Status of Women in Academic Anesthesiology: A 10-Year Update.

BACKGROUND: Gender inequity is still prevalent in today's medical workforce. Previous studies have investigated the status of women in academic anesthesiology. The objective of this study is to provide a current update on the status of women in academic anesthesiology. We hypothesized that while the number of women in academic anesthesiology has increased in the past 10 years, major gender disparities continue to persist, most notably in leadership roles. METHODS: Medical student, resident, and faculty data were obtained from the Association of American Medical Colleges. The number of women in anesthesiology at the resident and faculty level, the distribution of faculty academic rank, and the number of women chairpersons were compared across the period from 2006 to 2016. The gender distribution of major anesthesiology journal editorial boards and data on anesthesiology research grant awards, among other leadership roles, were collected from websites and compared to data from 2005 and 2006. RESULTS: The number (%) of women anesthesiology residents/faculty has increased from 1570 (32%)/1783 (29%) in 2006 to 2145 (35%)/2945 (36%) in 2016 (P = .004 and P < .001, respectively). Since 2006, the odds that an anesthesiology faculty member was a woman increased approximately 2% per year, with an estimated odds ratio of 1.02 (95% confidence interval, 1.014-1.025; P < .001). In 2015, the percentage of women anesthesiology full professors (7.4%) was less than men full professors (17.3%) (difference, -9.9%; 95% confidence interval of the difference, -8.5% to -11.3%; P < .001). The percentage of women anesthesiology department chairs remained unchanged from 2006 to 2016 (12.7% vs 14.0%) (P = .75). To date, neither Anesthesia & Analgesia nor Anesthesiology has had a woman Editor-in-Chief. The percentage of major research grant awards to women has increased significantly from 21.1% in 1997-2007 to 31.5% in 2007-2016 (P = .02). CONCLUSIONS: Gender disparities continue to exist at the upper levels of leadership in academic anesthesiology, most importantly in the roles of full professor, department chair, and journal editors. However, there are some indications that women may be on the path to leadership parity, most notably, the growth of women in anesthesiology residencies and faculty positions and increases in major research grants awarded to women.

Effect of Epidural Infusion Bolus Delivery Rate on the Duration of Labor Analgesia: A Randomized Clinical Trial.

BACKGROUND: Programmed intermittent boluses of local anesthetic have been shown to be superior to continuous infusions for maintenance of labor analgesia. High-rate epidural boluses increase delivery pressure at the catheter orifice and may improve drug distribution in the epidural space. We hypothesized that high-rate drug delivery would improve labor analgesia and reduce the requirement for provider-administered supplemental boluses for breakthrough pain. METHODS: Nulliparous women with a singleton pregnancy at a cervical dilation of less than or equal to 5 cm at request for neuraxial analgesia were eligible for this superiority-design, double-blind, randomized controlled trial. Neuraxial analgesia was initiated with intrathecal fentanyl 25 µg. The maintenance epidural solution was bupivacaine 0.625 mg/ml with fentanyl 1.95 µg/ml. Programmed (every 60 min) intermittent boluses (10 ml) and patient controlled bolus (5 ml bolus, lockout interval: 10 min) were administered at a rate of 100 ml/h (low-rate) or 300 ml/h (high-rate). The primary outcome was percentage of patients requiring provider-administered supplemental bolus analgesia. RESULTS: One hundred eight women were randomized to the low- and 102 to the high-rate group. Provider-administered supplemental bolus doses were requested by 44 of 108 (40.7%) in the low- and 37 of 102 (36.3%) in the high-rate group (difference -4.4%; 95% CI of the difference, -18.5 to 9.1%; P = 0.67). Patient requested/delivered epidural bolus ratio and the hourly bupivacaine consumption were not different between groups. No subject had an adverse event. CONCLUSIONS: Labor analgesia quality, assessed by need for provider- and patient-administered supplemental analgesia and hourly bupivacaine consumption was not improved by high-rate epidural bolus administration.

A herpes simplex virus 2 glycoprotein D mutant generated by bacterial artificial chromosome mutagenesis is severely impaired for infecting neuronal cells and infects only Vero cells expressing exogenous HVEM.

We constructed a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome (BAC) clone, bHSV2-BAC38, which contains full-length HSV-2 inserted into a BAC vector. Unlike previously reported HSV-2 BAC clones, the virus genome inserted into this BAC clone has no known gene disruptions. Virus derived from the BAC clone had a wild-type phenotype for growth in vitro and for acute infection, latency, and reactivation in mice. HVEM, expressed on epithelial cells and lymphocytes, and nectin-1, expressed on neurons and epithelial cells, are the two principal receptors used by HSV to enter cells. We used the HSV-2 BAC clone to construct an HSV-2 glycoprotein D mutant (HSV2-gD27) with point mutations in amino acids 215, 222, and 223, which are critical for the interaction of gD with nectin-1. HSV2-gD27 infected cells expressing HVEM, including a human epithelial cell line. However, the virus lost the ability to infect cells expressing only nectin-1, including neuronal cell lines, and did not infect ganglia in mice. Surprisingly, we found that HSV2-gD27 could not infect Vero cells unless we transduced the cells with a retrovirus expressing HVEM. High-level expression of HVEM in Vero cells also resulted in increased syncytia and enhanced cell-to-cell spread in cells infected with wild-type HSV-2. The inability of the HSV2-gD27 mutant to infect neuronal cells in vitro or sensory ganglia in mice after intramuscular inoculation suggests that this HSV-2 mutant might be an attractive candidate for a live attenuated HSV-2 vaccine.

