Expanding Glycomic Investigations through Thiol-Derivatized Glycans.

N-(2-thioethyl)-2-aminobenzamide (TEAB), a novel glycan auxiliary, was synthesized and its utility was evaluated. The auxiliary was conjugated to glycans by reductive amination with the water-stable reagent 2-picoline borane complex. Glycan products, which ranged from 1 to 7 linked hexoses, were all isolated in yields ranging from 60% to 90% after purification by reverse-phase chromatography. The novel conjugate introduces a convenient, shelf-stable thiol directly onto the desired free glycans with purification advantages and direct modification with efficient reactions through alkenes, halides, epoxides, disulfides, and carboxylates in yields of 49% to 93%. Subsequently, a thiol-selective modification of the BSA protein was used to generate a neoglycoprotein with a bifunctional PEG-maleimide linker. To further illustrate the utility of a thiol motif, 2-thiopyridine activation of a thiol-containing support facilitated the covalent chromatographic purification of labeled glycans in yields up to 63%. Finally, initial proof of concept of implementation in a light printed microarray was explored and validated through FITC-labeled concanavalin A binding. In conclusion, the thiol-functionalized glycans produced greatly expand the diversity of bioconjugation tools that can be developed with glycans and enable a variety of biological investigations.

FIRSTT study: randomized controlled trial of uterine artery embolization vs focused ultrasound surgery.

BACKGROUND: Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE: The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN: The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS: From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION: Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER: NCT00995878, clinicaltrials.gov.

Periprocedural outcomes comparing fibroid embolization and focused ultrasound: a randomized controlled trial and comprehensive cohort analysis.

BACKGROUND: Uterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. OBJECTIVE: The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. RESULTS: Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P <.001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self-rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median [interquartile range], 5 [1-7] vs 1 [1-4]; P = .002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < .001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < .001) and to have a longer median (interquartile range) recovery time (days off work, 8 [6-14] vs 4 [2-7]; P < .001; days until return to normal, 15 [10-29] vs 10 [10-15]; P = .02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities (P < .001 for each). Results were similar when restricted to the randomized controlled trial. CONCLUSION: Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.

Fibroid interventions: reducing symptoms today and tomorrow: extending generalizability by using a comprehensive cohort design with a randomized controlled trial.

BACKGROUND: Uterine fibroids are an important source of morbidity for reproductive-aged women. Despite an increasing number of alternatives, hysterectomies account for about 75% of all fibroid interventional treatments. Evidence is lacking to help women and their health care providers decide among alternatives to hysterectomy. Fibroid Interventions: Reducing Symptoms Today and Tomorrow (NCT00995878, clinicaltrials.gov) is a randomized controlled trial to compare the safety, efficacy, and economics of 2 minimally invasive alternatives to hysterectomy: uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery. Although randomized trials provide the highest level of evidence, they have been difficult to conduct in the United States for interventional fibroid treatments. Thus, contemporaneously recruiting women declining randomization may have value as an alternative strategy for comparative effectiveness research. OBJECTIVE: We sought to compare baseline characteristics of randomized participants with nonrandomized participants meeting the same enrollment criteria and to determine whether combining the 2 cohorts in a comprehensive cohort design would be useful for analysis. STUDY DESIGN: Premenopausal women with symptomatic uterine fibroids seeking interventional therapy at 3 US academic medical centers were randomized (1:1) in 2 strata based on calculated uterine volume (<700 and ≥700 cc(3)) to undergo embolization or focused ultrasound surgery. Women who met the same inclusion criteria but declined randomization were offered enrollment in a parallel cohort. Both cohorts were followed up for a maximum of 36 months after treatment. The measures addressed in this report were baseline demographics, symptoms, fibroid and uterine characteristics, and scores on validated quality-of-life measures. RESULTS: Of 723 women screened, 57 were randomized and 49 underwent treatment (27 with focused ultrasound and 22 with embolization). Seven of the 8 women randomized but not treated were assigned to embolization. Of 34 women in the parallel cohort, 16 elected focused ultrasound and 18 elected embolization. Compared with nonrandomized participants, randomized participants had higher mean body mass index (28.7 vs 25.3 kg/m(2); P = .01) and were more likely to be gravid (77% vs 47%; P = .003) and smokers (42% vs 12%; P = .003). Age, race, uterine volume, number of fibroids, and baseline validated measures of general and disease-specific quality of life, pain, depression, and sexual function did not differ between the groups. When we performed a comprehensive cohort analysis and analyzed by treatment arm, the only baseline difference observed was a higher median McGill Pain Score among women undergoing focused ultrasound (10.5 vs 6; P = .03); a similar but nonsignificant trend was seen in visual analog scale scores for pain (median, 39.0 vs 24.0; P = .06). CONCLUSION: Using a comprehensive cohort analysis of study data could result in additional power and greater generalizability if results are adjusted for baseline differences.

Association of maternal IL-1 receptor antagonist intron 2 gene polymorphism and preterm birth.

OBJECTIVE: This study was undertaken to determine whether the interleukin-1 receptor antagonist (IL-1RN) variable number tandem repeat polymorphism is associated with preterm birth. STUDY DESIGN: A case-control study was performed. Cases (n = 95) delivered before 37 weeks after preterm labor (PTL) or preterm premature rupture of membranes (PPROM) and controls (n = 105) delivered after 37 weeks. Maternal DNA was genotyped by polymerase chain reaction for a length polymorphism in intron 2 of the IL-1RN gene. RESULTS: There was no significant difference in maternal age, ethnicity, insurance status, or parity between groups. Allele and genotype frequencies did not differ significantly from that expected under Hardy-Weinberg equilibrium (P = .59) in the total group as well as study groups. Of the 95 cases, 26.8% had at least 1 copy of allele 2 present compared with 12.4% in the control group (P < .0004). CONCLUSION: Maternal carriage of at least 1 copy of the IL-1RN allele 2 appears to be associated with increased risk of preterm birth.

