion was 87%; 10% partially completed the study and drop-out was 3%. Compliance with using the mHealth tools for intensive data collection ranged from 77 to 97%; intervention women attended > 90% education/counseling sessions, and 68–93% dosage step-up sessions. The intervention group (6.9 kg) had 21% lower GWG than controls (8.8 kg) although this difference was not significant. Exploratory analyses also showed the intervention group had significantly lower EI kcals at post-intervention than controls. A theoretical, adaptive intervention with varied dosages to regulate GWG is feasible to deliver to pregnant women with overweight/obesity.

OBJECTIVE To evaluate the role of appendectomy in surgical excision of endometriosis and to assess complications associated with appendectomy. METHODS Retrospective study of women undergoing appendectomy for pelvic pain and/or endometriosis during a primary gynecologic procedure. RESULTS Record review was performed for 609 women who underwent appendectomy between 2013 and 2019 for pelvic pain (6.9%, 42/609), stage I-II endometriosis (63.7%, 388/609), or stage III-IV endometriosis (29.4%, 179/609). Appendiceal endometriosis (AppE) was present in 14.9% (91/609); 2.4% without endometriosis (1/42, reference group), 7.0% with stage I-II endometriosis (27/388, odds ratio [OR] 3.06, 95% confidence interval [CI] 0.41-23.11, P = 0.278), and 35.2% with stage III-IV endometriosis (63/179, OR 22.24, 95% CI 2.99-165.40, P = 0.002). AppE was significantly associated with endometriosis present in other locations (OR 5.27, 95% CI 2.66-10.43, P

STUDY OBJECTIVE To evaluate the diagnosis of appendiceal endometriosis (AppE) in coincidental appendectomy specimens using standard versus modified histopathologic analysis. DESIGN Prospective analysis of 300 consecutive patients undergoing coincidental appendectomy at the time of a primary gynecologic procedure. SETTING Academic tertiary referral hospital in the northeastern United States. PATIENTS Women aged 22 to 52 years undergoing gynecologic surgery for the management of endometriosis or chronic pelvic pain between 2013 and 2015. INTERVENTIONS Each appendix specimen underwent standard pathologic analysis with 4 sections performed. Modified pathologic analysis, consisting of standard analysis plus serial sectioning and complete evaluation of the appendix and mesoappendix, was then performed. The first pathologist reviewed all the slides to render a diagnosis. The slides of the subjects with abnormal pathology were rereviewed. On rereview, the diagnosis was confirmed, and the data on which protocol, standard or modified, achieved the diagnosis was rendered. The pathologist performing the second review was blinded to whether the slides from the standard or modified histopathology protocol achieved the original diagnosis. This allowed each specimen to serve as its own control. MEASUREMENTS AND MAIN RESULTS The primary outcome is the detection of AppE. The standard analysis identified endometriosis in 7.7% (n = 23) of appendiceal specimens, whereas the modified analysis identified endometriosis in 10.0% (n = 30; odds ratio 1.3; confidence interval, 1.1-1.7; p = .01). When all pathology findings were combined, the standard analysis identified abnormal pathology in 9.3% (n = 28) of the specimens, whereas the modified analysis identified abnormal pathology in 12.3% (n = 37; odds ratio 1.4; confidence interval, 1.1-1.7; p

Objective To examine the effects of common treatments for polycystic ovary syndrome (PCOS) on a panel of hormones (reproductive/metabolic). Design Secondary analysis of blood from a randomized controlled trial of three 16-week preconception interventions designed to improve PCOS-related abnormalities: continuous oral contraceptive pills (OCPs, N = 34 subjects), intensive lifestyle modification (Lifestyle, N = 31), or a combination of both (Combined, N = 29). Materials and Methods Post-treatment levels of activin A and B, inhibin B, and follistatin (FST), as well as Insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 2 (IGFBP-2), glucagon, glucagon-like peptide 1 (GLP-1) and 2, and oxyntomodulin were compared to baseline, and the change from baseline in these parameters were correlated with outcomes. Results Oral contraceptive pill use was associated with a significant suppression in activin A, inhibin A, and anti-mullerian hormone (AMH), but a significant increase in FST. IGF-1, IGFBP-2, glucagon, and GLP-2 levels were significantly decreased. Oxyntomodulin was profoundly suppressed by OCPs (ratio of geometric means: 0.09, 95% confidence interval [CI]: 0.05, 0.18, P Conclusions In women with PCOS, OCPs (and not Lifestyle) affect a wide variety of reproductive/metabolic hormones, but their treatment response does not correlate with live birth.

Objective To assess if a surgical boot camp improves laparoscopic skill among reproduction endocrinology and infertility (REI) fellows and increases fellow desire to incorporate surgical skills into practice and to examine whether fellowship in vitro fertilization (IVF) volume correlates with surgical efficiency. Design Prospective evaluation. Setting Simulation Center. Patient(s) Forty REI fellows. Intervention(s) Fellows were timed before and after training in laparoscopic suturing and knot tying and while using virtual simulators. Fellows were surveyed before boot camp on prior experience with IVF and reproductive surgery, and immediately and 1 month after boot camp on their desire to incorporate surgical skills into practice. Main Outcome Measure(s) Efficiency of laparoscopic suturing and knot tying before and after boot camp; likelihood and persistence of incorporating surgical skills into practice immediately and 1 month after boot camp; and correlation between fellowship IVF volume and fellow surgical efficiency. Result(s) Fellows experienced significant improvement in laparoscopic suturing (44 sec), intracorporeal knot tying (82 sec), and extracorporeal knot tying (71 sec). Fellows reported being more likely to incorporate operative hysteroscopy (89%), operative laparoscopy (87%), and laparoscopic suturing (84%) into practice immediately following boot camp with no difference 1 month later. Fifty-four percent of fellows reported being more likely to perform robotic surgery after the boot camp, increasing to 70% 1 month later. There were weak correlations between IVF case volume and efficiency in laparoscopic suturing or hysteroscopic polypectomy (Spearman correlation coefficients, -0.14 and -0.03). Conclusion(s) An intensive surgical boot camp enhances surgical skill among REI fellows.

Objective: The aim of this study was to determine the influence of immediate preoperative gabapentin on postoperative pain in patients undergoing laparoscopy for benign gynecologic indications. Mat...

Dwyer (lateral calcaneal closing wedge) osteotomy is commonly used in surgical correction of heel varus deformity. The purpose of this study was to determine the effect of wedge size and angle of osteotomy on deformity correction using preoperative imaging analysis with three-dimensional (3D) printed modeling. Seven patients diagnosed with pes cavovarus deformity who underwent Dwyer calcaneal osteotomy were identified retrospectively. Preoperative computed tomogrphy scans were used to create 3D printed models of the foot. After18 variations of osteotomy and fixation performed for each foot, Harris heel and Saltzman images were obtained. The angle between the tibia-talus axis and calcaneal-tuber axis was measured and compared to pre-osteotomy state. Change in the calcaneal lengths was also analyzed. The average degree correction of deformity per mm of bone resected was 3.8 ± 0.2 degrees in the Harris Heel view and 2.7 ± 0.8 degrees in the Saltzman view. A significant increase in correction was obtained with 10 mm compared with 5 mm wide wedges (P < .001). The difference in correction was not statistically significant between 30 and 45 degree cuts or osteotomy distance from the posterior calcaneal tuberosity, but a 45 degree sagittal angle resulted in less calcaneal shortening compared to 30 degrees (P = .02). A clinically driven method using patient-specific 3D models for determining effects of calcaneal osteotomy variables in correcting hindfoot alignment was developed. In summary, the amount of wedge resected impacts hindfoot alignment more than location and sagittal angle of the cut. Calcaneal shortening depends on sagittal angle of the cut.

