Search

Author(s): Safavi, Kyan C; Deng, Hao; Driscoll, William; Nikolov, Milcho; Tolia, Kalpan; Wiener-Kronish, Jeanine P | Abstract: BackgroundThe traditional paradigm of hospital surgical ward care consists of episodic bedside visits by providers with periodic perusals of the patient's electronic health record (EHR). Vital signs and laboratory results are directly pushed to the EHR but not to providers themselves. Results that require intervention may not be recognized for hours. Remote surveillance programs continuously monitor electronic data and provide automatic alerts that can be routed to multidisciplinary providers. Such programs have not been explored in surgical general care wards.MethodsWe performed a quality improvement observational study of otolaryngology and ophthalmology patients on a general care ward from October 2017 to March 2019 during nighttime hours (17:00-07:00). The study was initiated due to the loss of on-site anesthesiology resources that historically helped respond to acute physiologic deterioration events. We implemented a remote surveillance software program to continuously monitor patients for severe vital signs and laboratory abnormalities and automatically alert the ward team and a remote critical care anesthesiology team. The primary end point was the true positive rate, defined as the proportion of alerts that were associated with a downstream action that changed the care of the patient. This was determined using systematic chart review. The secondary end point, as a measure of alarm fatigue, was the average number of alerts per clinician shift.ResultsThe software monitored 3926 hospital visits and analyzed 1,560,999 vitals signs and 16,635 laboratories. It generated 151 alerts, averaging 2.6 alerts per week. Of these, 143 (94.7%) were numerically accurate and 8 (5.3%) were inaccurate. Hypoxemia with oxygen saturation l88% was the most common etiology (92, 63%) followed by tachycardia g130 beats per minute (19, 13.3%). Among the accurate alerts, 133 (88.1%) were true positives with an associated clinical action. Actions included a change in management 113 (67.7%), new diagnostic test 26 (15.6%), change in discharge planning 20 (12.0%), and change in level of care to the intensive care unit (ICU) 8 (4.8%). As a measure of alarm fatigue, there were 0.4 alerts per clinician shift.ConclusionsIn a surgical general care ward, a remote surveillance software program that continually and automatically monitors physiologic data streams from the EHR and alerts multidisciplinary providers for severe derangements provided highly actionable alarms at a rate that is unlikely to cause alarm fatigue. Such programs are feasible and could be used to change the paradigm of monitoring.

Objectives Requests for opioid pain medication more than a few weeks after surgery are associated with greater symptoms of depression and cognitive biases regarding pain such as worst-case thinking and fear of painful movement. We sought factors associated with patient desire for more opioid medication and satisfaction with pain alleviation at suture removal after lower extremity surgery. Design Cross sectional study. Setting Enrollment occurred at 1 of 4 orthopaedic offices in an urban setting. Patients/participants At suture removal after lower extremity surgery, 134 patients completed questionnaires measuring catastrophic thinking, ability to reach goals and continue normal activities in spite of pain, symptoms of depression, and magnitude of physical limitations. Main outcome measurements Psychological factors associated with questionnaire-reported patient desire for another opioid prescription, satisfaction with postoperative pain alleviation, and the self-reported number of pills remaining from original opioid prescription. Results In logistic regression, smoking and greater catastrophic thinking were independently associated with desire for opioid refill (R2 = 0.20). Lower satisfaction with pain alleviation was associated with greater catastrophic thinking (R2 = 0.19). The size of surgery (large vs. medium/small procedure) was not associated with pain alleviation or satisfaction with pain alleviation. Conclusions The association between unhelpful cognitive bias regarding pain and request for more opioids reinforces the importance of diagnosing and addressing common misconceptions regarding pain in efforts to help people get comfortable. Level of evidence Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

A long-standing challenge in human microbiome research is achieving the taxonomic and functional resolution needed to generate testable hypotheses about the gut microbiota’s impact on health and disease. With a growing number of live microbial interventions in clinical development, this challenge is renewed by a need to understand the pharmacokinetics and pharmacodynamics of therapeutic candidates. While short-read sequencing of the bacterial 16S rRNA gene has been the standard for microbiota profiling, recent improvements in the fidelity of long-read sequencing underscores the need for a re-evaluation of the value of distinct microbiome-sequencing approaches. We leveraged samples from participants enrolled in a phase 1b clinical trial of a novel live biotherapeutic product to perform a comparative analysis of short-read and long-read amplicon and metagenomic sequencing approaches to assess their utility for generating clinical microbiome data. Across all methods, overall community taxonomic profiles were comparable and relationships between samples were conserved. Comparison of ubiquitous short-read 16S rRNA amplicon profiling to long-read profiling of the 16S-ITS-23S rRNA amplicon showed that only the latter provided strain-level community resolution and insight into novel taxa. All methods identified an active ingredient strain in treated study participants, though detection confidence was higher for long-read methods. Read coverage from both metagenomic methods provided evidence of active-ingredient strain replication in some treated participants. Compared to short-read metagenomics, approximately twice the proportion of long reads were assigned functional annotations. Finally, compositionally similar bacterial metagenome-assembled genomes (MAGs) were recovered from short-read and long-read metagenomic methods, although a greater number and more complete MAGs were recovered from long reads. Despite higher costs, both amplicon and metagenomic long-read approaches yielded added microbiome data value in the form of higher confidence taxonomic and functional resolution and improved recovery of microbial genomes compared to traditional short-read methodologies.

Objective Symptom intensity and magnitude of limitations are highly variable for a given nociception and pathophysiology. As psychological determinants are of great influence to physical wellbeing, we assessed the influence of the protective factor measured and labelled as resilience in upper extremity illness. Methods One hundred and six patients completed a survey of demographics, the Brief Resilience Scale (BRS), the Psychological Adaptation Scale (PAS), an 11-point ordinal measure of pain intensity, and the PROMIS Physical Function (PROMIS PF) Computer Adaptive Test (CAT). Measures of pain intensity and PROMIS PF were repeated 3 months later. We created mediation models using structural equation modeling (SEM) to assess the mediation effect of BRS on the association of PAS and other confounding variables with disability and pain at initial assessment and 3 months later. Results Resiliency does not mediate the association of psychological adaptability with physical limitations and pain intensity at baseline (P = .89 and .82 respectively) or 3 months after enrollment (P = .65 and .72 respectively). Conclusions Positive and protective factors promote beneficial resilience mechanisms that strengthen coping responses to pain and disability. In future studies we should either include more patients to improve power and provide more information about the health benefits of resilience or focus more on mood and self-efficacy on symptoms and limitations in patients with musculoskeletal illness. Level of evidence Prospective, longitudinal cohort study; Level II.

Identifying and tracking microbial strains as microbiomes evolve are major challenges in the field of microbiome research. We utilized a new sequencing kit that combines DNA extraction with PCR amplification of a large region of the rRNA operon and downstream bioinformatic data analysis. Longitudinal microbiome samples of coadmitted twins from two different neonatal intensive care units (NICUs) were analyzed using an ∼2,500-base amplicon that spans the 16S and 23S rRNA genes and mapped to a new, custom 16S-23S rRNA database. Amplicon sequence variants (ASVs) inferred using DADA2 provided sufficient resolution for the differentiation of rRNA variants from closely related but not previously sequenced Klebsiella, Escherichia coli, and Enterobacter strains, among the first bacteria colonizing the gut of these infants after admission to the NICU. Distinct ASV groups (fingerprints) were monitored between coadmitted twins over time, demonstrating the potential to track the source and spread of both commensals and pathogens. The high-resolution taxonomy obtained from long amplicon sequencing enables the tracking of strains temporally and spatially as microbiomes are established in infants in the hospital environment.IMPORTANCE Achieving strain-level resolution is a major obstacle for source tracking and temporal studies of microbiomes. In this study, we describe a novel deep-sequencing approach that provides species- and strain-level resolution of the neonatal microbiome. Using Klebsiella, E. coli, and Enterobacter as examples, we could monitor their temporal dynamics after antibiotic treatment and in pairs of twins. The strain-level resolution, combined with the greater sequencing depth and decreased cost per read of PacBio Sequel 2, enables this advantageous source- and strain-tracking analysis method to be implemented widely across more complex microbiomes.

Understanding and improving obstetrical quality and safety is an important goal of professional societies, and many interventions such as checklists, safety bundles, educational interventions, or other culture changes have been implemented to improve the quality of care provided to obstetrical patients. Although many factors contribute to delivery decisions, a reduced workload has addressed how provider issues such as fatigue or behaviors surrounding impending shift changes may influence the delivery mode and outcomes.The objective was to assess whether intrapartum obstetrical interventions and adverse outcomes differ based on the temporal proximity of the delivery to the attending's shift change.This was a secondary analysis from a multicenter obstetrical cohort in which all patients with cephalic, singleton gestations who attempted vaginal birth were eligible for inclusion. The primary exposure used to quantify the relationship between the proximity of the provider to their shift change and a delivery intervention was the ratio of time from the most recent attending shift change to vaginal delivery or decision for cesarean delivery to the total length of the shift. Ratios were used to represent the proportion of time completed in the shift by normalizing for varying shift lengths. A sensitivity analysis restricted to patients who were delivered by physicians working 12-hour shifts was performed. Outcomes chosen included cesarean delivery, episiotomy, third- or fourth-degree perineal laceration, 5-minute Apgar score of4, and neonatal intensive care unit admission. Chi-squared tests were used to evaluate outcomes based on the proportion of the attending's shift completed. Adjusted and unadjusted logistic models fitting a cubic spline (when indicated) were used to determine whether the frequency of outcomes throughout the shift occurred in a statistically significant, nonlinear pattern RESULTS: Of the 82,851 patients eligible for inclusion, 47,262 (57%) had ratio data available and constituted the analyzable sample. Deliveries were evenly distributed throughout shifts, with 50.6% taking place in the first half of shifts. There were no statistically significant differences in the frequency of cesarean delivery, episiotomy, third- or fourth-degree perineal lacerations, or 5-minute Apgar scores of4 based on the proportion of the shift completed. The findings were unchanged when evaluated with a cubic spline in unadjusted and adjusted logistic models. Sensitivity analyses performed on the 22.2% of patients who were delivered by a physician completing a 12-hour shift showed similar findings. There was a small increase in the frequency of neonatal intensive care unit admissions with a greater proportion of the shift completed (adjusted P=.009), but the findings did not persist in the sensitivity analysis.Clinically significant differences in obstetrical interventions and outcomes do not seem to exist based on the temporal proximity to the attending physician's shift change. Future work should attempt to directly study unit culture and provider fatigue to further investigate opportunities to improve obstetrical quality of care, and additional studies are needed to corroborate these findings in community settings.