Overexpression of inducible 70-kDa heat shock protein in mouse improves structural and functional recovery of skeletal muscles from atrophy.

Heat shock proteins play a key regulatory role in cellular defense. To investigate the role of the inducible 70-kDa heat shock protein (HSP70) in skeletal muscle atrophy and subsequent recovery, soleus (SOL) and extensor digitorum longus (EDL) muscles from overexpressing HSP70 transgenic mice were immobilized for 7 days and subsequently released from immobilization and evaluated after 7 days. Histological analysis showed that there was a decrease in cross-sectional area of type II myofiber from EDL and types I and II myofiber from SOL muscles at 7-day immobilization in both wild-type and HSP70 mice. At 7-day recovery, EDL and SOL myofibers from HSP70 mice, but not from wild-type mice, recovered their size. Muscle tetanic contraction decreased only in SOL muscles from wild-type mice at both 7-day immobilization and 7-day recovery; however, it was unaltered in the respective groups from HSP70 mice. Although no effect in a fatigue protocol was observed among groups, we noticed a better contractile performance of EDL muscles from overexpressing HSP70 groups as compared to their matched wild-type groups. The number of NCAM positive-satellite cells reduced after immobilization and recovery in both EDL and SOL muscles from wild-type mice, but it was unchanged in the muscles from HSP70 mice. These results suggest that HSP70 improves structural and functional recovery of skeletal muscle after disuse atrophy, and this effect might be associated with preservation of satellite cell amount.

Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.

Fatal Zika virus infection in the Americas: A systematic review.

INTRODUCTION: While death due to Zika virus (ZIKV) infection has been described, reports of fatal cases have been infrequent and no systematic reviews on the subject have been published. METHODS: A systematic review of the literature in four databases was performed to assess fatal outcomes of postnatal ZIKV infection and the available evidence that links ZIKV infection to death. RESULTS: Three hundred and eleven articles were retrieved; 20 of them were epidemiological reports from surveillance agencies and ministries of health. After screening by abstract and title, 59 articles were selected for full-text assessment. Of these, 35 were excluded (with reasons) and 24 were finally included for qualitative analysis. A total of 51 reported deaths associated with ZIKV infection in nine countries were identified. The majority of cases (56.9%) were not related to Guillain-Barré syndrome. Cases from three countries accounted for 67.6% of the deaths. ZIKV infection was laboratory-confirmed in the majority of cases (64.7%). DISCUSSION: ZIKV was not considered to be a dangerous, and much less a lethal pathogen, until very recently. However, an increasing number of fatalities have been published in the literature since the first death was reported in 2016. Additional research is needed to elucidate factors that may mediate the pathogenesis of severe, atypical, and fatal disease.

Mapping the residual incidence of taeniasis and cysticercosis in Colombia, 2009-2013, using geographical information systems: Implications for public health and travel medicine.

BACKGROUND: In Colombia, taeniasis and cysticercosis have been significantly reduced over the past decades, however still reported with implications for public health and travel medicine. METHODS: An observational, retrospective study, in which the incidence of taeniasis and cysticercosis (ICD-10 codes B68s/B69s) in Colombia, 2009-2013, was estimated based on data extracted from the Individual Health Records System (Registro Individual de Prestación de Servicios, RIPS) was performed. The Geographic Information System (GIS) generated national maps showing the distribution of taeniasis and cysticercosis by department by year. RESULTS: During the period, 3626 cases were reported (median 796/year), for a cumulative crude national rate of 7.7 cases/100,000pop; 58.2% corresponded to male; 57% were <40 year-old (10.2% < 9.9 year-old). Cases were 57.6% neurocysticercosis, the rest were taeniasis due to T. solium, T. saginata, ocular cysticercosis and cysticerci in other organs. Bolivar, a touristic department, had the highest cumulated incidence rate (16.17 cases/100,000pop), as also evident across the map series developed in this study. CONCLUSION: Despite the limitations of this study, data presented provide recent estimates of national taeniasis and cysticercosis incidence in the country useful in public health and for travel medicine practitioners, as some highly touristic areas presented higher disease incidence. Improved control, particularly of taeniasis, should be an attainable goal, which among other strategies would require improved sanitation and health education to prevent transmission, but also enhanced surveillance.

Influence of socio-economic inequality measured by the Gini coefficient on meningitis incidence caused by Mycobacterium tuberculosis and Haemophilus influenzae in Colombia, 2008-2011.