Background: Optimal modalities for pain control in shoulder arthroplasty are not yet established. Although regional nerve blockade has been a well-accepted modality, complications and rebound pain have led some surgeons to seek other pain control modalities. Local injection of anesthetics has recently gained popularity in joint arthroplasty. The purpose of this study was to evaluate the effectiveness and complication rate of a low-cost local anesthetic injection mixture for use in total shoulder arthroplasty (TSA) compared with interscalene brachial plexus blockade. Methods: A total of 314 patients underwent TSA and were administered general anesthesia with either a local injection mixture (local infiltration anesthesia [LIA], n = 161) or peripheral nerve block (PNB, n = 144). Patient charts were retrospectively reviewed for postoperative pain scores, 24-hour opioid consumption, and 90-day postoperative complications. Results: Immediate postoperative pain scores were not significantly different between groups (P = .94). The LIA group demonstrated a trend toward lower pain scores at 24 hours postoperatively (P = .10). Opioid consumption during the first 24 hours following surgery was significantly reduced in the LIA group compared with the PNB group (P < .0001). There was a trend toward fewer postoperative nerve and cardiopulmonary complications in the LIA group than the PNB group (P = .22 and P = .40, respectively) Conclusion: Periarticular local injection mixtures provide comparable pain control to regional nerve blocks while reducing opioid use and postoperative complications following TSA. Local injection of a multimodal anesthetic solution is a viable option for pain management in TSA.

Uncovering links between processing conditions, microstructure, and properties is a central tenet of materials analysis. It is well known that microstructure determines properties, but expressing these structural features in a universal quantitative fashion has proved to be extremely difficult. Recent efforts have focused on training supervised learning algorithms to place microstructure images into predefined classes, but this approach assumes a level of a priori knowledge that may not always be available. In this paper, we expand this idea to the semi-supervised context in which class labels are known with confidence for only a fraction of the microstructures that represent the material system. It is shown that classifiers which perform well on both the high-confidence labeled data and the unlabeled, ambiguous data can be constructed by relying on the labeling consensus of a collection of semi-supervised learning methods. We also demonstrate the use of novel error estimation approaches for unlabeled data to establish robust confidence bounds on the classification performance over the entire microstructure space.

BACKGROUND Pharmacogenetic studies in asthma cohorts, primarily made up of White people of European descent, have identified loci associated with response to inhaled beta agonists and corticosteroids (ICSs). Differences exist in how individuals from different ancestral backgrounds respond to long-acting beta agonist (LABA) and ICSs. Therefore, we sought to understand the pharmacogenetic mechanisms regulating therapeutic responsiveness in individuals of African descent. METHODS We did ancestry-based pharmacogenetic studies of children (aged 5-11 years) and adolescents and adults (aged 12-69 years) from the Best African Response to Drug (BARD) trials, in which participants with asthma uncontrolled with low-dose ICS (fluticasone propionate 50 μg in children, 100 μg in adolescents and adults) received different step-up combination therapies. The hierarchal composite outcome of pairwise superior responsiveness in BARD was based on asthma exacerbations, a 31-day difference in annualised asthma-control days, or a 5% difference in percentage predicted FEV1. We did whole-genome admixture mapping of 15 159 ancestral segments within 312 independent regions, stratified by the two age groups. The two co-primary outcome comparisons were the step up from low-dose ICS to the quintuple dose of ICS (5 × ICS: 250 μg twice daily in children and 500 μg twice daily in adolescents and adults) versus double dose (2-2·5 × ICS: 100 μg twice daily in children, 250 μg twice daily in adolescents and adults), and 5 × ICS versus 100 μg fluticasone plus a LABA (salmeterol 50 μg twice daily). We used a genome-wide significance threshold of p

The aim of this systematic review with meta-analysis was to evaluate the effect on length of labor when patients receive IVF with or without dextrose. Searches were performed in electronic databases from inception of each database to May 2018. Trials comparing intrapartum IVF containing dextrose (i.e. intervention group) with no dextrose or placebo (i.e. control group) were included. Only trials examining low-risk pregnancies in labor at ≥36 weeks were included. Studies were included regardless of oral intake restriction. The primary outcome was the length of total labor from randomization to delivery. The meta-analysis was performed using the random effects model. Sixteen trials (n = 2503 participants) were included in the meta-analysis. Women randomized in the IVF dextrose group did not have a statistically significant different length of total labor from randomization to delivery compared to IVF without dextrose (MD −38.33 min, 95% CI −88.23 to 11.57). IVF with dextrose decreased the length of the first stage (MD −75.81 min, 95% CI −120.67 to −30.95), but there was no change in the second stage. In summary, use of IVF with dextrose during labor in low-risk women at term does not affect total length of labor, but it does shorten the first stage of labor.

Introduction: Overprescribing by providers is a leading contributor to the opioid crisis. Despite available information regarding the role that physician prescribing plays in the community availability of opioids, guidelines for the management of acute pain remain sparse. This project aims to evaluate opioid prescribing, opioid usage patterns, and postoperative pain control in patients undergoing isolated mid-urethral sling (MUS) placement. Methods: Patients who underwent isolated MUS placement from March 19, 2019 through March 19, 2020 were contacted by telephone in May 2020 and asked a series of questions examining opioid usage, postoperative pain, what they did with unused opioids, and whether they had received education on disposal techniques. A chart review was utilized to determine the amount of opioid prescribed, the presence of any operative complications, and medical and demographic characteristics of subjects. Results: A total of 53 subjects met inclusion criteria, of which 31 participated in a phone interview. Of the 53 subjects, 54.7% received a postoperative opioid prescription, and all but two of these subjects filled their prescription. Of the interviewed subjects, only 66.6% who filled a prescription reported using opioids Fifty percent (n=6) of patients that required oxycodone reported use of four tablets (30 morphine milligram equivalents (MMEs)) or less and used for 1-2 days postoperatively. No patient reported using opioids beyond five days. Only 22.2% reported receiving instruction on opioid disposal, and 16.7% returned unused opioids to a disposal center. 87.1% of subjects rated postoperative pain as “better” or “much better” than expected. Conclusion: Patients undergoing isolated MUS placement require limited amounts of postoperative opioids, if any are needed at all, to achieve satisfactory pain control. Excess prescribed opioids, along with inadequate patient education on proper disposal techniques, may contribute towards opioids that are at risk of diversion for nonmedical use.