BACKGROUND Manual processes for verifying patient identification before blood transfusion and documenting this pretransfusion safety check are prone to errors, and compliance with manual systems is especially poor in urgent operating room settings. An automated, electronic barcode scanner system would be expected to improve pretransfusion verification and documentation. METHODS Audits were conducted of blood transfusion documentation under a manual paper system from January to October 2014. An electronic barcode scanning system was developed to streamline transfusion safety checking and automate documentation. This system was implemented in 58 operating rooms between October and December 2014, with follow-up compliance audits through December 2015. The association of barcode scanner implementation with transfusion documentation compliance was assessed using an interrupted time series analysis. Anesthesia providers were surveyed regarding their opinions on the electronic system. In mid-2016, the scanning system was modified to transfer from the Metavision medical record system to Epic OpTime. Follow-up analysis assessed performance of this system within Epic during 2017. RESULTS In an interrupted time series analysis, the proportion of units with compliant documentation was estimated to be 19.6% (95% confidence interval [CI], 10.7-25.6) the week before scanner implementation, and 74.4% (95% CI, 59.4-87.4) the week after implementation. There was a significant postintervention level change (odds ratio 10.80, 95% CI, 6.31-18.70; P < .001) and increase in slope (odds ratio 1.14 per 1-week increase, 95% CI, 1.11-1.17; P < .001). After implementation, providers chose to use the new electronic system for 98% of transfusions. Across the 2 years analyzed (15,997 transfusions), the electronic system detected 45 potential transfusion errors in 27 unique patients, and averted transfusion of 36 mismatched blood products into 20 unique patients. A total of 69%, 86%, and 88% of providers reported the electronic system improved patient safety, blood transfusion workflow, and transfusion documentation, respectively. When providers used the barcode scanner, no transfusion errors or reactions were reported. The scanner system was successfully transferred from Metavision to Epic without retraining staff or changing workflows. CONCLUSIONS A barcode-based system designed for easy integration to different commonly used anesthesia information management systems was implemented in a large urban academic hospital. The system allows a single user with the assistance of a software system to perform and document pretransfusion safety verification. The system improved transfusion documentation compliance, averted potential transfusion errors, and became the preferred method of blood transfusion safety checking.

BACKGROUND: Asian Americans (AAs) are more likely to use complementary and alternative medicine (CAM) compared to other race/ethnicities, yet previous studies have conflicting results. METHODS: The 2012 National Health Interview Survey data was analyzed to investigate AA’s (n=2,214) CAM use for treatment. AAs were divided into four subgroups: Chinese, Asian Indian, Filipino, and Other Asian. RESULTS: Only 9% of AAs reported using CAM for treatment, with 6% indicating CAM use specifically for chronic conditions. This could be a form of medical pluralism, a mixture of Eastern and Western health approaches. The “Other Asian” subgroup reported highest use of CAM for treatment. Significant predictors included age (≥65 years) and high educational attainment ((≥college degree). Sociodemographic factors were also significant predictors within Asian subgroups. CONCLUSION: Further investigation of this and other forms of medical pluralism among AAs are needed to explore potential cofounders and risks like underreporting, CAM schedules/dosages, cultural influences, and CAM’s impact on one’s health.

BACKGROUND: Adverse childhood experiences (ACEs) affect adult mental health and tend to contribute to greater symptoms of depression and more frequent suicide attempts. Given the relationship between symptoms of depression and patient-reported outcomes (PROs), adversity in childhood might be associated with PROs in patients seeking care for musculoskeletal problems, but it is not clear whether in fact there is such an association among patients seeking care in an outpatient, upper extremity orthopaedic practice. QUESTIONS/PURPOSES: (1) Are ACE scores independently associated with variation in physical limitations measured among patients seen by an orthopaedic surgeon? (2) Are ACE scores independently associated with variations in pain intensity? (3) What factors are associated with ACE scores when treated as a continuous variable or as a categorical variable? METHODS: We prospectively enrolled 143 adult patients visiting one of seven participating orthopaedic surgeons at three private and one academic orthopaedic surgery offices in a large urban area. We recorded their demographics and measured ACEs (using a validated 10-item binary questionnaire that measured physical, emotional, and sexual abuse in the first 18 years of life), magnitude of physical limitations, pain intensity, symptoms of depression, catastrophic thinking, and health anxiety. There were 143 patients with a mean age of 51 years, 62 (43%) of whom were men. In addition, 112 (78%) presented with a specific diagnosis and most (n = 79 [55%]) had upper extremity symptoms. We created one logistic and three linear regression models to test whether age, gender, race, marital status, having children, level of education, work status, insurance type, comorbidities, body mass index, smoking, site of symptoms, type of diagnosis, symptoms of depression, catastrophic thinking, and health anxiety were independently associated with (1) the magnitude of limitations; (2) pain intensity; (3) ACE scores on the continuum; and (4) ACE scores categorized (< 3 or ≥ 3). We calculated a priori that to detect a medium effect size with 90% statistical power and α set at 0.05, a sample of 136 patients was needed for a regression with five predictors if ACEs would account for ≥ 5% of the variability in physical function, and our complete model would account for 15% of the overall variability. To account for 5% incomplete responses, we enrolled 143 patients. RESULTS: We found no association between ACE scores and the magnitude of physical limitations measured by Patient-Reported Outcomes Measurement Information System Physical Function (p = 0.67; adjusted R(2) = 0.55). ACE scores were not independently associated with pain intensity (Pearson correlation [r] = 0.11; p = 0.18). Greater ACE scores were independently associated with diagnosed mental comorbidities both when analyzed on the continuum (regression coefficient [β] = 1.1; 95% confidence interval [CI], 0.32-1.9; standard error [SE] 0.41; p = 0.006) and categorized (odds ratio [OR], 3.3; 95% CI, 1.2-9.2; SE 1.7; p = 0.024), but not with greater levels of health anxiety (OR, 1.1; 95% CI, 0.90-1.3; SE 0.096; p = 0.44, C statistic = 0.71), symptoms of depression (ACE < 3 mean ± SD = 0.73 ± 1.4; ACE ≥ 3 = 1.0 ± 1.4; p = 0.29) or catastrophic thinking (ACE < 3 = 3.6 ± 3.5; ACE ≥ 3 = 4.9 ± 5.1; p = 0.88). CONCLUSIONS: ACEs may not contribute to greater pain intensity or magnitude of physical limitations unless they are accompanied by greater health anxiety or less effective coping strategies. Adverse events can contribute to anxiety and depression, but perhaps they sometimes lead to development of resilience and effective coping strategies. Future research might address whether ACEs affect symptoms and limitations in younger adult patients and patients with more severe musculoskeletal pathology such as major traumatic injuries. LEVEL OF EVIDENCE: Level II, prognostic study.

Background Cervical cancer remains the leading cause of cancer and mortality in low-resource areas with healthcare personnel shortages. Visual inspection is a low-resource alternative method of cervical cancer screening in areas with limited access to healthcare. Objectives To assess accuracy of visual inspection performed by community health workers (CHWs) and licensed providers, and the effect of provider training on visual inspection accuracy. Search strategy Five databases and four websites were queried for studies published in English up to December 31, 2015. Derivations of "cervical cancer screening" and "visual inspection" were search terms. Selection criteria Visual inspection screening studies with provider definitions, colposcopy reference standards, and accuracy data were included. Data collection and analysis A priori variables were extracted by two independent reviewers. Bivariate linear mixed-effects models were used to compare visual inspection accuracy. Main results Provider type was a significant predictor of visual inspection sensitivity (P=0.048); sensitivity was 15 percentage points higher among CHWs than physicians (P=0.014). Components of provider training were significant predictors of sensitivity and specificity. Conclusions Community-based visual inspection programs using adequately trained CHWs could reduce barriers and expand access to screening, thereby decreasing cervical cancer incidence and mortality for women at highest risk and those living in remote areas with limited access to healthcare personnel.

The convergence of multiple recent developments in health care information technology and monitoring devices has made possible the creation of remote patient surveillance systems that increase the timeliness and quality of patient care. More convenient, less invasive monitoring devices, including patches, wearables, and biosensors, now allow for continuous physiological data to be gleaned from patients in a variety of care settings across the perioperative experience. These data can be bound into a single data repository, creating so-called data lakes. The high volume and diversity of data in these repositories must be processed into standard formats that can be queried in real time. These data can then be used by sophisticated prediction algorithms currently under development, enabling the early recognition of patterns of clinical deterioration otherwise undetectable to humans. Improved predictions can reduce alarm fatigue. In addition, data are now automatically queriable on a real-time basis such that they can be fed back to clinicians in a time frame that allows for meaningful intervention. These advancements are key components of successful remote surveillance systems. Anesthesiologists have the opportunity to be at the forefront of remote surveillance in the care they provide in the operating room, postanesthesia care unit, and intensive care unit, while also expanding their scope to include high-risk preoperative and postoperative patients on the general care wards. These systems hold the promise of enabling anesthesiologists to detect and intervene upon changes in the clinical status of the patient before adverse events have occurred. Importantly, however, significant barriers still exist to the effective deployment of these technologies and their study in impacting patient outcomes. Studies demonstrating the impact of remote surveillance on patient outcomes are limited. Critical to the impact of the technology are strategies of implementation, including who should receive and respond to alerts and how they should respond. Moreover, the lack of cost-effectiveness data and the uncertainty of whether clinical activities surrounding these technologies will be financially reimbursed remain significant challenges to future scale and sustainability. This narrative review will discuss the evolving technical components of remote surveillance systems, the clinical use cases relevant to the anesthesiologist's practice, the existing evidence for their impact on patients, the barriers that exist to their effective implementation and study, and important considerations regarding sustainability and cost-effectiveness.