Mortalidad y factores sociales del cáncer de próstata para la gestión de políticas públicas. Veracruz, México / Mortality and social factors of prostate cancer for public policy management. Veracruz, Mexic / Mortalidade e factores sociais do cancro da próstata para a gestão de políticas públicas. Veracruz, México

Introducción: las elevadas tasas de mortalidad por cáncer de próstata en Veracruz indican la necesidad de gestionar políticas públicas equitativas para su control. Por ello, es necesario analizar las tendencias de mortalidad y los factores sociales relacionados con la salud de la población. Métodos: cálculo de las tasas de mortalidad a nivel nacional y estatal por edad, y en Veracruz, por regiones económicas; en relación con su grado de rezago social. Resultados: La tasa de mortalidad por cáncer de próstata en Veracruz es mayor que la tasa nacional. Dentro del estado, la región del Papaloapan presentó la mayor mortalidad, y un grado de rezago social medio.

Introduction: the high mortality rates due to prostate cancer in Veracruz indicate the need to manage equitable public policies for its control. Therefore, it is necessary to analyze mortality trends and social factors related to population health. Methods: Calculation of mortality rates at national and state level by age, and in Veracruz, by economic regions; in relation to their degree of social backwardness. Results: The mortality rate for prostate cancer in Veracruz is higher than the national rate. Within the state, the Papaloapan region presented the highest mortality and a medium degree of social backwardness.

Introdução: As elevadas taxas de mortalidade por cancro da próstata em Veracruz indicam a necessidade de políticas públicas equitativas para controlar o cancro da próstata. Por isso, é necessário analisar as tendências de mortalidade e os fatores sociais relacionados à saúde da população. Métodos: Cálculo das taxas de mortalidade a nível nacional e estadual, por idade, e em Veracruz, por regiões económicas, em relação ao seu grau de atraso social. Resultados: A taxa de mortalidade por cancro da próstata em Veracruz é superior à taxa nacional. Dentro do estado, a região de Papaloapan apresentou a maior mortalidade e um grau médio de atraso social.

Mortalidad y factores sociales del cáncer de próstata para la gestión de políticas públicas. veracruz, méxico

Introducción: Las elevadas tasas de mortalidad por cáncer de próstata en Veracruz indican la necesidad de gestionar políticas públicas equitativas para su control. Por ello, es necesario analizar las tendencias de mortalidad y los factores sociales relacionados con la salud de la población. Métodos: Cálculo de las tasas de mortalidad a nivel nacional y estatal por edad, y en Veracruz, por regiones económicas; en relación con su grado de rezago social. Resultados: La tasa de mortalidad por cáncer de próstata en Veracruz es mayor que la tasa nacional. Dentro del estado, la región del Papaloapan presentó la mayor mortalidad, y un grado de rezago social medio. Conclusiones: De acuerdo con los datos analizados, las regiones con las tasas más altas de mortalidad en Veracruz no corresponden a las regiones con alto grado de rezago social.

Introduction: The high rates of mortality caused by prostate cancer in Veracruz indicate the need to manage equitable public policies for its control. For this reason, it is necessary to analyze mortality trends and social factors related to population health. Methods: Calculation of mortality rates at national-state level, by age; and for Veracruz, by economic regions; in relation to its degree of social lag. Results: The mortality rate of prostate cancer in Veracruz is higher than the national rate. Within the state, the Papaloapan region presented the highest mortality, and an average degree of social lag. Conclusions: In Veracruz, according to the data analyzed, the regions with the highest mortality rates do not correspond to regions with a high degree of social lag.

Introdução: As altas taxas de mortalidade por câncer de próstata em Veracruz indicam a necessidade de gerenciar políticas públicas equitativas para seu controle. Para isso, é necessário analisar tendências de mortalidade e fatores sociais relacionados à saúde da população. Métodos: Cálculo das taxas de mortalidade a nível nacional e estatal, por idade; e para Veracruz, por regiões econômicas; em relação ao seu grau de atraso social. Resultados: A taxa de mortalidade por câncer de próstata em Veracruz é superior à taxa nacional. Dentro do estado, a região de Papaloapan apresentou a maior mortalidade e um grau de atraso social médio. Conclusões: De acordo com os dados analisados, em Veracruz, as regiões com maiores taxas de mortalidade não correspondem a regiões com alto grau de atraso social.

The morbidity and mortality conference: a unique opportunity for teaching empathic communication.

BACKGROUND: The morbidity and mortality conference is an educational tradition in American medicine that dates to the early 20th century. Traditionally, this conference has focused entirely on issues of diagnosis and treatment, in the context of a disappointing clinical outcome. INTERVENTION: We report on a new method for teaching empathic doctor-patient communication skills at an obstetrics and gynecology morbidity and mortality conference. For each case presented, we identified the communications challenges and allowed faculty and residents to "practice" the discussion they would have with the patient and the patient's family in that situation. In some sessions, actors assumed the role of the patient. Following the discussion of the case, we offered didactic presentations on how we communicate with patients and their families. These focused on techniques for being patient centered and included the use of body language, open-ended questioning, reflective listening before offering to explain, and the importance of naming and validating emotions. RESULTS: The majority of participants felt the sessions to be helpful, and after one month many were able to identify a positive change in their interactions with patients. CONCLUSIONS: We believe that this unique teaching format allows learners to refine their communication skills in the context of situations that they know to be both realistic and important.