Parkinson's disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. Clinical findings indicate that LID typically only occurs following the progression of PD motor symptoms from the unilateral (Hoehn and Yahr (HY) Stage I) to the bilateral stage (HY Stage II). This suggests the presence of some compensatory interhemispheric mechanisms that delay the occurrence of LID. We therefore investigated the role of interhemispheric connections of the nigrostriatal pathway on LID expression in a rat model of PD. The striatum of one hemisphere of rats was first injected with a retrograde tracer to label the ipsi- and cross-hemispheric nigrostriatal pathways. Rats were then split into groups and unilaterally lesioned in the striatum or medial forebrain bundle of the tracer-injected hemisphere to induce varying levels of hemiparkinsonism. Finally, rats were treated with levodopa and tested for the expression of LID. Distinct subsets emerged from rats that underwent the same lesioning paradigm based on LID. Strikingly, non-dyskinetic rats had significant sparing of their cross-hemispheric nigrostriatal pathway projecting from the unlesioned hemisphere. In contrast, dyskinetic rats only had a small proportion of this cross-hemispheric nigrostriatal pathway survive lesioning. Crucially, both non-dyskinetic and dyskinetic rats had nearly identical levels of ipsi-hemispheric nigrostriatal pathway survival and parkinsonian motor deficits. Our data suggest that the survival of the cross-hemispheric nigrostriatal pathway plays a crucial role in preventing the expression of LID and represents a potentially novel target to halt the progression of this devastating side-effect of a common anti-PD therapeutic.

Background Admission to the intensive care unit (ICU) after surgery can be associated with significant morbidity and mortality. This observational cohort study aims to identify perioperative factors associated with post-operative ICU admission in patients undergoing elective non-cardiac surgery. Methods Data from the ACS NSQIP® database at a tertiary care academic medical center were analyzed from January 2011 to September 2016. Univariable and multivariable logistic regression of patient and surgery-specific characteristics was performed to assess association with post-operative ICU admission. The Current Procedural Terminology (CPT) and International Classification of Diseases (ICD-9) billing codes, as well as associated outcomes, were reviewed. Results Of 5254 database patient records, 1150 met our inclusion criteria. Elevated body mass index (BMI), longer procedure duration and a diagnosis of disseminated cancer were associated with post-operative ICU admission. Prostatectomy and morbid obesity were the most common CPT and ICD-9 codes identified. Patients who were admitted to the ICU after surgery had a longer hospital length of stay (LOS), had a higher frequency of readmission, re-operation, and in-hospital mortality. Conclusion Admission to the ICU after elective non-cardiac surgery is common. Our analysis of the ACS NSQIP® database identified elevated BMI, longer duration of surgery and disseminated cancer as predictors of post-operative ICU admissions in patients undergoing elective non-cardiac surgery.

Rapid-eye-movement (REM) sleep without atonia (RSWA), a marker of REM sleep behavior disorder (RBD), is frequently comorbid with Parkinson’s disease (PD). Although rodent models are commonly used for studying PD, the neurobiological and behavioral correlates of RBD remain poorly understood. Therefore, we developed a behavior-based criteria to identify RSWA in the hemiparkinsonian rat model of PD. Video recordings of rats were analyzed, to develop a criteria consisting of behavioral signs that occurred during polysomnographically confirmed epochs of sleep-wake stages. The sleep-slouch, a postural shift of the body or head caused only by gravity, was identified as a unique behavioral sign of REM sleep onset and was altered in hemiparkinsonian rats during RSWA. There was a significant correlation between the behavior-based criteria and polysomnograms for all sleep-wake stages in control but not hemiparkinsonian rats indicating a deterioration of sleep-wake architecture in parkinsonism. We then tested the efficacy of levodopa in ameliorating RSWA using intermittent and around-the-clock (ATC) dosing regimens. ATC levodopa dosing at 4 mg/kg for 48 h caused a significant reduction of RSWA as measured by polysomnography and the behavioral-based criteria along with an amelioration of forelimb motor deficits. Our findings show that the phenomenological correlates of RSWA can be reliably characterized in the hemiparkinsonian rat model. ATC levodopa administration ameliorates RSWA in this model without deleterious consequences to the overall sleep-wake architecture and therapeutic benefits for parkinsonian motor deficits. These findings suggest that further study may allow for the application of a similar approach to treat RBD in PD patients.

Quetiapine, an atypical antipsychotic medication has lacked pre-clinical validation for its purported benefits in the treatment of delirium. This laboratory investigation examined the effects of quetiapine on the attentional set shifting task (ASST), a measure of cognitive flexibility and executive functioning, in a rodent model of lipopolysaccharide (LPS) mediated neuroinflammation. 19 Sprague Dawley female rats were randomly selected to receive intraperitoneal placebo (N = 5), LPS and placebo (N = 7) or LPS and quetiapine (n = 7) and performed the ASST. We measured trials to criterion, errors, non-locomotion episodes and latency to criterion, serum cortisol and tumor necrosis factor alpha (TNF-α) levels. TNF-α levels were not different between groups at 24 h. Cortisol levels in the LPS + Quetiapine group were reduced compared to LPS + Placebo (P 0.0167). We demonstrated preserved reversal learning, no effect on attentional set shifting and normalized cortisol levels in quetiapine-treated rats in this neuroinflammatory model of delirium. This suggests that quetiapine’s beneficial effects in delirium may be related to the preservation of reversal learning and potential downstream effects related to reduction in cortisol production.

In 2017, we surveyed long-term care facilities in Pennsylvania regarding antimicrobial stewardship and infection prevention and control (IPC) practices. Among 244 responding facilities, 93% had IPC programs and 47% had antimicrobial stewardship programs. There was significant variation in practices across facilities, and a number of program implementation challenges were identified.

Weibin Shi,1,2 Renuka Rudra,1,2 To-Nhu Vu,3 Yuri Gordin,1,2 Ryan Smith,1,2 Allen R Kunselman4 1Department of Physical Medicine and Rehabilitation, Penn State Health Milton S Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA; 2Penn State Hershey Rehabilitation Hospital, Hummelstown, PA, USA; 3Department of Anesthesiology & Perioperative Medicine, Penn State Health Milton S Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA; 4Department of Public Health Sciences, Penn State Hershey College of Medicine, Hershey, PA, USACorrespondence: Weibin Shi; To-Nhu Vu Email wshi@pennstatehealth.psu.edu; tonhuvu@pennstatehealth.psu.eduBackground: Sensory stimulation threshold (SST) has been used as a surrogate marker to target a nerve branch for radiofrequency (RF) denervation; however, the validity of SST as a prognostic marker is still under debate.Objective: To assess whether lower SST values correlate with better outcomes of radiofrequency denervation for facetogenic low back pain.Design: Prospective cohort study.Patients: Sixty-seven patients who underwent radiofrequency denervation for low back pain.Methods: Correlations, between the average percentage of pain relief from diagnostic medial branch block (MBB) and RF denervation procedure outcome, and between SST and RF denervation procedure outcome, were analyzed using Spearman correlation coefficient (rs). Wilcoxon rank sum test was performed to assess whether magnitude and duration of pain relief following RF denervation differed by the levels of SST (< 0.5 and ≥ 0.5) or pain relief (< 80% and ≥ 80%) from diagnostic MBB.Results: There was a positive correlation between pain relief after diagnostic MBB and pain relief 2 weeks after denervation (rs 0.31, 95% CI 0.08 to 0.51, p < 0.01), but not between pain relief after MBB and pain relief 6 months after denervation, nor pain relief duration after denervation. There was a negative correlation between SST and pain relief 6 months after denervation (rs − 0.41, 95% CI − 0.59 to − 0.18, p < 0.001). There was also a negative correlation between SST and pain relief duration after denervation (rs − 0.33, 95% CI − 0.53 to − 0.09, p < 0.01).Conclusion: SST is a viable measurement with which to guide needle placement during RF denervation for lumbar facet pain, and enhances pain relief outcomes.Keywords: sensory stimulation threshold, radiofrequency ablation, lower back pain, lumbar facet arthropathy, outcome