BACKGROUND: It seems common for patients to conceive of care in physical terms, such as medications, injections, and procedures rather than advice and support. Clinicians often encounter patients who seem to prefer more testing or invasive treatments than expertise supports. We wanted to determine whether patients unconsciously associate suggestions for invasive treatments with better care. QUESTIONS/PURPOSES: (1) Do patients have (A) an implicit preference and (B) an expressed preference for a physical intervention (such as a pill, an injection, or surgery) over supportive care (such as reassurance and education)? (2) What factors are independently associated with both an implicit and an expressed preference for a physical intervention over supportive care? (3) Is there a relationship between a patient’s implicit preference toward or away from a physical intervention and his/her expressed preference on that subject? METHODS: In this study, we approached 129 new patients in a large urban area visiting one of 13 participating surgeons divided among six upper and lower extremity specialist offices. After excluding four patients based on our exclusion criteria, 125 patients (97%) completed a survey of demographics and their expressed preference about receiving either physical treatment or support. Treatment was defined as any surgery, procedure, injection, or medication; support was defined as reassurance, conversation, and education, but no physical treatment. Patients then completed the Implicit Association Test (IAT) to evaluate implicit preferences toward treatment or support. Although other IATs have been validated in numerous studies, the IAT used in this study was specifically made for this study. Scores (D scores) range from -2 to 2, where 0 indicates no implicit preference, positive scores indicate a preference toward receiving a physical treatment is good care, and negative scores indicate a preference toward receiving supportive care is good care. According to the original IAT, break points for a slight (± 0.15 to 0.35), moderate (± 0.35 to 0.65), and strong preference (± 0.65 to 2) were selected conservatively according to psychological conventions for effect size. Patients’ mean age was 50 ± 15 years (range, 18–79 years) and 56 (45%) were men. The patients had a broad spectrum of upper and lower extremity musculoskeletal conditions, ranging from trigger finger to patellofemoral syndrome. RESULTS: We found a slight implicit association of good care with support (D = -0.17 ± 0.62; range, -2 to 1.2) and an expressed preference for physical treatment (mean score = 0.63 ± 2.0; range, -3 to 3). Patients who received both physical and supportive treatment had greater implicit preference for good care, meaning supportive care, than patients receiving physical care alone (β = -0.42; 95% CI, -0.73 to -0.11; p = 0.008; semipartial R(2) = 0.04; adjusted R(2) full model = 0.13). Gender was independently associated with a greater expressed preference for physical treatment, with men expressing this preference more than women (β = 1.0; 95% CI, 0.31–1.7; p = 0.005; semipartial R(2) = 0.06; adjusted R(2) full model = 0.08); receiving supportive treatment was independently associated with more expressed preference for support (β = -0.98; 95% CI, -1.7 to -0.23; p = 0.011; semipartial R(2) = 0.05). An expressed preference for treatment was not associated with implicit preference (β = 0.01; 95% CI, -0.04 to 0.06; p = 0.721). CONCLUSIONS: Although surgeons may sometimes feel pressured toward physical treatments, based on our results and cutoff values, the average patient with upper or lower extremity symptoms has a slight implicit preference for supportive treatment and would likely be receptive. LEVEL OF EVIDENCE: Level II, prognostic study.

BACKGROUND: While there are well-accepted standards for the diagnosis of arrested active-phase labor, the definition of a "failed" induction of labor remains less certain. One approach to diagnosing a failed induction is based on the duration of the latent phase. However, a standard for the minimum duration that the latent phase of a labor induction should continue, absent acute maternal or fetal indications for cesarean delivery, remains lacking. OBJECTIVE: The objective of this study was to determine the frequency of adverse maternal and perinatal outcomes as a function of the duration of the latent phase among nulliparous women undergoing labor induction. METHODS: This study is based on data from an obstetric cohort of women delivering at 25 U.S. hospitals from 2008-2011. Nulliparous women who had a term singleton gestation in the cephalic presentation were eligible for this analysis if they underwent a labor induction. Consistent with prior studies, the latent phase was determined to begin once cervical ripening had ended, oxytocin was initiated and rupture of membranes (ROM) had occurred, and was determined to end once 5 cm dilation was achieved. The frequencies of cesarean delivery, as well as of adverse maternal (e.g., cesarean delivery, postpartum hemorrhage, chorioamnionitis) and perinatal outcomes (e.g., a composite frequency of either seizures, sepsis, bone or nerve injury, encephalopathy, or death), were compared as a function of the duration of the latent phase (analyzed with time both as a continuous measure and categorized in 3-hour increments). RESULTS: A total of 10,677 women were available for analysis. In the vast majority (96.4%) of women, the active phase had been reached by 15 hours. The longer the duration of a woman's latent phase, the greater her chance of ultimately undergoing a cesarean delivery (P

Background Ankle valgus is frequently encountered in skeletally immature patients in association with a variety of musculoskeletal disorders. Guided growth with temporary medial malleolar transphyseal screw (MMS) hemiepiphysiodesis is an established surgical treatment capable of correcting the angular deformity, but is often complicated by symptomatic screw head prominence and difficult hardware removal. Tension-band plate (TBP) hemiepiphysiodesis has recently been advocated as an alternative; however, the relative efficacy of these 2 techniques has not been directly investigated. Thus, the purpose of this study was to compare MMS and TBP in treatment of pediatric ankle valgus deformity. Methods Medical records and radiographs of all patients undergoing distal tibial medial hemiepiphysiodesis for ankle valgus between January 1, 2005 and November 1, 2010 at a pediatric orthopaedic specialty hospital were retrospectively reviewed. Radiographs obtained preoperatively and at 6-month intervals postoperatively were reviewed and the tibiotalar angle was measured. Patient age, sex, underlying diagnosis, concurrent surgical procedures, surgical and postoperative complications, and the presence or absence of symptomatic hardware complaints were documented. Results Sixty ankles in 42 patients met the inclusion criteria, with adequate radiographs and minimum postoperative follow-up of 12 months (mean: 34 mo). Thirty-five ankles were treated with MMS, and 25 with TBP. Good mean correction of the tibiotalar angle was achieved in both groups (MMS: pre-77.1 degrees to post-87.8 degrees over 25.2 mo; TBP: pre-81.3 to post-87.6 over 20.0 mo). The mean rate of correction was faster in ankles treated with MMS than TBP, but differences did not reach statistical significance (0.55 vs. 0.36 degrees/mo, respectively; P=0.057). Complications included 6 hardware-related surgical complications in MMS ankles (17.1%) and 1 in TBP ankles (4.0%). The incidence of symptomatic hardware complaints was low in both groups (MMS, 5.7%; TBP, 0%). Conclusions Both MMS and TBP techniques can result in successful correction of ankle valgus in the growing child. Although the rate of deformity correction may be faster with MMS, TBP seems to be associated with fewer hardware-related complications. This information may aid the clinician in selecting the surgical option most appropriate for each individual patient. Level of evidence Level II-retrospective study.

Background Studies of early-term birth after demonstrated fetal lung maturity show that respiratory and other outcomes are worse with early-term birth (370–386 weeks) even after demonstrated fetal lung maturity when compared with full-term birth (390–406 weeks). However, these studies included medically indicated births and are therefore potentially limited by confounding by the indication for delivery. Thus, the increase in adverse outcomes might be due to the indication for early-term birth rather than the early-term birth itself. Objective We examined the prevalence and risks of adverse neonatal outcomes associated with early-term birth after confirmed fetal lung maturity as compared with full-term birth in the absence of indications for early delivery. Study Design This is a secondary analysis of an observational study of births to 115,502 women in 25 hospitals in the United States from 2008 through 2011. Singleton nonanomalous births at 37–40 weeks with no identifiable indication for delivery were included; early-term births after positive fetal lung maturity testing were compared with full-term births. The primary outcome was a composite of death, ventilator for ≥2 days, continuous positive airway pressure, proven sepsis, pneumonia or meningitis, treated hypoglycemia, hyperbilirubinemia (phototherapy), and 5-minute Apgar Results In all, 48,137 births met inclusion criteria; the prevalence of fetal lung maturity testing in the absence of medical or obstetric indications for early delivery was 0.52% (n = 249). There were 180 (0.37%) early-term births after confirmed pulmonary maturity and 47,957 full-term births. Women in the former group were more likely to be non-Hispanic white, smoke, have received antenatal steroids, have induction, and have a cesarean. Risks of the composite (16.1% vs 5.4%; adjusted odds ratio, 3.2; 95% confidence interval, 2.1–4.8 from logistic regression) were more frequent with elective early-term birth. Propensity scores matching confirmed the increased primary composite in elective early-term births: adjusted odds ratios, 4.3 (95% confidence interval, 1.8–10.5) for 1:1 and 3.5 (95% confidence interval, 1.8–6.5) for 1:2 matching. Among components of the primary outcome, CPAP use and hyperbilirubinemia requiring phototherapy were significantly increased. Transient tachypnea of the newborn, neonatal intensive care unit admission, and prolonged neonatal intensive care unit stay (>2 days) were also increased with early-term birth. Conclusion Even with confirmed pulmonary maturity, early-term birth in the absence of medical or obstetric indications is associated with worse neonatal respiratory and hepatic outcomes compared with full-term birth, suggesting relative immaturity of these organ systems in early-term births.

