Morbidity and mortality following noncardiac surgical procedures among children with autosomal trisomy.

BACKGROUND: Trisomy 13 (T13), trisomy 18 (T18), and trisomy 21 (T21) are the most common autosomal trisomies. One unifying feature of all trisomies is their association with major congenital malformations, which often require life-prolonging surgical procedures. Few studies, mostly among cardiac surgery patients, have examined the outcome of those who undergo surgical procedures. We examined the differences in postsurgical outcomes between the trisomy groups. METHOD: Using the National Surgical Quality Improvement Program dataset, we identified children (<18 years of age) with T13, T18, or T21 who underwent noncardiac surgery (2012-2018). We estimated the incidence of mortality and indicator of resource utilization (unplanned reoperation, unplanned tracheal reintubation, and extended length of hospital stay). RESULTS: Of the 349 158 inpatient surgical cases during the study period, we identified 4202 children with one of the autosomal trisomies of interest (T13: 152; T18: 335; and T21: 3715). The rates of postoperative mortality were substantially higher for T18 and T13 than T21 and nontrisomy children (T18 vs. T21: 11.1% vs. 1.6%, adjusted odds ratio: 5.01, 95%CI: 2.89,8.70, p < .01), (T13 vs. T21: 8.1% vs. 1.6%, adjusted odds ratio: 2.86, 95%CI: 1.25,6.54, p = .01). Children with T18 had the highest rates of extended length of stay (62.7%) and prolonged mechanical ventilation (32.5%). T18 and T13 neonates had the highest surgical mortality burden (T13: 26.5%, T18: 31.8%, and T21: 2.8%). CONCLUSION: Approximately, one-third of T18 and T13 neonates, who had surgery, died, underscoring the lethality of these trisomies and the need for a comprehensive preoperative ethical discussion with families of these children.

Bone Mineral Density and Vitamin D Level Compared to Lifestyle in Resident Physicians.

Due to the demands of resident education and long periods of time spent indoors, resident physicians may have poorer bone quality than would be expected. Forty-four resident physicians underwent dual-energy X-ray absorptiometry (DEXA) and 25-hydroxyvitamin D level testing at our institution. Results were correlated with a survey of self-reported duty hours, physical activity, and sun exposure. The average 25-hydroxyvitamin D level for all participants was 29 ng/dL, which fell into the insufficient range, and 31.5% of all participants were in the deficient range, with a 25-hydroxyvitamin D level < 20 ng/ dL. For the 40 subjects who underwent DEXA, 17 were found to be osteopenic and three were found to be osteoporotic. Greater awareness of bone health, with routine use of vitamin D supplementation and increased time spent outdoors during peak sunlight hours, may be indicated in this cohort.

Assessment Indices of Littoral Habitat Condition for Lakes in Maine and New England, USA.

Littoral habitat is critical for lake biota but is adversely affected by residential shoreland development through the loss and reduced structural complexity of lakeshore vegetation. There currently exists no assessment methodology for evaluating littoral habitat condition of individual lakes in northeastern US. We addressed this assessment need by creating multi-metric indices of littoral habitat condition that focus on lakeshore residential development as the primary stressor. We did this by using habitat metrics derived primarily from National Lake Assessment (NLA) Physical Habitat (PHAB) survey field observations to create Linear Discriminant Analysis (LDA) models that assign lakeshore stations into littoral habitat condition categories. Lake PHAB survey data were used from New England NLA surveys as well as state-level surveys completed in Maine, New Hampshire, and Vermont. Prediction success rates in New England models averaged 83%. The Maine LDA models, which used finer scale survey methods, had an average prediction success rate of 89%. We used 95% bootstrapped confidence intervals to make assessment designations of natural (meeting reference quality), diminished (not meeting reference quality), or intermediate (existing between natural and diminished) littoral habitat condition for each lake. Our results show that efficacious single-lake littoral habitat assessments may be completed within the framework of NLA PHAB methodology, but confidence in assessment results, and therefore better-informed management decisions, can be improved with finer-scale observation data.