Background: Psychiatric disorders, including anxiety and depression, are significantly more common in patients with inflammatory bowel disease (IBD). We established an integrated psychiatry clinic for IBD patients at our tertiary center IBD clinic to provide patients with critical, but frequently unavailable, coordinated mental health services. We undertook this study to evaluate the impact of this service on psychiatric outcomes, quality of life, and symptom experience. Methods: We performed a longitudinal prospective study comparing patients who had been cared for at our integrated IBD-psychiatry clinic to those who had not. We abstracted demographic and clinical information as well as contemporaneous responses to validated surveys. Results: Thirty-six patients cared for in the IBD psychiatry clinic were compared to a control cohort of 35 IBD patients. There was a significant reduction in the Hospital Anxiety and Depression Scale (HADS) depression score over time in the study cohort (p = 0.001), though not in the HADS anxiety score. When compared to the control group, the study cohort showed a significant reduction in the HADS depression score. No significant differences were observed in the Harvey-Bradshaw Index, Simple Clinical Colitis Activity Index, or Short IBD Questionnaire. Conclusions: This is the first study to evaluate the impact of an integrated psychiatry clinic for IBD patients. Unlike their control counterparts, individuals treated in this clinic had a significant reduction in the mean HADS depression score. Larger scale studies are necessary to verify these findings. However, this study suggests that use of an integrated psychiatry IBD clinic model can result in improvement in mental health outcomes, even in the absence of significant changes in IBD activity.

To determine whether an inpatient post-cesarean analgesic regimen which separated oxycodone and acetaminophen resulted in less inpatient opioid use, when compared to a regimen using combination medications containing both acetaminophen and oxycodone in a cohort including patients of all gestational ages, acuity levels, and modes of operative anesthesia.This is a retrospective cohort study which was conducted at a single tertiary care center Labor and Delivery unit. Data were collectedThe primary outcome was inpatient opioid medication use per 12-h period in intravenous morphine mg equivalents (MME). Patients received an average of 4.6 ± 3.5 MME IV morphine per 12 h in the Separate Medication group and 5.7 ± 3.7 MME IV morphine per 12 h in the Combined Medication group. When controlled for several covariates, the Separate Medication group took significantly fewer MME per 12-h period (mean difference = -1.2, 95% CI: (-2.3, -0.1),An analgesic regimen where oxycodone is ordered separately from acetaminophen is associated with reduced inpatient opioid medication use in patients of all gestational ages, acuity levels, and modes of operative anesthesia.

Background Lisfranc ligamentous injuries are complex, and their treatment, along with the preferred method of fixation, is controversial. Implementing a flexible synthetic augmentation device (fibertape) has been described as an alternative to traditional screw fixation. This biomechanical study evaluated two fibertape devices with interference screw fixation: InternalBrace, and InternalBrace with supplementary intercuneiform stabilization. Methods The diastasis and relative angular displacement between bones were measured at three midfoot joints in the Lisfranc articulation. Measurements were obtained for the pre-injured, injured, and post-fixation stages under static loading. Specimens then underwent stepwise increases in cyclic loading performed at 1 Hz and 100 cycles, at 100 N ground reaction force intervals from 500 to 1200 N to simulate postoperative loading, and then up to 1800 N to simulate high loads. Failure of fixation was defined as diastasis greater than 2 millimeters at the second-metatarsal – medial-cuneiform joint. Results InternalBrace specimens demonstrated failures in 3 of 9 (33%) specimens at cyclic loads of 1000 N. Conversely, InternalBrace with Supplementary Limb specimens had 1 failure at 1200 N. The difference in diastasis at the second metatarsal-medial cuneiform joint was statistically significant between the two groups at higher loads of 1600N (p = 0.019) and 1800N (p = 0.029). Conclusion The use of InternalBrace for ligamentous Lisfranc injuries appears to provide a biomechanically viable alternative for withstanding early postoperative protected weight bearing. Furthermore, the use of a supplementary limb in addition to the InternalBrace fibertape fixation method appears to enhance its biomechanical efficacy.

Category: Trauma; Basic Sciences/Biologics; Midfoot/Forefoot; Sports Introduction/Purpose: Lisfranc ligamentous injuries are complex. Controversy exists regarding their treatment and preferred method of fixation. Fixation methods employing a FiberTape device and interference screw fixation have been described as an alternative to traditional screw fixation. The purpose of this biomechanical study was to evaluate two methods of fixation utilizing interference screw fixation with FiberTape augmentation in a cadaveric model. Methods: 9 paired cadaveric feet (mid tibia/fibula) were separated into two groups based on fixation method: FiberTape alone and FiberTape with supplementary limb into the middle cuneiform via anchor. At three joints of the midfoot (second metatarsal - medial cuneiform, intermediate cuneiform - medial cuneiform, second metatarsal - intermediate cuneiform), the diastasis and relative angular displacement between bones in the coronal plane were measured for static and cyclic loading. Measurements were obtained for the native (pre-injured), injured, and post-fixation in static loading. Fixed specimens then underwent stepwise increases in cyclic loading performed at 1 Hz and 100 cycles, at 100 N intervals from 500 to 1800 N ground reaction force. The Achilles tendon was also loaded to simulate postoperative weightbearing. Failure of fixation was defined as diastasis at the second metatarsal - medial cuneiform joint greater than 2 millimeters. Results: FiberTape specimens demonstrated diastasis failures of 3 of 9 (33%) specimens at cyclic loads of 1000 N. Conversely, FiberTape with supplementary limb specimens all survived past this loading magnitude, with 1 failing at supraphysiologic loads (>1200 N). The difference in diastasis at the second metatarsal-medial cuneiform joint was statistically significant between the two groups at forces of 1600N (p = 0.019) and 1800N (p = 0.029). There were no significant differences between the other joint diastases and relative angular displacements. Conclusion: The use of FiberTape for fixation of ligamentous Lisfranc injuries appears to provide a biomechanically viable alternative for withstanding early post-operative protected weightbearing. Furthermore, the use of a supplementary limb in addition to the FiberTape fixation method appears to enhance its biomechanical efficacy under cyclic loading especially at higher loads.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.

Introduction:corneal transplantation is a surgical procedure requiring consistent long-term follow-up to maximize the chance of graft survival. The purpose of this study was to explore patient characteristics and reasons for being lost to follow-up (LTFU). Methods:a retrospective review of clinical records from January 2012 to October 2014 was conducted of patients who received corneal transplantation at Tenwek Hospital. At the time of chart review, all patients who provided a mobile phone number were contacted to answer a phone questionnaire. Logistic regression was used to assess the association of each patient characteristic, separately, with the outcome of LTFU. Results:of the 118 patients that met inclusion criteria, 40 (33.9%) were considered LTFU by failing to follow up at Tenwek Hospital to at least one year postoperatively. The odds of LTFU for patients age 60 and older were 3.78 times that of those who were 18-59 (95% CI: 1.21-11.80]; p-value=0.02). The odds of LTFU for patients with a preoperative diagnosis of pseudophakic bullous keratopathy were 3.83 times that of those with a preoperative diagnosis of keratoconus (95% CI: [1.13-12.94]; p-value=0.03). Education level, employment status, distance from the hospital, and possession of a mobile contact number appeared marginally associated with follow-up status, though not statistically significant at the 0.05 significance level. Financial barriers were the most commonly cited reason for LTFU (42.4%, n=14). Conclusion:certain reasons and patient characteristics may be associated with follow-up adherence. Identifying these factors may help providers identify patients who are at a higher risk of LTFU and influence providers in medical decision-making and system-based interventions when offering corneal transplantation.