The cause of the awareness under general anesthesia often cannot be definitely determined from retrospective reviews of handwritten records, examinations of equipment, or interviews with clinicians. Failure to deliver the intended concentrations of anesthetic agents to the patient is one possible contributing cause for awareness. An advantage of an automated Anesthesia Information Management System (AIMS) is its ability to electronically capture and preserve case data that might otherwise be lost. We reviewed the AIMS records of 3 anesthetics in which intraoperative awareness was felt to have probably occurred. The details of the reported awareness event were temporally correlated with the anesthetic gas concentrations in an effort to determine if low concentrations were contributing factors. The data captured by the AIMS revealed low levels of inspired or expired inhalation agents during the intervals correlating with apparent patient recall. The findings suggest that failure to deliver sufficient concentrations of anesthetic gases permitted awareness events in these cases. Thus data from automated anesthesia information management in the operating room may help identify causes of awareness, and means to prevent awareness can be instituted.

Studies of the accuracy and completeness of handwritten anesthesia records demonstrate deficiencies in documentation, suggesting that the quality of anesthesia records can be improved.We reviewed all electronic anesthesia records generated during a 1-month period at our institution to ascertain completion rates for six clinical documentation elements: allergies, IV access, electrocardiogram rhythm, ease of mask ventilation, laryngoscopic grade of view, and insertion depth of the endotracheal tube.Of 2838 records, 64% had the necessary free text remark in the allergy element. The free text required to complete endotracheal tube depth documentation appeared in 538 of 918 cases in which the patient was tracheally intubated (59%). Free text documentation of the electrocardiogram rhythm diagnosis appeared at least once in 86% of records. Documentation of mask ventilation characteristics was entered by touch screen from a pick list and was expected in 781 records but appeared in 664 records (85%). Laryngoscopic grade of view documentation was also selected by touch screen and expected in 883 records but present in 811 cases (92%). Any notation of IV access appeared in 84% of records.We found that electronic clinical anesthesia documentation was often incomplete. Dependence on free text remarks and the record keeping system's inability to automatically present entries in logical sequences consistent with workflow were associated with incomplete data entry. Our results suggest that the user interface for data entry, and the logic that an electronic system uses for preventing omissions and inconsistencies, merit further study and development in order to facilitate clinically useful documentation.

Background Variations exist in compliance with NCCN Guidelines. Prior reports of adherence to NCCN Guidelines contain limitations because of lack of contemporary review and incomplete listing of reasons for noncompliance. Purpose To assess institutional compliance and assist national quality improvement strategies through identifying valid reasons for noncompliance. Methods Compliance with NCCN Guidelines was recorded prospectively using electronic synoptic templates for patients with newly diagnosed breast cancer treated at a single institution between January 2010 and December 2011. Compliance with NCCN Guidelines was recorded. The accuracy of real-time synoptic auditing methods compared with retrospective chart review and reasons for noncompliance was assessed. SAS 9.3 software was used for data analysis. Results Compliance with NCCN Guidelines among 395 patients was 94% for initial staging evaluation, 97% for surgery, 91% for chemotherapy, 89% for hormone therapy, 91% for radiation therapy, 85% for follow-up, and 100% for determination of estrogen receptor/progesterone receptor and HER2 status. Age, comorbidities, and stage influenced guideline compliance. The most common reasons for noncompliance were patient refusal, patient choice after shared decision-making, and overuse of testing. Synoptic templated reporting was accurate in 97% patients. Conclusions High compliance with NCCN Guidelines was demonstrated. Reasons for noncompliance were identifiable. Compliance and nonadherence can be evaluated quickly with electronic synoptic reporting. This allows real-time action plans to address quality concerns and aids national risk adjustment for comparison and benchmarking.

Objective We sought to evaluate whether the presence of condition-specific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes. Study Design This was a cohort study of a random sample of deliveries performed at 25 hospitals over 3 years. Condition-specific protocols were collected from all hospitals and categorized independently by 2 authors. Data on maternal and neonatal outcomes, as well as data necessary for risk adjustment were collected. Risk-adjusted outcomes were compared according to whether the patient delivered in a hospital with condition-specific obstetric protocols at the time of delivery. Results Hemorrhage-specific protocols were not associated with a lower rate of postpartum hemorrhage or with fewer cases of estimated blood loss >1000 mL. Similarly, in the presence of a shoulder dystocia protocol, there were no differences in the frequency of shoulder dystocia or number of shoulder dystocia maneuvers used. Conversely, preeclampsia-specific protocols were associated with fewer intensive care unit admissions (odds ratio, 0.28; 95% confidence interval, 0.18–0.44) and fewer cases of severe maternal hypertension (odds ratio, 0.86; 95% confidence interval, 0.77–0.96). Conclusion The presence of condition-specific obstetric protocols was not consistently shown to be associated with improved risk-adjusted outcomes. Our study would suggest that the presence or absence of a protocol does not matter and regulations to require protocols are not fruitful.

OBJECTIVE To determine whether exercise training in combination with metformin improves cardiovascular risk indices and insulin in comparison to metformin alone among HIV-infected patients. METHODS AND DESIGN We conducted a prospective, randomized, 3-month study of HIV patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution. Subjects received metformin alone or metformin and exercise training consisting of 1 h of aerobic and resistance training three times a week. Cardiovascular parameters, including blood pressure and endurance during sub-maximal stress testing, body composition, strength, insulin and other biochemical parameters were determined. RESULTS Thirty-seven patients were randomized and 25 subjects completed the study. Subjects receiving exercise training and metformin demonstrated significant decreases in median waist-to-hip ratio [-0.02 (-0.06, -0.01) (median (interquartile range) versus -0.01 (0.03, 0.02), P = 0.026], resting systolic [-12 (-20, -4) versus 0 (-11, 11), P = 0.012] and diastolic blood pressures [-10 (-14, -8) versus 0 (-7, 8), P = 0.001], increased thigh muscle cross-sectional area [3 (-3, 12) versus -7 (-11, 0), P = 0.015], and improved exercise time [3 (0, 4) versus 0 (-1, 1), P = 0.045] compared with subjects receiving metformin alone. Fasting insulin and insulin area under the curve decreased significantly more in the exercise and metformin group (P < 0.05). Lipids and resting lactate did not change significantly between treatment groups. CONCLUSIONS These data demonstrate that exercise training in combination with metformin significantly improves cardiovascular and biochemical parameters more than metformin alone in HIV-infected patients with fat redistribution and hyperinsulinemia. Combined treatment was safe, well tolerated and may be a useful strategy to decrease cardiovascular risk in this population.

Fundamental to most genetic analysis is availability of genomic DNA of adequate quality and quantity. Because DNA yield from human samples is frequently limiting, much effort has been invested in developing methods for whole genome amplification (WGA) by random or degenerate oligonucleotide-primed PCR. However, existing WGA methods like degenerate oligonucleotide-primed PCR suffer from incomplete coverage and inadequate average DNA size. We describe a method, termed multiple displacement amplification (MDA), which provides a highly uniform representation across the genome. Amplification bias among eight chromosomal loci was less than 3-fold in contrast to 4–6 orders of magnitude for PCR-based WGA methods. Average product length was >10 kb. MDA is an isothermal, strand-displacing amplification yielding about 20–30 μg product from as few as 1–10 copies of human genomic DNA. Amplification can be carried out directly from biological samples including crude whole blood and tissue culture cells. MDA-amplified human DNA is useful for several common methods of genetic analysis, including genotyping of single nucleotide polymorphisms, chromosome painting, Southern blotting and restriction fragment length polymorphism analysis, subcloning, and DNA sequencing. MDA-based WGA is a simple and reliable method that could have significant implications for genetic studies, forensics, diagnostics, and long-term sample storage.

Estrogen signaling is mediated by ERα and -β. ERs are converted from an inactive form to a transcriptionally active state through conformational changes induced by ligand and estrogen-responsive element (ERE) sequences. We show here that ERα and ERβ bind to an ERE independently from ER ligands. We found that although the binding affinity of ERβ for an ERE is 2-fold lower than that of ERα, both ERs use the same nucleotides for DNA contacts. We show that both EREs and ligands are independent modulators of ER conformation. Specifically, the ERE primarily determines the receptor-DNA affinity, whereas the structure of the ER ligand dictates the affinity of ER for particular cofactors. We found that the ligand-dependent cofactor transcriptional intermediary factor-2, through a distinct surface, also interacts with ERα preferentially and independently of ligand. The extent of interaction, however, is dependent upon the ER-ERE affinity. In transfected cells, ERα is more transcriptionally active than ERβ. The ERE sequence, however, determines the potency of gene induction when either ER subtype binds to an agonist. Antagonists prevent ERs from inducing transcription independently from ERE sequences. Thus, ERE- and ligand-induced structural changes are independent determinants for the recruitment of cofactors and transcriptional responses. The ability of ERα to differentially recruit a cofactor could contribute to ER subtype-specific gene responses.