Caring for Parturients with Substance Use Disorders.

Parturients with substance use disorder require expertise to manage the complexity of intoxication, withdrawal, and chronic use as well as ensure adequate analgesia throughout labor. Opioid use disorder in pregnancy has increased more than 4-fold in the past decade, with a 50-fold geographic variability that now dwarfs other substance use in this population. Understanding not only the medical but also the public health and criminal justice implications of substance use disorder is essential to providing optimal care to this at-risk population.

Mapping a neutralizing epitope on the SARS coronavirus spike protein: computational prediction based on affinity-selected peptides.

Rapid elucidation of neutralizing antibody epitopes on emerging viral pathogens like severe acute respiratory syndrome (SARS) coronavirus (CoV) or highly pathogenic avian influenza H5N1 virus is of great importance for rational design of vaccines against these viruses. Here we combined screening of phage display random peptide libraries with a unique computer algorithm "Mapitope" to identify the discontinuous epitope of 80R, a potent neutralizing human anti-SARS monoclonal antibody against the spike protein. Using two different types of random peptide libraries which display cysteine-constrained loops or linear 13-15-mer peptides, independent panels containing 42 and 18 peptides were isolated, respectively. These peptides, which had no apparent homologous motif within or between the peptide pools and spike protein, were deconvoluted into amino acid pairs (AAPs) by Mapitope and the statistically significant pairs (SSPs) were defined. Mapitope analysis of the peptides was first performed on a theoretical model of the spike and later on the genuine crystal structure. Three clusters (A, B and C) were predicted on both structures with remarkable overlap. Cluster A ranked the highest in the algorithm in both models and coincided well with the sites of spike protein that are in contact with the receptor, consistent with the observation that 80R functions as a potent entry inhibitor. This study demonstrates that by using this novel strategy one can rapidly predict and identify a neutralizing antibody epitope, even in the absence of the crystal structure of its target protein.

LAGOS-NE: a multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of US lakes.

Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states.LAGOS-NE contains data for 51 101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 data modules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situ measurements of lake water quality for a subset of the lakes from the past 3 decades for approximately 2600-12 000 lakes depending on the variable. The database contains approximately 150 000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from 87 lake water quality data sets from federal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest and most comprehensive databases of its type because it includes both in situ measurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales.

Orthostetrics: Management of Orthopedic Conditions in the Pregnant Patient.

Managing orthopedic conditions in pregnant patients leads to challenges that must be carefully considered so that the safety of both the mother and the fetus is maintained. Both perioperative and intraoperative considerations must be made based on physiologic changes during pregnancy, risks of radiation, and recommendations for monitoring. Operative timing, imaging, and medication selection are also factors that may vary based on trimester and clinical scenario. Pregnancy introduces unique parameters that can result in undesirable outcomes for both mother and fetus if not handled appropriately. Ultimately, pregnant patients offer a distinct challenge to the orthopedic surgeon in that the well-being of 2 patients must be considered in all aspects of care. In addition, not only does pregnancy affect the management of orthopedic conditions but the pregnant state also causes physiologic changes that may actually induce various pathologies. These pregnancy-related orthopedic conditions can interfere with an otherwise healthy pregnancy and should be recognized as possible complications. Although the management of orthopedic conditions in pregnancy is often conservative, pregnancy does not necessarily preclude safely treating pathologies operatively. When surgery is considered, regional anesthesia provides less overall drug exposure to the fetus and less variability in fetal heart rate. Intraoperative fluoroscopy can be used when appropriate, with 360° fetal shielding if possible. Lateral decubitus positioning is ideal to prevent hypotension associated with compression of the inferior vena cava.

Economic impact of syndesmosis hardware removal.