Successful tibiotalar joint fusion relies on adequate compression. Compression following joint preparation may be affected by the extent to which the fibula holds the joint out to anatomical length. The purpose of this study was to evaluate the effect of various distal fibula osteotomies on tibiotalar joint compression.Eight adult cadaveric lower extremity specimens with an intact ankle joint and syndesmotic complex were evaluated. The ankle joint cartilage was denuded to subchondral bone. The fibula was surgically modified with three progressing procedures including an oblique fibula osteotomy, 1 cm resection, and distal fibula resection. A transducer was utilized to measure tibiotalar joint force, contact area, and peak pressure values while compressive forces of 30 N, 50 N, and 100 N were applied to the proximal tibia/fibula.Distal fibula resection significantly increased tibiotalar joint force, contact area, and peak pressure the most of all fibula conditions tested compared to intact fibula control (p .05). Tibiotalar joint force and peak pressures were significantly increased with a distal fibula oblique osteotomy, 1 cm resection, and complete resection under both 30 and 50 N applied compressive force (p .05).Complete distal fibular resection results in higher tibiotalar joint force, contact area, and peak pressure which may improve clinical rates of successful ankle fusion.

The purpose of this study was to evaluate the hemodynamic properties and microemboli capture associated with different vacuum-assisted venous drainage (VAVD) vacuum levels and venous reservoir levels in a neonatal cardiopulmonary bypass circuit. Trials were conducted in 2 parallel circuits to compare the performance of Capiox Baby RX05 oxygenator with separate AF02 arterial filter to Capiox FX05 oxygenator with integrated arterial filter. Arterial cannula flow rate to the patient was held at 500 mL/min and temperature maintained at 32°C, while VAVD vacuum levels (0 mm Hg, -15 mm Hg, -30 mm Hg, -45 mm Hg, -60 mm Hg) and venous reservoir levels (50 mL, 200 mL) were evaluated in both oxygenators. Hemodynamic parameters measuring flow, pressure, and total hemodynamic energy were made in real time using a custom-made data acquisition system and Labview software. Nearly 10 cc bolus of air was injected into the venous line and gaseous microemboli detected using an Emboli Detection and Classification Quantifier. Diverted blood flow via the arterial filter's purge line and mean pressures increased with increasing VAVD levels (P < 0.01). Mean pressures were lower with lower venous reservoir levels and were greater in RX05 groups compared to FX05 (P < 0.01). Microemboli detected at the preoxygenator site increased with higher VAVD vacuum levels and lower venous reservoir levels (P < 0.01). The amount of microemboli captured by the FX05 oxygenator with integrated arterial filter was greater than by the RX05 oxygenator alone, although both oxygenators were able to clear microemboli before reaching the pseudo-patient.

To compare surgical excision and ablation of endometriosis for treatment of chronic pelvic pain.Randomized clinical trial with 12-month follow-up (Canadian Task Force classification I).Single academic tertiary care hospital.Women with minimal to mild endometriosis undergoing laparoscopy.Excision or ablation of superficial endometriosis at the time of robot-assisted laparoscopy.Primary outcome was visual analog scale (VAS) scoring at baseline and 6 and 12 months for menstrual pain, nonmenstrual pain, dyspareunia, and dyschezia. Secondary outcomes included survey results at baseline and 6 and 12 months from the Short Form Health Survey, Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire, and the International Pelvic Pain Assessment. From December 2013 to October 2014, 73 patients were randomized intraoperatively to excision (n = 37) or ablation (n = 36) of endometriosis. Patients were followed at 6 and 12 months to evaluate the above outcomes. After ablation of endometriosis, dyspareunia (VAS scores) improved at 6 months (mean change [MC], -14.07; 95% confidence interval [CI], -25.93 to -2.21; p = .02), but improvement was not maintained at 12 months. Dysmenorrhea improved at 6 months (MC, -26.99; 95% CI, -41.48 to -12.50; p .001) and 12 months (MC, -24.15; 95% CI, 39.62 to -8.68; p = .003) with ablation. No significant changes were seen in VAS scores after excision at 6 or 12 months. When comparing ablation and excision, the only significant difference was a change in dyspareunia at 6 months (MC, -22.96; 95% CI, -39.06 to -6.86; p = .01).Treatment with ablation improved dysmenorrhea at 6 and 12 months and improved dyspareunia at 6 months as compared with preoperative data. However, only dyspareunia demonstrated a significant difference between ablation and excision. Excision and ablation showed similar effectiveness for the treatment of pain associated with superficial endometriosis, with ablation showing more significant individual changes. Careful patient counseling regarding expectations of surgical intervention is vital in the management of endometriosis.

Objective To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. Design Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. Setting Two academic medical centers. Patients Women with PCOS (N = 114) defined by the Rotterdam criteria. Interventions Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. Main Outcome Measures Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale−Revised (FSDS-R) scores after 16 weeks. Results There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. Conclusion(s) Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. Clinical Trial Registration Number NCT00704912.

Objective To investigate the relationship between maximal placental thickness during routine anatomy scan and birthweight at delivery. Methods This retrospective descriptive study analyzed 200 term, singleton deliveries in 2016 at Penn State Hershey Medical Center. We measured maximal placental thickness in the sagittal plane from the ultrasound images of the placenta obtained at the 18–21-week fetal anatomy screen. The relationship between placental thickness and neonatal birthweight was assessed using Pearson’s correlation coefficient (r) with 95% confidence interval (CI). Logistic regression was used to assess the association between placental thickness and secondary binary outcomes of neonatal intensive care unit (NICU) admission and poor Apgar scores. Two-sample t-tests, or exact Wilcoxon rank-sum test for non-normally distributed data, were used to assess for differences attributable to medical comorbidities (pre-gestational diabetes, gestational diabetes, chronic hypertension, gestational hypertension, preeclampsia and eclampsia). Results Placental thickness had a positive correlation with neonatal birthweight [r=0.18, 95% CI=(0.05, 0.32)]. The mean placental thickness measured 34.2±9.7 mm. The strength of the correlation remained similar when adjusting for gestational age (r=0.20) or excluding medical comorbidities (r=0.19). There was no association between placental thickness and NICU admission, Apgar scores Conclusion Our study demonstrated a positive correlation between sonographic placental thickness and birthweight. Future prospective studies are warranted in order to further investigate whether a clinically significant correlation exists while adjusting for more covariates.