Background: Process improvement in healthcare delivery settings can be difficult, even when there is consensus among clinicians about a clinical practice or desired outcome. Airway management is a medical intervention fundamental to the delivery of anesthesia care. Like other medical interventions, a detailed description of the management methods should be documented. Despite this expectation, airway documentation is often insufficient. The authors hypothesized that formal adoption of process improvement methods could be used to increase the rate of “complete” airway management documentation. Methods: The authors defined a set of criteria as a local practice standard of “complete” airway management documentation. The authors then employed selected process improvement methodologies over 13 months in three iterative and escalating phases to increase the percentage of records with complete documentation. The criteria were applied retrospectively to determine the baseline frequency of complete records, and prospectively to measure the impact of process improvements efforts over the three phases of implementation. Results: Immediately before the initial intervention, a retrospective review of 23,011 general anesthesia cases over 6 months showed that 13.2% of patient records included complete documentation. At the conclusion of the 13-month improvement effort, documentation improved to a completion rate of 91.6% (P < 0.0001). During the subsequent 21 months, the completion rate was sustained at an average of 90.7% (SD, 0.9%) across 82,571 general anesthetic records. Conclusion: Systematic application of process improvement methodologies can improve airway documentation and may be similarly effective in improving other areas of anesthesia clinical practice.

Estrogen-induced signaling mediated by estrogen receptors (ERs) is also affected by aberrant ERs that act as constitutively active or dominant negative modulators. Variant ERs can contribute to carcinogenesis and to the loss of estrogen responsiveness, rendering antiestrogen therapy ineffective. Determining target gene response during co-synthesis of different ER species is difficult, because dimers formed in the presence of more than one ER species are a heterogenous population of homo- or heterodimers. We engineered a homofusion ERalpha as a prototype single-chain receptor by genetically conjugating two ER monomers into a covalently fused single-chain protein to obtain a homogeneous population. This permits analysis of symmetrical or asymmetrical mutations that simulate variant homo- and heterodimers. Although a monomer, the homofusion receptor exhibited similar biochemical and functional properties to the dimeric ERalpha. We used activation function-2 (AF2) defective mutants as a model in either one or both receptor domains for a dominant-negative phenotype by suppressing the reporter activity induced by the WT receptor. When co-expressed with ERalpha, the fusion variant deficient in both AF2 functions suppressed the reporter activity effectively induced by ERalpha. These results show the utility of fusion receptors as models for generation of receptor-based agonists and antagonists.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), nucleocapsid protein (NC), genomic RNA, and the growing DNA strand all influence the copying of the HIV-1 RNA genome into DNA. A detailed understanding of these activities is required to understand the process of reverse transcription. HIV-1 viral DNA is initiated from a tRNA 3 Lys primer bound to the viral genome at the primer binding site. The U3 and R regions of the RNA genome are the first sequences to be copied. The TAR hairpin, a structure found within the R region of the viral genome, is the site of increased RT pausing, RNase H activity, and RT dissociation. Template RNA was digested approximately 17 bases behind the site where polymerase paused at the base of TAR. In most template RNAs, this was the only cleavage made by the RT responsible for initiating polymerization. If the RT that initiated DNA synthesis dissociated from the base of the TAR hairpin and an RT rebound at the end of the primer, there was competition between the polymerase and RNase H activities. After the complete heteroduplex was formed, there were additional RNase H cleavages that did not involve polymerization. Levels of NC that prevented TAR DNA self-priming did not protect genomic RNA from RNase H digestion. RNase H digestion of the 100-bp heteroduplex produced a 14-base RNA from the 5′ end of the RNA that remained annealed to the 3′ end of the minus-strand strong-stop DNA only if NC was present in the reaction.

The estrogen receptor (ER) is a transcription factor that binds to a specific DNA sequence found in the regulatory regions of estrogen-responsive genes, called the estrogen response element (ERE). Many genes that contain EREs have been identified, and most of these EREs contain one or more changes from the core consensus sequence, a 13-nucleotide segment with 10 nucleotides forming an inverted repeat. A number of genes have multiple copies of these imperfect EREs. In order to understand why natural EREs have developed in this manner, we have attempted to define the basic sequence requirements for ER binding. To this end, we measured the binding of homodimeric ER to a variety of nonconsensus EREs. We discovered that an ERE containing even a single change from the consensus may be unable to bind ER. However, an ERE with two changes from the consensus may be capable of binding avidly to ER in the context of certain flanking sequences. We found that changes in the sequences flanking a nonconsensus ERE can greatly alter ER-ERE affinity, either positively or negatively. Careful study of sequences flanking a series of EREs made it possible to develop rules that predict whether ER binds to a given natural ERE and also to predict the relative amounts of binding when comparing two EREs.

Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) was identified as a low abundance protein in bovine uterus that co-purified with estrogen receptor (ER) in a ligand-independent manner and was separated from the ER by its lower retention on estrogen response element (ERE)-Sepharose. In gel mobility shift assays, COUP-TF bound as an apparent dimer to ERE and ERE half-sites. COUP-TF bound to an ERE half-site with high affinity,K d = 1.24 nm. In contrast, ER did not bind a single ERE half-site. None of the class II nuclear receptors analyzed, i.e. retinoic acid receptor, retinoid X receptor, thyroid receptor, peroxisome proliferator-activated receptor, or vitamin D receptor, were constituents of the COUP-TF·DNA binding complex detected in gel mobility shift assays. Direct interaction of COUP-TF with ER was indicated by GST “pull-down” and co-immunoprecipitation assays. The nature of the ER ligand influenced COUP-TF-ERE half-site binding. When ER was liganded by the antiestrogen 4-hydroxytamoxifen (4-OHT), COUP-TF-half-site interaction decreased. Conversely, COUP-TF transcribed and translated in vitroenhanced the ERE binding of purified estradiol (E2)-liganded ER but not 4-OHT-liganded ER. Co-transfection of ER-expressing MCF-7 human breast cancer cells with an expression vector for COUP-TFI resulted in a dose-dependent inhibition of E2-induced expression of a luciferase reporter gene under the control of three tandem copies of EREc38. The ability of COUP-TF to bind specifically to EREs and half-sites, to interact with ER, and to inhibit E2-induced gene expression suggests COUP-TF regulates ER action by both direct DNA binding competition and through protein-protein interactions.

Background: Ankle valgus is encountered in children with a variety of congenital musculoskeletal disorders, including multiple hereditary exostoses (MHE). Guided growth with temporary distal tibial medial hemiepiphysiodesis (DTMH) may correct the deformity; however, exostoses about the ankle commonly observed in MHE patients may hinder correction and increase the risk of recurrence. Thus, the purpose of this study was to review the outcomes of DTMH in treatment of ankle valgus in MHE versus other diagnosis (non-MHE). Methods: Medical records and radiographs of patients undergoing DTMH for ankle valgus between January 1, 2005, and November 1, 2010, at a single pediatric orthopedic hospital were retrospectively analyzed. Radiographs obtained preoperatively and at 6-month intervals postoperatively were reviewed and the tibiotalar angle was measured. Results: Fifty-eight ankles in 41 patients met inclusion criteria, with minimum follow-up of 12 months (mean, 34 months). Mean age was 10 years (range, 4-14 years). MHE was the most common underlying diagnosis (19 ankles, 33%). The rate of tibiotalar angle correction (mean ± standard deviation) with hardware in place was 0.37 ± 0.28 deg/mo in MHE ankles and 0.51 ± 0.42 deg/mo in non-MHE ankles ( P = .161). Following hardware removal, the rate of recurrence was faster in MHE (0.29 ± 0.25 deg/mo) compared with non-MHE ankles (0.12 ± 0.19 deg/mo) ( P = .059), and more total recurrent valgus deformity was observed in MHE (7.8 ± 8.2 degrees) than non-MHE ankles (3.4 ± 4.6 degrees) ( P = .08) over a similar follow-up period (mean 23.4 vs 23.6 months, respectively), with differences approaching statistical significance. Conclusion: MHE is a common cause of ankle valgus in children. Guided growth interventions in this population can be successful but require special consideration given the potential for relatively gradual deformity correction and rapid recurrence following hardware removal in the skeletally immature. Level of Evidence: Level III, retrospective comparative study.

Conformational differences between type I antiestrogen-liganded estrogen receptor and estradiol (E2)-liganded estrogen receptor (ER) are thought to be responsible for differentiating agonist versus antagonist ER activity at individual genes. To examine the impact of ER ligand on estrogen-response element (ERE) binding kinetics and receptor conformation, we quantitated the effect of site-directed, ER-specific antibodies raised against synthetic peptides corresponding to the DNA-binding domain of human ER on ER-ERE binding in vitro. Although 4-hydroxytamoxifen-liganded-ER (4-OHT-ER) and E2-ER bind a consensus ERE with equal high affinity, the stoichiometry of 4-OHT-ER-ERE binding at saturation is approximately 50% lower than that of E2-ER binding to all ERE sequences tested. In contrast, the ERE binding stoichiometry of tamoxifen aziridine-liganded ER (TAz-ER) is identical to that of E2-ER: one receptor dimer bound per ERE. The difference in binding stoichiometry is caused by dissociation of one molecule of 4-OHT from the ER as the dimeric receptor binds DNA. Addition of low concentrations of ER-specific polyclonal antibodies AT3A or AT3B prevented 4-OHT ligand dissociation, yielding an increase in specific 4-OHT-ER-ERE binding to a level equal to that of E2-ER- or TAz-ER-ERE binding. However, higher amounts of AT3A or AT3B inhibited specific ERE binding of both 4-OHT- and E2-ER. We conclude that differences in ER conformation when liganded with 4-OHT versus E2 are revealed by these antibodies and that such differences in receptor conformation may influence subsequent interaction of the receptor with other proteins necessary for transactivation.