Ankle syndesmosis injuries are commonly seen with 5-10% of sprains and 10% of ankle fractures involving injury to the ankle syndesmosis. Anatomic reduction has been shown to be the most important predictor of clinical outcomes. Optimal surgical management has been a subject of debate in the literature. The method of fixation, number of screws, screw size, and number of cortices are all controversial. Postoperative hardware removal has also been widely debated in the literature. Some surgeons advocate for elective hardware removal prior to resuming full weightbearing. Returning to the operating room for elective hardware removal results in increased cost to the patient, potential for infection or complication(s), and missed work days for the patient. Suture button devices and bioabsorbable screw fixation present other options, but cortical screw fixation remains the gold standard. This retrospective review was designed to evaluate the economic impact of a second operative procedure for elective removal of 3.5mm cortical syndesmosis screws. Two hundred and two patients with ICD-9 code for "open treatment of distal tibiofibular joint (syndesmosis) disruption" were identified. The medical records were reviewed for those who underwent elective syndesmosis hardware removal. The primary outcome measurements included total hospital billing charges and total hospital billing collection. Secondary outcome measurements included average individual patient operative costs and average operating room time. Fifty-six patients were included in the study. Our institution billed a total of $188,271 (USD) and collected $106,284 (55%). The average individual patient operating room cost was $3579. The average operating room time was 67.9 min. To the best of our knowledge, no study has previously provided cost associated with syndesmosis hardware removal. Our study shows elective syndesmosis hardware removal places substantial economic burden on both the patient and the healthcare system.

Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis.

BACKGROUND: Green tea catechins (GTCs) with or without caffeine have been studied in randomized controlled trials (RCTs) for their effect on anthropometric measures and have yielded conflicting results. OBJECTIVE: The objective was to perform a systematic review and meta-analysis of RCTs of GTCs on anthropometric variables, including body mass index (BMI), body weight, waist circumference (WC), and waist-to-hip ratio (WHR). DESIGN: A systematic literature search of MEDLINE, EMBASE, CENTRAL, and the Natural Medicines Comprehensive Database was conducted through April 2009. RCTs that evaluated GTCs with or without caffeine and that reported BMI, body weight, WC, or WHR were included. The weighted mean difference of change from baseline (with 95% CIs) was calculated by using a random-effects model. RESULTS: Fifteen studies (n = 1243 patients) met the inclusion criteria. On meta-analysis, GTCs with caffeine decreased BMI (-0.55; 95% CI: -0.65, -0.40), body weight (-1.38 kg; 95% CI: -1.70, -1.06), and WC (-1.93 cm; 95% CI: -2.82, -1.04) but not WHR compared with caffeine alone. GTC ingestion with caffeine also significantly decreased body weight (-0.44 kg; 95% CI: -0.72, -0.15) when compared with a caffeine-free control. Studies that evaluated GTCs without concomitant caffeine administration did not show benefits on any of the assessed anthropometric endpoints. CONCLUSIONS: The administration of GTCs with caffeine is associated with statistically significant reductions in BMI, body weight, and WC; however, the clinical significance of these reductions is modest at best. Current data do not suggest that GTCs alone positively alter anthropometric measurements.

Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants.

In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.

Immunogenically fit subunit vaccine components via epitope discovery from natural peptide libraries.

Antigenic peptides that bind pathogen-specific Abs are a potential source of subunit vaccine components. To be effective the peptides must be immunogenically fit: when used as immunogens they must elicit Abs that cross-react with native intact pathogen. In this study, antigenic peptides obtained from phage display libraries through epitope discovery were systematically examined for immunogenic fitness. Peptides selected from random peptide libraries, in which the phage-displayed peptides are encoded by synthetic degenerate oligonucleotides, had marginal immunogenic fitness. In contrast, 50% of the peptides selected from a natural peptide library, in which phage display segments of actual pathogen polypeptides, proved very successful. Epitope discovery from natural peptide libraries is a promising route to subunit vaccines.

Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association.

Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261-672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, Kd=32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (Kd=1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.