The objective of this study is to compare hemodynamic performances under different pulsatile control algorithms between Medos DeltaStream DP3 and i-cor diagonal pumps in simulated pediatric and adult ECLS systems. An additional pilot study was designed to test hemolysis using two pumps during 12h-ECLS. The experimental circuit consisted of parallel combined pediatric and adult ECLS circuits using an i-cor pump head and either an i-cor console or Medos DeltaStream MDC console, a Medos Hilite 2400 LT oxygenator for the pediatric ECLS circuit, and a Medos Hilite 7000 LT oxygenator for the adult ECLS circuit. The circuit was primed with lactated Ringer's solution and human packed red blood cells (hematocrit 40%). Trials were conducted at various flow rates (pediatric circuit: 0.5 and 1L/min; adult circuit: 2 and 4L/min) under nonpulsatile and pulsatile modes (pulsatile amplitude: 1000-5000rpm [1000 rpm increments] for i-cor pump, 500-2500rpm [500 rpm increments] for Medos pump) at 36°C. In an additional protocol, fresh whole blood was used to test hemolysis under nonpulsatile and pulsatile modes using the two pump systems in adult ECLS circuits. Under pulsatile mode, energy equivalent pressures (EEP) were always greater than mean pressures for the two systems. Total hemodynamic energy (THE) and surplus hemodynamic energy (SHE) levels delivered to the patient increased with increasing pulsatile amplitude and decreased with increasing flow rate. The i-cor pump outperformed at low flow rates, but the Medos pump performed superiorly at high flow rates. There was no significant difference between two pumps in percentage of THE loss. The plasma free hemoglobin level was always higher in the Medos DP3 pulsatile group at 4 L/min compared to others. Pulsatile control algorithms of Medos and i-cor consoles had great effects on pulsatility. Although high pulsatile amplitudes delivered higher levels of hemodynamic energy to the patient, the high rotational speeds increased the risk of hemolysis. Use of proper pulsatile amplitude settings and intermittent pulsatile mode are suggested to achieve better pulsatility and decrease the risk of hemolysis. Further optimized pulsatile control algorithms are needed.

Translational research is a useful tool to provide scientific evidence for cannula selection during extracorporeal life support (ECLS). The objective of this study was to evaluate four Avalon Elite bi-caval dual lumen cannulas and nine femoral arterial cannulas in terms of flow range, circuit pressure, pressure drop, and hemodynamic energy transmission in a simulated adult ECLS model. A veno-venous ECLS circuit was used to evaluate four Avalon Elite bi-caval dual lumen cannulas (20, 23, 27, and 31 Fr), and a veno-arterial ECLS circuit was used to evaluate nine femoral arterial cannulas (15, 17, 19, 21, and 23 Fr). The two circuits included a Rotaflow centrifugal pump, a Quadrox-D adult oxygenator, and 3/8 in ID tubing for arterial and venous lines. The circuits were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 40%). Trials were conducted at rotational speeds from 1000 to 5000 RPM (250 rpm increments) for each Avalon cannula, and at different flow rates (0.5-7 L/min) for each femoral arterial cannula. Real-time pressure and flow data were recorded for analysis. Small caliber cannulas created higher circuit pressures, higher pressure drops and higher M-numbers compared with large ones. The inflow side of Avalon dual lumen cannula had a significantly higher pressure drop than the outflow side (inflow vs. outflow: 20 Fr-100.2 vs. 49.2 mm Hg at 1.1 L/min, 23 Fr-93.7 vs. 41.4 mm Hg at 1.6 L/min, 27 Fr-102.3 vs. 42.8 mm Hg at 2.6 L/min, 31 Fr-98.1 vs. 44.7 mm Hg at 3.8 L/min). There was more hemodynamic energy lost in the veno-arterial ECLS circuit using small cannulas compared to larger ones (17 Fr vs. 19 Fr vs. 21 Fr at 4 L/min-Medtronic: 71.0 vs. 64.8 vs. 60.9%; Maquet: 71.4 vs. 65.6 vs. 62.0%). Medtronic femoral arterial cannulas had lower pressure drops (Medtronic vs. Maquet at 4 L/min: 17 Fr-121.7 vs. 125.0 mm Hg, 19 Fr-71.2 vs. 73.7 mm Hg, 21 Fr-42.9 vs. 47.4 mm Hg) and hemodynamic energy losses (Medtronic vs. Maquet at 4 L/min: 17 Fr-43.6 vs. 44.4%, 19 Fr-31.0 vs. 31.4%, 21 Fr-20.8 vs. 22.4%) at high flow rates when compared with the Maquet cannulae. The results for this study provided valuable hemodynamic characteristics of all evaluated adult cannulas with human blood in order to guide ECLS cannula selection in clinical practice. Use of larger cannulas are suggested for VV- and VA-ECLS.

Background: The pathophysiology of adult-acquired flatfoot deformity (AAFD) is not fully explained by degeneration of the posterior tibial tendon alone. While a shortened or dysplastic lateral column has been implicated in flatfoot deformity in pediatrics, there is no study that has quantified the degree of dysplasia in adults with a stage IIb flatfoot deformity, or if any exists at all. Methods: An institutional radiology database was queried for patients with posterior tibial tendon dysfunction (PTTD) who had computed tomography (CT) performed. Controls were patients receiving CT scan for an intra-articular distal tibia fracture without preexisting foot or calcaneal pathology. Clinical notes, physical examination, and weightbearing radiographs were used to find patients that met clinical criteria for stage IIb PTTD. Morphometric measurements of the calcanei were performed involving the length of the calcaneal axis (LCA), height of the anterior process (HAP), and length of the anterior process (LAP). All measurements were performed independently by separate observers, with observers blinded to group assignment. We considered a difference of ±4 mm as our threshold. Results: 7 patients and 7 controls were available for reconstruction and analysis. On average, the LCA was 3.1 mm shorter in patients with stage IIb PTTD compared with controls ( P < .05). The LAP was shorter in PTTD patients compared with controls 3.4 mm ( P < .001). Conclusions: Our results support the hypothesis that the calcaneus of adult patients with stage IIb AAFD is dysplastic when compared with healthy controls, which further supports the utility of lateral column lengthening. Levels of Evidence: Level III: Case-control study

The experimental circuit consisted of an i-cor diagonal pump, a Medos Hilite 800 LT oxygenator, an 8Fr Biomedicus arterial cannula, a 10Fr Biomedicus venous cannula, and six feet of 1/4 in ID tubing for arterial and venous lines. The circuit was primed with lactated Ringer's solution and packed red blood cells (hematocrit 40%). Trials were conducted at various heart rates (90, 120, and 150 bpm) and flow rates (200, 400, and 600mL/min) under nonpulsatile and pulsatile mode with pulsatile amplitudes of 1000-4000rpm (1000 rpm increments). Real-time pressure and flow data were recorded for analysis. The i-cor pump was capable of creating nonpulsatile and electrocardiography (ECG)-synchronized pulsatile flow, and automatically reducing pulsatile frequency by increasing the assist ratio at higher heart rates. Reduced pulsatile frequency led to lower hemodynamic energy generation but did not affect circuit pressure drop. Pulsatile flow delivered more hemodynamic energy to the pseudopatient when compared with nonpulsatile flow. The pump generated more hemodynamic energy with higher pulsatile amplitudes. The i-cor pump can automatically adjust the pulsatile assist ratio to create pulsatile flow at higher heart rates, although this caused some hemodynamic energy loss. Compared with nonpulsatile flow, pulsatile flow generated and transferred more hemodynamic energy to the neonate during ECLS (200-600mL/min), especially at high pulsatile amplitudes and low flow rates.