Background Cesarean delivery in the second stage of labor is common, whereas the frequency of operative vaginal delivery has been declining. However, data comparing outcomes for attempted operative vaginal delivery vs cesarean in the second stage are scant. Previous studies that examine operative vaginal delivery have compared it to a baseline risk of complications from a spontaneous vaginal delivery and cesarean delivery. However, when a woman has a need for intervention in the second stage, spontaneous vaginal delivery is not an option she or the provider can choose. Thus, the appropriate clinical comparison is cesarean vs operative vaginal delivery. Objective Our objective was to compare outcomes by the first attempted operative delivery (vacuum, forceps vs cesarean delivery) in patients needing second-stage assistance at a fetal station of +2 or below. Study Design We conducted secondary analysis of an observational obstetric cohort in 25 academically affiliated US hospitals over a 3-year period. A subset of ≥37 weeks, nonanomalous, vertex, singletons, with no prior vaginal delivery who reached a station of +2 or below and underwent an attempt at an operative delivery were included. Indications included for operative delivery were: failure to descend, nonreassuring fetal status, labor dystocia, or maternal exhaustion. The primary outcomes included a composite neonatal outcome (death, fracture, length of stay ≥3 days beyond mother's, low Apgar, subgaleal hemorrhage, ventilator support, hypoxic encephalopathy, brachial plexus injury, facial nerve palsy) and individual maternal outcomes (postpartum hemorrhage, third- and fourth-degree tears [severe lacerations], and postpartum infection). Outcomes were examined by the 3 attempted modes of delivery. Odds ratios (OR) were calculated for primary outcomes adjusting for confounders. Final mode of delivery was quantified. Results In all, 2531 women met inclusion criteria. No difference in the neonatal composite outcome was observed between groups. Vacuum attempt was associated with the lowest frequency of maternal complications (postpartum infection 0.2% vs 0.9% forceps vs 5.3% cesarean, postpartum hemorrhage 1.4% vs 2.8% forceps vs 3.8% cesarean), except for severe lacerations (19.1% vs 33.8% forceps vs 0% cesarean). When confounders were taken into account, both forceps (OR, 0.16; 95% confidence interval, 0.05–0.49) and vacuum (OR, 0.04; 95% confidence interval, 0.01–0.17) were associated with a significantly lower odds of postpartum infection. The neonatal composite and postpartum hemorrhage were not significantly different between modes of attempted delivery. Cesarean occurred in 6.4% and 4.4% of attempted vacuum and forceps groups ( P = .04). Conclusion In patients needing second-stage delivery assistance with a station of +2 or below, attempted operative vaginal delivery was associated with a lower frequency of postpartum infection, but higher frequency of severe lacerations.

Use of androgenic anabolic steroids continues to be common in spite of widespread awareness of associated adverse effects and ethical concerns, with self-reported rates of anabolic steroid abuse as high as 15% in competitive adult athletes1. Overall, the highest rate of steroid abuse is suspected to be among recreational bodybuilders, with the primary goal of enhancing cosmetic appearance rather than improving performance2,3. A variety of complications associated with intramuscular injection of these commonly abused drugs, ranging from peripheral nerve palsy4,5 to atypical mycobacterial infection6, has been reported. Acute life-threatening complications, on the other hand, are exceedingly rare. We present a life-threatening case of clostridial myonecrosis resulting from intramuscular injection of contaminated anabolic steroids in a recreational bodybuilder. The patient was informed that data concerning this case would be submitted for publication, and he consented. A thirty-six-year-old otherwise healthy man presented to the emergency department thirty-six hours after intramuscular injection of anabolic steroids into the anterior aspect of the right thigh. He reported progressive right thigh pain and swelling, subjective fever and chills, and an inability to bear weight on the right lower extremity. On initial examination, he was nontoxic-appearing, afebrile, and hemodynamically stable but anxious about the rapidly declining condition of the lower extremity. The right thigh was markedly swollen with an enlarging area of ecchymosis centered at the injection site anterolaterally. The thigh was firm and tender to palpation, with crepitus from the inguinal crease to the knee. Initial laboratory abnormalities included …

Purpose To evaluate knee stability after anterior cruciate ligament (ACL) reconstruction using 2 modern clinically relevant single-bundle constructs. Methods Two arthroscopic ACL reconstructions were performed on 6 fresh-frozen human cadaveric knees using bone–patellar tendon–bone autografts. The tibial tunnel was centered in the anatomic tibial footprint. The femoral tunnel was reamed through the anteromedial (AM) portal and centered alternately in either the AM portion of the femoral footprint (center-AM) or the center of the femoral footprint (center-center). Two external loading conditions were applied: (1) a 134-N anterior tibial load and (2) a 10-Nm valgus load combined with a 5-Nm internal tibial torque. Resulting kinematics were determined under 4 conditions: (1) ACL intact, (2) ACL deficient, (3) center-AM reconstruction, and (4) center-center reconstruction. Results In response to anterior tibial loading, anterior translation was similar in the ACL-intact knee and the 2 reconstructions at 0° to 60° of flexion but was greater in the reconstructed specimens at 90°. In response to the complex rotatory load, internal tibial rotation (ITR) at 30° of flexion was slightly greater in center-AM knees compared with ACL-intact knees (11.0° ± 0.6° v 10.5° ± 0.6°, P = .03). At other angles tested, ITR in both reconstructions was similar to the ACL-intact knee ( P > .05). When we compared the 2 reconstruction alternatives, however, center-center knees exhibited greater resistance to ITR at all angles ( P Conclusion Anatomic single-bundle ACL reconstruction performed with the femoral tunnel placed through the AM portal restores translational and rotational knee stability to an extent that closely approximates the ACL-intact condition. When compared with the AM femoral tunnel position, a femoral tunnel positioned in the anatomic center of the femoral origin of the ACL may further improve rotatory stability without sacrificing anterior stability. Clinical Relevance This study provides additional biomechanical evidence in support of anatomic single-bundle ACL reconstruction with tunnels positioned in the center of the femoral and tibial footprints.

The human pathogen Mycobacterium tuberculosis (Mtb) encodes 20 cytochrome P450 (P450) enzymes. Gene essentiality for viability or host infection was demonstrated for Mtb P450s CYP128, CYP121 and CYP125. Structure/function studies on Mtb P450s revealed key roles contributing to bacterial virulence and persistence in the host. Various azole-class drugs bind with high affinity to the Mtb P450 heme and are potent Mtb antibiotics. This paper reviews the current understanding of the biochemistry of Mtb P450s, their interactions with azoles and their potential as novel Mtb drug targets. Mtb multidrug resistance is widespread and novel therapeutics are desperately needed. Simultaneous drug targeting of several Mtb P450s crucial to bacterial viability/persistence could offer a new route to effective antibiotics and minimize the development of drug resistance.

Efforts to assure high-quality, safe, clinical care depend upon capturing information about near-miss and adverse outcome events. Inconsistent or unreliable information capture, especially for infrequent events, compromises attempts to analyze events in quantitative terms, understand their implications, and assess corrective efforts. To enhance reporting, we developed a secure, electronic, mandatory system for reporting quality assurance data linked to our electronic anesthesia record.We used the capabilities of our anesthesia information management system (AIMS) in conjunction with internally developed, secure, intranet-based, Web application software. The application is implemented with a backend allowing robust data storage, retrieval, data analysis, and reporting capabilities. We customized a feature within the AIMS software to create a hard stop in the documentation workflow before the end of anesthesia care time stamp for every case. The software forces the anesthesia provider to access the separate quality assurance data collection program, which provides a checklist for targeted clinical events and a free text option. After completing the event collection program, the software automatically returns the clinician to the AIMS to finalize the anesthesia record.The number of events captured by the departmental quality assurance office increased by 92% (95% confidence interval [CI] 60.4%-130%) after system implementation. The major contributor to this increase was the new electronic system. This increase has been sustained over the initial 12 full months after implementation. Under our reporting criteria, the overall rate of clinical events reported by any method was 471 events out of 55,382 cases or 0.85% (95% CI 0.78% to 0.93%). The new system collected 67% of these events (95% confidence interval 63%-71%).We demonstrate the implementation in an academic anesthesia department of a secure clinical event reporting system linked to an AIMS. The system enforces entry of quality assurance information (either no clinical event or notification of a clinical event). System implementation resulted in capturing nearly twice the number of events at a relatively steady case load.

The Mycobacterium tuberculosis cytochrome P450 enzyme CYP142 is encoded in a large gene cluster involved in metabolism of host cholesterol. CYP142 was expressed and purified as a soluble, low spin P450 hemoprotein. CYP142 binds tightly to cholesterol and its oxidized derivative cholest-4-en-3-one, with extensive shift of the heme iron to the high spin state. High affinity for azole antibiotics was demonstrated, highlighting their therapeutic potential. CYP142 catalyzes either 27-hydroxylation of cholesterol/cholest-4-en-3-one or generates 5-cholestenoic acid/cholest-4-en-3-one-27-oic acid from these substrates by successive sterol oxidations, with the catalytic outcome dependent on the redox partner system used. The CYP142 crystal structure was solved to 1.6 Å, revealing a similar active site organization to the cholesterol-metabolizing M. tuberculosis CYP125, but having a near-identical organization of distal pocket residues to the branched fatty acid oxidizing M. tuberculosis CYP124. The cholesterol oxidizing activity of CYP142 provides an explanation for previous findings that ΔCYP125 strains of Mycobacterium bovis and M. bovis BCG cannot grow on cholesterol, because these strains have a defective CYP142 gene. CYP142 is revealed as a cholesterol 27-oxidase with likely roles in host response modulation and cholesterol metabolism.

Rapid laboratory methods provide optimal support for active surveillance efforts to screen for methicillin-resistant Staphylococcus aureus (MRSA). Most laboratories struggle to determine the optimal use of resources, considering options to balance cost, speed, and diagnostic accuracy. To assess the performance of common methods, the first comparison of MRSASelect agar (MS) and CHROMagar MRSA (CA), with and without broth enrichment followed by a 24-h subculture to MS, was performed. Results were compared to those of the Xpert MRSA assay. For direct culture methods, the agreement between MS and CA was 98.8%. At 18 h, direct MS identified 93% of all positive samples from direct culture and 84% of those identified by the Xpert MRSA. For Trypticase soy broth-enriched MS culture, incubated overnight and then subcultured for an additional 24 h, the agreement with Xpert MRSA was 96%. The agreement between direct MS and Xpert MRSA was 100% when semiquantitative culture revealed a bacterial density of 2+ or greater; however, discrepancies between culture and Xpert MRSA arose for MRSA bacterial densities of 1+ or less, indicating low density as a common cause of false-negative culture results. Since 1+ or less was established as the most common MRSA carrier state, broth enrichment or PCR may be critical for the identification of all MRSA carriers who may be reservoirs for transmission. In this active-surveillance convenience sample, the use of broth enrichment followed by subculture to MS offered a low-cost but sensitive method for MRSA screening, with performance similar to that of Xpert MRSA PCR.

The purpose of this study was to determine whether high flexion leads to improved benefits in patient satisfaction, perception, and function after total knee arthroplasty (TKA). Data were collected on 122 primary TKAs. Patients completed a Total Knee Function Questionnaire. Knees were classified as low (≤110°), mid (111°-130°), or high flexion (N130°). Correlation between knee flexion and satisfaction was not statistically significant. Increased knee flexion had a significant positive association with achievement of expectations, restoration of a "normal" knee, and functional improvement. In conclusion, although the degree of postoperative knee flexion did not affect patient satisfaction, it did influence fulfillment of expectations, functional ability, and knee perception. This suggests that increased knee flexion, particularly more than 130°, may lead to improved outcomes after TKA. Keywords: total knee arthroplasty, patient-derived outcomes, patient satisfaction, high flexion, function. © 2011 Elsevier Inc. All rights reserved.

Much is known about the potential consequences of prenatal alcohol exposure through data developed in animals and man. However, little attempt has been made to compare the human and animal literature with respect to qualitative and quantitative similarities and differences. To this end, a comparison was made between the effects reported in humans following moderate levels of alcohol exposure and the neurobehavioral effects detected using animal models. A good deal of congruence was found with respect to qualitative endpoints. General functional categories, such as deficits in learning, inhibition, attention, regulatory behaviors, and motor performance were reported to be affected in both animals and children. Quantitatively, although the dose required to produce an effect differs across species, the resultant circulating blood alcohol levels are quite similar. In addition, while compelling data are limited, the magnitude of the observed effects are generally dose-related for both humans and animals.

Background: Documentation of key times and events is required to obtain reimbursement for anesthesia services. The authors installed an information management system to improve record keeping and billing performance but found that a significant number of their records still could not be billed in a timely manner, and some records were never billed at all because they contained documentation errors. Methods: Computer software was developed that automatically examines electronic anesthetic records and alerts clinicians to documentation errors by alphanumeric page and email. The software’s efficacy was determined retrospectively by comparing billing performance before and after its implementation. Staff satisfaction with the software was assessed by survey. Results: After implementation of this software, the percentage of anesthetic records that could never be billed declined from 1.31% to 0.04%, and the median time to correct documentation errors decreased from 33 days to 3 days. The average time to release an anesthetic record to the billing service decreased from 3.0 0.1 days to 1.1 0.2 days. More than 90% of staff found the system to be helpful and easier to use than the previous manual process for error detection and notification. Conclusion: This system allowed the authors to reduce the median time to correct documentation errors and the number of anesthetic records that were never billed by at least an order of magnitude. The authors estimate that these improvements increased their department’s revenue by approximately $400,000 per year. TO obtain reimbursement for anesthesia services in the United States, clear and complete billing documentation is required. This documentation includes specific time and event elements relating to the preanesthetic evaluation, intraanesthetic management, and postanesthetic care. The absence of even a single element or the presence of a wrong element can lead to the rejection of a claim for services rendered. Therefore, it is important that anesthesia practices identify and correct such documentation errors on anesthesia records to maximize revenues. Beyond its primary importance for revenue generation, billing documentation can also provide valuable evidence of proper medical care. 1 Achieving the goal of clear and complete documentation in every anesthetic record is a challenge, particularly in settings where anesthesiologists simultaneously direct the care of multiple patients and their primary focus of attention is on patient care and teaching. The advent of computerized anesthesia information management systems (AIMS) provides opportunities to develop novel tools and solutions to persistent problems in anesthesia practice, especially those related to consistent task execution and completion. Recently, it has been demonstrated that computerized automatic process monitoring and automatic alerts yield clinically important improvements in outcomes when applied to medical orders. 2,3 This suggests that other aspects of the care process, including seemingly mundane tasks such as billing documentation, would benefit from this approach. In the beginning of 2003, our department transitioned from recording intraoperative patient data using pen and paper to using an AIMS (Saturn; Draeger, Telford, PA) for documentation. The primary purpose of this transition was to facilitate correct data capture, 4 to minimize recording errors, 5 and to reduce the cost and time associated with generating bills by simplifying the billing process. However, after the transition to this system, it was apparent that a significant number of our records could not be submitted for payment even months after the date of service because they contained deficiencies and errors related to documentation that precluded billing. We hypothesized that we could reduce documentation errors, improve billing performance, and capture lost revenue by developing software and instituting a computerized system that would automatically search electronic anesthetic records for documentation errors and alert anesthesia personnel in near real time. This report describes this system, its implementation, and its impact on our documentation and billing performance.

Primary fallopian tube carcinoma is a rare tumor. The aim of this study was to evaluate clinical characteristics and management of fallopian tube malignancies at a large tertiary care cancer institute.A retrospective review of the Tumor Registry was conducted to identify all primary fallopian tube carcinomas between 1980 and 2001. Medical charts were retrospectively reviewed. Primary endpoints were overall survival and disease recurrence.Thirty-five patients had histology consistent with fallopian tube carcinoma. The median age at diagnosis was 56 years. The most common signs or symptoms were abnormal vaginal bleeding (29%) and abdominal/pelvic mass (26%). The most common histology was adenocarcinoma in 16 (46%) patients. Five patients (14%) were Stage I, seven patients (20%) Stage II, 17 patients (49%) Stage III and six patients (17%) Stage IV. Thirty-two (91%) patients received adjuvant chemotherapy and 77% received platinum-based chemotherapy. Twenty-seven (77%) patients underwent second-look surgery, of which 17 patients (63%) were positive for disease. The 5-year survival rate was 64% for Stage I, 42% for Stage II, 32% for Stage III, and 17% for Stage IV.Fallopian tube malignancies are rare and carry a poor prognosis. More extensive research needs to be performed to have definitive etiologic, diagnostic and treatment guidelines.

Background Rolling circle amplification of ligated probes is a simple and sensitive means for genotyping directly from genomic DNA. SNPs and mutations are interrogated with open circle probes (OCP) that can be circularized by DNA ligase when the probe matches the genotype. An amplified detection signal is generated by exponential rolling circle amplification (ERCA) of the circularized probe. The low cost and scalability of ligation/ERCA genotyping makes it ideally suited for automated, high throughput methods. Results A retrospective study using human genomic DNA samples of known genotype was performed for four different clinically relevant mutations: Factor V Leiden, Factor II prothrombin, and two hemochromatosis mutations, C282Y and H63D. Greater than 99% accuracy was obtained genotyping genomic DNA samples from hundreds of different individuals. The combined process of ligation/ERCA was performed in a single tube and produced fluorescent signal directly from genomic DNA in less than an hour. In each assay, the probes for both normal and mutant alleles were combined in a single reaction. Multiple ERCA primers combined with a quenched-peptide nucleic acid (Q-PNA) fluorescent detection system greatly accellerated the appearance of signal. Probes designed with hairpin structures reduced misamplification. Genotyping accuracy was identical from either purified genomic DNA or genomic DNA generated using whole genome amplification (WGA). Fluorescent signal output was measured in real time and as an end point. Conclusions Combining the optimal elements for ligation/ERCA genotyping has resulted in a highly accurate single tube assay for genotyping directly from genomic DNA samples. Accuracy exceeded 99 % for four probe sets targeting clinically relevant mutations. No genotypes were called incorrectly using either genomic DNA or whole genome amplified sample.

Our goal in this study was to develop decision support systems for resident operating room (OR) assignments using anesthesia information management system (AIMS) records and Accreditation Council for Graduate Medical Education (ACGME) case logs and evaluate the implementations. We developed 2 Web-based systems: an ACGME case-log visualization tool, and Residents Helping in Navigating OR Scheduling (Rhinos), an interactive system that solicits OR assignment requests from residents and creates resident profiles. Resident profiles are snapshots of the cases and procedures each resident has done and were derived from AIMS records and ACGME case logs. A Rhinos pilot was performed for 6 weeks on 2 clinical services. One hundred sixty-five requests were entered and used in OR assignment decisions by a single attending anesthesiologist. Each request consisted of a rank ordered list of up to 3 ORs. Residents had access to detailed information about these cases including surgeon and patient name, age, procedure type, and admission status. Success rates at matching resident requests were determined by comparing requests with AIMS records. Of the 165 requests, 87 first-choice matches (52.7%), 27 second-choice matches (16.4%), and 8 third-choice matches (4.8%) were made. Forty-three requests were unmatched (26.1%). Thirty-nine first-choice requests overlapped (23.6%). Full implementation followed on 8 clinical services for 8 weeks. Seven hundred fifty-four requests were reviewed by 15 attending anesthesiologists, with 339 first-choice matches (45.0%), 122 second-choice matches (16.2%), 55 third-choice matches (7.3%), and 238 unmatched (31.5%). There were 279 overlapping first-choice requests (37.0%). The overall combined match success rate was 69.4%. Separately, we developed an ACGME case-log visualization tool that allows individual resident experiences to be compared against case minimums as well as resident peer groups. We conclude that it is feasible to use ACGME case-log data in decision support systems for informing resident OR assignments. Additional analysis will be necessary to assess the educational impact of these systems.