The objective of this study was to evaluate a pulsatile extracorporeal membrane oxygenation (ECMO) system in terms of hemodynamic energy generation and transmission under various pulsatile amplitudes, flow rates, and pseudopatient pressures in a simulated adult ECMO circuit. Surplus hemodynamic energy (SHE), a measure of the quality of pulsatility, was used to quantify pulsatile flow. The circuit consisted of an i-cor diagonal pump, an adult XLung oxygenator, a 21 Fr Medtronic Biomedicus femoral arterial cannula, a 23/25 Fr Sorin RAP femoral venous cannula, and 3/8 in ID tubing for both arterial and venous lines. The circuit was primed with lactated Ringer's solution and then packed red blood cells (hematocrit 37%). Trials were conducted at 36°C with flow rates of 2-5 L/min (1 L/min increments) under nonpulsatile and pulsatile mode with pulsatile amplitudes of 1000-5000 rpm (1000 rpm increments). The pseudopatient pressure was maintained at 40-100 mm Hg (20 mm Hg increments). Real-time pressure and flow data were recorded for analysis using a custom-made data acquisition system. There was no SHE generated by the pump under nonpulsatile mode. Under pulsatile mode, SHE levels increased with increasing pulsatile amplitude and pseudopatient pressure (P < 0.01) but decreased with increasing flow rate. SHE levels were significantly higher at flow rates of 2-4 L/min. In addition, the XLung oxygenator had acceptable pressure drops (36.1-104.9 mm Hg) and percentages of total hemodynamic energy loss (19.6-43.9%) during all trials. The novel pulsatile ECMO system can create nonpulsatile and pulsatile flow in an adult ECMO model. However, pulsatility gradually weakened with increasing flow rates. Pulsatile amplitude settings were found to have a great impact on pulsatility.

The objective of this study was to assess the hemodynamic properties of the i-cor ECG-synchronized cardiac assist system for off-label use as a short-term cardiac assist device for neonatal and pediatric patients and compare nonpulsatile to pulsatile flow with different amplitudes. The circuit consisted of the i-cor diagonal pump with 3 feet of ¼ inch arterial and venous tubing and a soft-shell reservoir, primed with lactated Ringer's solution and human packed red blood cells (hematocrit 42%). Trials were conducted with three different sets of cannulas (8-Fr arterial 10-Fr venous, 10-Fr arterial 12 Fr-venous, and 12-Fr arterial 14-Fr venous) with increasing flow rates at varying pseudo-patient pressures (40, 60, 80, and 100 mm Hg) and under nonpulsatile mode and pulsatile mode with pulsatile amplitudes 2000, 2500, and 3000 rpm at 36°C. Pressure and flow waveforms were recorded using a custom-made data acquisition device for each trial. Energy equivalent pressure (EEP) was higher than mean pressure under pulsatile mode, and increased with increasing pseudo-patient's pressure and flow rate while EEP was the same as the mean pressure under nonpulsatile mode. Total hemodynamic energy (THE) levels increased with pressure and pulsatile amplitude and slightly decreased with increasing flow rate. The percent THE lost throughout the circuit increased with flow rate and pulsatile amplitude and decreased with pseudo-patient's pressure. SHE levels also increased with pseudo-patient pressure and pulsatile amplitude and decreased with increasing flow rate. The i-cor diagonal pump can be used as a short term cardiac assist device for neonatal and pediatric patients and is able to provide nonpulsatile as well as pulsatile flow. Compared with nonpulsatile flow, pulsatile flow can generate and deliver more hemodynamic energy to the patients.

The objective of this study was to compare the effects of nonpulsatile and ECG-synchronized pulsatile extracorporeal life support on coronary and carotid blood flow velocities using transthoracic echocardiography and vascular ultrasound, respectively. Nine adult swine were randomly separated into nonpulsatile (NP, n = 5) and pulsatile (P, N = 4) groups and placed on ECLS for 24 h using an i-cor ECLS system. Noninvasive transthoracic images of the left and right coronary artery and the left carotid artery were acquired at the pre-ECLS (baseline), 30 min, 3, 6, 9, 12, and 24 h on-ECLS stages. The mean diastolic velocity of the left and right coronary arteries in the NP group significantly decreased after 24 h on ECLS compared to the baseline and 30 min ECLS stages (P < 0.05). There was no statistical difference in the mean diastolic velocity of the coronary arteries in the P group at 30 min, 3-, 6-, 9-, 12-, and 24-h ECLS compared to baseline. The P group showed a smaller decrease in the mean diastolic velocity of coronary arteries between the 30-min ECLS and 3-, 6-, 9-, 13-, 24-h ECLS stages compared to the NP group. The diastolic velocity of the left carotid artery in the NP group significantly decreased during 24-h ECLS compared to the P group (P < 0.05). An ECG-synchronized pulsatile ECLS system appeared to maintain coronary and carotid artery diastolic velocities better than conventional nonpulsatile ECLS. Further investigation of the perfusion modes during ECLS is warranted.

The objective of this study was to evaluate three commercially available ECLS systems with rotary pumps in terms of circuit pressure, pressure drop, perfusion modes, and hemodynamic energy transmission in a simulated adult cardiogenic shock model. One circuit consisted of a Cardiohelp system, which included a Cardiohelp console and HLS Module Advanced 7.0 tubing set with integrated centrifugal pump and oxygenator. The alternative circuit was composed of a Quadrox-D Adult oxygenator connected in series with either an i-cor diagonal pump and console or a Rotaflow centrifugal pump and console. The circuit was primed with lactated Ringer's solution and packed red blood cells (hematocrit 40%). The trials were conducted at flow rates of 1-5 L/min with pseudo patient pressures of 60 mm Hg and 80 mm Hg. Pulsatile flow was tested when using the i-cor system. Mean pre-oxygenator pressure and pressure drop across ECLS circuit (including oxygenator and arterial tubing) were lower when using the Cardiohelp system as compared to the Rotaflow and i-cor systems (P < 0.01). The i-cor system was able to deliver more hemodynamic energy to the pseudo patient because of its ability to produce pulsatile flow (P < 0.01). The Cardiohelp HLS Module Advanced 7.0 integrated oxygenator had a lower resistance than the Quadrox-D oxygenator. Although the compact Cardiohelp system had a better hemodynamic performance when compared to Rotaflow and i-cor systems, the pulsatile flow of the i-cor system delivered more hemodynamic energy to the pseudo patient. This may render more physiological benefits in high-risk patients on ECLS.