PCOS is a common disorder of unknown etiology. Studies of first-degree relatives of women diagnosed with PCOS suggest familial clustering of the disease. A prospective study of first-degree female relatives of women with PCOS conducted by NCPIR found that 46% of ascertainable sisters of women with PCOS were hyperandrogenemic. NCPIR has conducted linkage and association studies using affected sibling-pair analysis and the transmission/disequilibrium test to explore candidate PCOS genes. These studies point a finger at a region 1 MB centromeric to the insulin receptor gene on chromosome 19.

Understanding how viral components collaborate to convert the human immunodeficiency virus type 1 genome from single-stranded RNA into double-stranded DNA is critical to the understanding of viral replication. Not only must the correct reactions be carried out, but unwanted side reactions must be avoided. After minus-strand strong stop DNA (−sssDNA) synthesis, degradation of the RNA template by the RNase H domain of reverse transcriptase (RT) produces single-stranded DNA that has the potential to self-prime at the imperfectly base-paired TAR hairpin, making continued DNA synthesis impossible. Although nucleocapsid protein (NC) interferes with −sssDNA self-priming in reverse transcription reactions in vitro, NC alone did not prevent self-priming of a synthetic −sssDNA oligomer. NC did not influence DNA bending and therefore cannot inhibit self-priming at hairpins by directly blocking hairpin formation. Using DNA oligomers as a model for genomic RNA fragments, we found that a 17-base DNA fragment annealed to the 3′ end of the −sssDNA prevented self-priming in the presence of NC. This implies that to avoid self-priming, an RNA-DNA hybrid that is more thermodynamically stable than the hairpin must remain within the hairpin region. This suggests that NC prevents self-priming by generating or stabilizing a thermodynamically favored RNA-DNA heteroduplex instead of the kinetically favored TAR hairpin. In support of this idea, sequence changes that increased base pairing in the DNA TAR hairpin resulted in an increase in self-priming in vitro. We present a model describing the role of NC-dependent inhibition of self-priming in first-strand transfer.

The incidence of malignant melanoma is increasing. Because of increased awareness, early recognition of malignant melanoma has become more common. In 1997, a new staging system for cutaneous melanoma was proposed, with reclassification of thin melanoma1 mm, with and without ulceration. This report evaluates the pathologic and clinical features of thin melanomas influencing recurrence and survival from a tertiary cancer center in an attempt to correlate findings with the proposed staging system. A review of the Roswell Park Cancer Institute tumor registry identified 352 patients with thin cutaneous melanomas (1.0 mm) seen during an 18-year period ending August 30, 1998. Overall survival was 93 and 87 per cent at 5 and 10 years, respectively. Disease-free survival was 94 and 93 per cent at 5 and 10 years, respectively. Local recurrence occurred in 3 per cent of patients, regional recurrence in 3 per cent, and metastatic disease in 3 per cent, for an overall recurrence of 7 per cent, with a median follow-up of 118 months. Only the presence of ulceration was a significant prognostic factor for recurrence by both univariate and multivariate analysis. Failure rates (any recurrence) by Clark levels I, II, and III/IV were 3, 5, and 10 per cent, respectively (P = 0.14). Failure rates by tumor thickness (mm), for 0.0-0.24, 0.25-0.49, 0.50-0.74, and 0.75-0.99 were 3, 4, 7, and 10 per cent, respectively (P = 0.49). Ten-year disease-free survival for ulceration versus no ulceration was 40 and 94 per cent, respectively (P0.0001). We conclude that thin cutaneous melanoma carries an excellent prognosis with appropriate treatment. Our findings support inclusion of ulceration in a new staging system. Lesions 0.76 to 0.99 mm and Clark level III and IV may warrant close observation as a separate subgroup.

Estrogen-inducible genes contain an enhancer called the estrogen response element (ERE), a double-stranded inverted repeat. The estrogen receptor (ER) is generally thought to bind to the double-stranded ERE. However, some reports provide evidence that an ER homodimer can bind a single strand of the ERE and suggest that single-stranded ERE binding is the preferred binding mode for ER. Since these two models describe quite different mechanisms of receptor action, we have attempted to reconcile the observations. Analyzing DNA structure by nuclease sensitivity, we found that two identical molecules of a single strand of DNA containing the ERE sequence can partially anneal in an antiparallel manner. Bimolecular annealing produces double-stranded inverted repeats, with adjacent unannealed tails. The amount of annealing correlates exactly with the ability of ER to bind bimolecular EREs. Either strand of an ERE could anneal to itself in a way that would bind ER. We conclude that ER binds only the annealed double-stranded ERE both in vitro and in vivo.

Because of its role in cell motility and growth regulation, gelsolin, an actin-binding protein, has been considered a tumor suppressor and a potential prognostic marker in some neoplasias, such as breast and bladder cancer. Little is known about its immunoexpression in prostatic adenocarcinoma (PCA).Formalin-fixed, paraffin-embedded tissues of 72 prostatectomy specimens with adenocarcinoma and 8 nonneoplastic prostates from autopsies were stained with a gelsolin monoclonal antibody using the Avidin-biotin-peroxidase complex (ABC) method after microwave antigen retrieval. Immunoreactivity was evaluated in PCA, prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), and nonproliferative glandular tissue and stroma. The results were statistically analyzed.Consistent gelsolin immunoreactivity was seen in prostatic stromal cells, smooth muscle, endothelia, and nerves. Variable gelsolin expression was seen in 20-100% (average (A) = 65.5%) of glandular cells in nonproliferative tissue (N = 75); 0-50% (A = 9.7%) in BPH (N = 59); 0-80% (A = 8.9%) in PIN (N = 61); and 0-90% (A = 9.3%) in PCA (N = 71). The level of gelsolin expression in nonproliferative prostatic tissue was similar between prostates with PCA (A = 63.4%) and nonneoplastic prostates (A = 67.5%). The level of gelsolin expression did not correlate with age, tumor size, Gleason score, or stage.Gelsolin is decreased in PCA, PIN, and BPH in comparison to nonproliferative tissue. The role of this downregulation in the development of PCA is not clear. The similar reduction seen in PIN and BPH suggests that this event takes place indiscriminately in hyperplasia and early tumorigenesis in the prostate, which might limit its prognostic significance in PCA.

There are technical difficulties in resecting soft tissue sarcomas extending to or crossing a joint. The objective of this study was to determine the rate of amputation and local recurrence rate for these sarcomas and compare them with the respective rates for overall extremity sarcomas.Retrospective review of 78 patients with sarcoma near a joint compared with 215 patients with extremity sarcomas accrued during the same period, 1977-1994. Of these 78 patients, 64 were in the lower and 14 in the upper extremity. Most common histologic subtypes were malignant fibrous histiocytoma (15/78, 19%), synovial sarcoma (11/78, 14%), liposarcoma (11/78, 14%), and leiomyosarcoma (10/78, 13%). The surgical treatment consisted of local excision in 10 (13%), wide excision in 56 (72%), and amputation in 12 (15%). Adjuvant radiation was given to 26 patients.Local recurrence was noted in 20% (16/78) patients. The incidence of local recurrence in the surgery alone group (n = 52) was 15% (8/52) and in the surgery plus adjuvant radiation group (n = 26) it was 31% (8/26); P = 0.11. Of the 16 patients with local recurrence, 9 (56%) required amputation. The 5-year and 10-year survival rates for the entire group of patients were 68% and 60% respectively. On multivariate analysis survival varied according to grade (P = 0.05) and tumor size (P = 0.02).Amputation was finally required in 27% (21/78) for local control of the disease. The local recurrence rate was 20%. These rates appear to be somewhat higher than those reported in our overall extremity sarcoma series and those in most modern series of overall extremity sarcomas, but the 5- and 10-year survival rates are similar to those of the latter.

Two infants with chromosome 22q11 deletion syndrome were noted to have symmetrically enlarged Sylvian fissures on cranial MRI. We compared the size of the Sylvian fissures in neuroimaging studies from 17 other subjects with del 22q11 to age-matched disease controls. The mean anterior interopercular distance was used as an index of Sylvian fissure enlargement. Symmetric enlargement of the Sylvian fissures was present in 10 of 17 subjects with del 22q11. The age-incidence pattern, as well as follow-up scans in 2 patients, suggests delayed growth of the opercular region in these patients. Subjects with del 22q11 consistently had disproportionate enlargement of the left Sylvian fissure compared to the right. This observation suggests that a gene (or genes) in the deleted region affects the development of the left and right perisylvian cortex in different ways. Abnormal development of the operculum may explain some of the neurodevelopmental features that are common among individuals with 22q11 deletion syndrome.

Patients with squamous cell carcinoma (SCC) of the skin may exhibit locally advanced or metastatic disease and present a challenging management problem.A retrospective review of 40 patients with advanced SCC of the trunk or extremity managed at Roswell Park Cancer Institute from 1982 through 1992 was performed to identify clinical and pathologic factors that influenced outcome.There were 27 males and 13 females with a median age of 61 years. Median follow-up was 24 months. Surgical resection to control the primary tumor was often extensive. Amputation was required in nine patients, hemipelvectomy in three patients, and hemicorporectomy in one patient. Median survival was 28 months, and 5-year survival was 43%. Univariate analysis identified stage (P = 0.04), size (P = 0.0001), type of surgical procedure (P = 0.009), and margins of resection (P = 0.005) as having prognostic significance. On multivariate analysis, stage (P = 0.04) and size (P = 0.02) were found to be significant.Optimum treatment for advanced SCC of the trunk and extremity involves surgical resection with uninvolved margins. The role of elective node dissection remains undefined. Investigation is needed to define the role of neoadjuvant therapy that may improve functional and cosmetic results.