BackgroundThe use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown.ObjectivesWe aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects.MethodsWe performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups.ResultsOverall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r=0.33, P&nbsp

The objective was to assess the i-cor electrocardiogram-synchronized diagonal pump in terms of hemodynamic energy properties for off-label use in neonatal and pediatric extracorporeal life support (ECLS) circuits. The neonatal circuit consisted of an i-cor pump and console, a Medos Hilite 800 LT oxygenator, an 8Fr arterial cannula, a 10Fr venous cannula, 91 cm of 0.6-cm ID arterial tubing, and 91 cm of 0.6-cm ID venous tubing. The pediatric circuit was identical except it included a 12Fr arterial cannula, a 14Fr venous cannula, and a Medos Hilite 2400 LT oxygenator. Neonatal trials were conducted at 36°C with hematocrit 40% using varying flow rates (200-600 mL/min, 200 mL increments) and postarterial cannula pressures (40-100 mm Hg, 20 mm Hg increments) under nonpulsatile mode and pulsatile mode with various pulsatile amplitudes (1000-4000 rpm, 1000 rpm increments). Pediatric trials were conducted at different flow rates (800-1600 mL/min, 400 mL/min increments). Mean pressure and energy equivalent pressure increased with increasing postarterial cannula pressure, flow rate, and pulsatile amplitude. Physiologic-like pulsatility was achieved between pulsatile amplitudes of 2000-3000 rpm. Pressure drops were greatest across the arterial cannula. Pulsatile flow generated significantly higher total hemodynamic energy (THE) levels than nonpulsatile flow. THE levels at postarterial cannula site increased with increasing postarterial cannula pressure, pulsatile amplitude, and flow rate. No surplus hemodynamic energy (SHE) was generated under nonpulsatile mode. Under pulsatile mode, preoxygenator SHE increased with increasing postarterial cannula pressure and pulsatile amplitude, but decreased with increasing flow rate. The i-cor system can provide nonpulsatile and pulsatile flow for neonatal and pediatric ECLS. Pulsatile amplitudes of 2000-3000 rpm are recommended for use in neonatal and pediatric patients.

The purpose of this study was to compare the Capiox FX15 oxygenator with integrated arterial filter to the Capiox RX15 oxygenator with separate Capiox AF125 arterial filter in terms of hemodynamic properties and gaseous microemboli (GME) capturing. Trials were conducted at varying flow rates (2.0 L/min, 3.0 L/min, 4.0 L/min), temperatures (30°C, 35°C), and flow modalities (pulsatile, nonpulsatile). Pressure and flow waveforms were recorded using a custom-made data acquisition system. GME data were recorded using an Emboli Detection and Classification Quantifier after injecting a 5 mL air bolus into the venous line. Maximum instantaneous pre-oxygenator flows reached 7.4 L/min under pulsatile conditions when the roller pump was set to a flow rate of 4 L/min. Mean pressure drops were slightly greater in the FX15 group (P < 0.0001), and the diverted flow from the arterial purge line was slighter greater in the FX15 group at 3 L/min and 4 L/min (P < 0.0001). There was a slight generation of surplus hemodynamic energy (SHE) at the pre-oxygenator site for both oxygenators under "nonpulsatile mode." However, higher pre-oxygenator SHE levels were recorded for both groups with "pulsatile mode." The RX15 and FX15 groups were both able to remove all microemboli from the circuit at 2 L/min and 3 L/min in "nonpulsatile mode." Microemboli were delivered to the patient at 4 L/min with pulsatile flows in both groups. The RX15 oxygenator with separate AF125 arterial filter and FX15 oxygenator with integrated arterial filter performed similarly in terms of hemodynamic performance and microemboli capturing. Pulsatile flows at 4 L/min produced instantaneous flow rates that surpassed the documented maximum flow rates of the oxygenators and might have contributed to the delivery of GME to the pseudo-patient.

The objective of this study was to evaluate the hemodynamic performance and gaseous microemboli (GME) handling ability of a simulated neonatal extracorporeal life support (ECLS) circuit with an in-line continuous renal replacement therapy (CRRT) device. The circuit consisted of a Maquet RotaFlow centrifugal pump or HL20 roller pump, Quadrox-iD Pediatric diffusion membrane oxygenator, 8-Fr arterial cannula, 10-Fr venous cannula, and Better-Bladder (BB) with “Y” connector. A second Quadrox-I Adult oxygenator was added postarterial cannula for GME experiments. The circuit and pseudo-patient were primed with lactated Ringer's solution and packed human red blood cells (hematocrit 40%). All hemodynamic trials were conducted at ECLS flow rates ranging from 200 to 600 mL/min and CRRT flow rate of 75 mL/min at 36°C. Real-time pressure and flow data were recorded with a data acquisition system and GME were detected and characterized using the Emboli Detection and Classification Quantifier System. CRRT was added at distinct locations such that blood entered CRRT between the pump and oxygenator (A), recirculated through the pump (B), or bypassed the pump (C). With the centrifugal pump, all CRRT positions had similar flow rates, mean arterial pressure (MAP), and total hemodynamic energy (THE) loss. With the roller pump, C demonstrated increased flow rates (293.2–686.4 mL/min) and increased MAP (59.4–75.5 mm Hg) (P

Objective: To compare healthcare utilization and outcomes using the Carpenter-Coustan (CC) criteria vs. the National Diabetes Data Group (NDDG) criteria for gestational diabetes mellitus (GDM). Methods: This is a retrospective cohort study. Prior to 8/21/2013, patients were classified as “GDM by CC” if they met criteria. After 8/21/2013, patients were classified as “GDM by NDDG” if they met criteria and “Meeting CC non-GDM” if they met CC, but failed to reach NDDG criteria. “Non-GDM” women did not meet any criteria for GDM. Records were reviewed after delivery. Results: There was a 41% reduction in GDM diagnosed using NDDG compared to CC (P=0.01). There was no significant difference in triage visits, ultrasounds for growth or hospital admissions. Women classified as “Meeting CC non-GDM” were more likely to have preeclampsia than “GDM by CC” women [OR 11.11 (2.7, 50.0), P=0.0006]. Newborns of mothers “Meeting CC non-GDM” were more likely to be admitted to neonatal intensive care units than “GDM by CC” [OR 6.25 (1.7, 33.3), P=0.006], “GDM by NDDG” [OR 5.56 (1.3, 33.3), P=0.018] and “Non-GDM” newborns [OR 6.47 (2.6, 14.8), P=0.0003]. Conclusion: Using the NDDG criteria may increase healthcare costs because while it decreases the number of patients being diagnosed with GDM, it may also increase maternal and neonatal complications without changing maternal healthcare utilization.

Objective To evaluate the feasibility and cardiometabolic effects of mindfulness-based stress reduction (MBSR) in women with overweight or obesity. Methods Eighty-six women with BMI ≥ 25 kg/m2 were randomized to 8 weeks of MBSR or health education and followed for 16 weeks. The primary outcome was the Toronto Mindfulness Scale. Secondary outcomes included the Perceived Stress Scale-10, fasting glucose, and blood pressure. Results Compared to health education, the MBSR group demonstrated significantly improved mindfulness at 8 weeks (mean change from baseline, 4.5 vs. −1.0; P = 0.03) and significantly decreased perceived stress at 16 weeks (−3.6 vs. −1.3, P = 0.01). In the MBSR group, there were significant reductions in fasting glucose at 8 weeks (−8.9 mg/dL, P = 0.02) and at 16 weeks (−9.3 mg/dL, P = 0.02) compared to baseline. Fasting glucose did not significantly improve in the health education group. There were no significant changes in blood pressure, weight, or insulin resistance in the MBSR group. Conclusions In women with overweight or obesity, MBSR significantly reduces stress and may have beneficial effects on glucose. Future studies demonstrating long-term cardiometabolic benefits of MBSR will be key for establishing MBSR as an effective tool in the management of obesity.