Bacterial meningitis is an important cause of infectious neurological morbidity and mortality. Its incidence has decreased with the introduction of vaccination programmes against preventable agents. However, low-income and middle-income countries with poor access to health care still have a significant burden of the disease. Thus, the relationship between the Gini coefficient and H. influenzae and M. tuberculosis meningitis incidence in Colombia, during 2008-2011, was assessed. In this ecological study, the Gini coefficient was obtained from the Colombian Department of Statistics, incidence rates were calculated (cases/1,000,000 pop) and linear regressions were performed using the Gini coefficient, to assess the relationship between the latter and the incidence of meningitis. It was observed that when inequality increases in the Colombian departments, the incidence of meningitis also increases, with a significant association in the models (p<0.01) for both M. tuberculosis (r²=0.2382; p<0.001) and H. influenzae (r²=0.2509; p<0.001). This research suggests that high Gini coefficient values influence the incidence of Mycobacterium tuberculosis and Haemophilus influenzae meningitis, showing that social inequality is critical to disease occurrence. Early detection, supervised treatment, vaccination coverage, access to health care are efficient control strategies.

Post-chikungunya chronic inflammatory rheumatism: results from a retrospective follow-up study of 283 adult and child cases in La Virginia, Risaralda, Colombia.

OBJECTIVE: There are limited studies in Latin America regarding the chronic consequences of the Chikungunya virus (CHIK), such as post-CHIK chronic inflammatory rheumatism (pCHIK-CIR). We assessed the largest cohort so far of pCHIK-CIR in Latin America, at the municipality of La Virginia, Risaralda, a new endemic area of CHIK in Colombia. METHODS: We conducted a cohort retrospective study in Colombia of 283 patients diagnosed with CHIK that persisted with pCHIK-CIR after a minimum of 6 weeks and up to a maximum of 26.1 weeks. pCHIK cases were identified according to validated criteria via telephone. RESULTS: Of the total CHIK-infected subjects, 152 (53.7%) reported persistent rheumatological symptoms (pCHIK-CIR). All of these patients reported joint pains (chronic polyarthralgia, pCHIK-CPA), 49.5% morning stiffness, 40.6% joint edema, and 16.6% joint redness. Of all patients, 19.4% required and attended for care prior to the current study assessment (1.4% consulting rheumatologists). Significant differences in the frequency were observed according to age groups and gender. Patients aged >40 years old required more medical attention (39.5%) than those ≤40 years-old (12.1%) (RR=4.748, 95%CI 2.550-8.840). CONCLUSIONS: According to our results, at least half of the patients with CHIK developed chronic rheumatologic sequelae, and from those with pCHIK-CPA, nearly half presented clinical symptoms consistent with inflammatory forms of the disease. These results support previous estimates obtained from pooled data of studies in La Reunion (France) and India and are consistent with the results published previously from other Colombian cohorts in Venadillo (Tolima) and Since (Sucre).

Factores pronósticos para pérdida de extremidad con trauma arterial periférico en un hospital de Colombia / Prognostic factors for extreme loss in peripheral arterial trauma at a Colombian hospital

INTRODUCCIÓN: El trauma vascular es un evento de baja frecuencia, con alta morbimortalidad que afecta la población joven; requiere en general un manejo quirúrgico. Se asocia a complicaciones desde la reintervención quirúrgica hasta la amputación de la extremidad, influenciado por variables tanto asociadas al trauma como a la atención hospitalaria. OBJETIVO: Determinar los factores de riesgo relacionados con amputación, en pacientes con trauma arterial periférico (TAP), atendidos en un Hospital de III nivel Huila- Colombia entre 2014-2017. MATERIALES Y MÉTODOS: Estudio observacional, analítico de corte retrospectiva con pacientes mayores de 13 años con TAP. RESULTADOS: Se incluyeron 79 pacientes, con un 1,56% de las consultas en nuestro Servicio de Urgencia. 89% hombres, promedio de edad 28,5 años. La principal comorbilidad fue la farmacodependencia 8,8%. El MESS (mangled extremity severity) promedio fue de 5,27 puntos y un tiempo critico de isquemia de extremidad > a 6 horas en el 38%. El mayor compromiso fue de miembros superiores, secundario a heridas por arma cortopunzante. La lesión predominante fue la transección arterial. Las principales complicaciones posquirúrgicas fueron la trombosis del vaso (21,5%) y la amputación (13,9%). Factores de riesgo asociados a amputación fueron la edad > 20 años, estancia hospitalaria > 7 días, MESS > 7 puntos, que presentaran como complicación quirúrgica la trombosis arterial y que requirieran reintervención quirúrgica. CONCLUSIONES: El trauma arterial periférico es una patología con gran repercusión socioeconómica y secuelas funcionales. Es necesaria la atención oportuna con tratamiento de las variables relacionadas con mal pronóstico, con el fin de disminuir las tasas de morbimortalidad.

INTRODUCTION: Vascular trauma is a low frequency event, with high morbidity and mortality that affects the young population; In general, it requires surgical management. It is associated with complications from surgical reintervention to amputation of the limb, influenced by trauma associated variables such as hospital care. AIM: Determine risk factors related to amputation, in patients with peripheral arterial trauma (TAP), treated at a Hospital of III level Huila-Colombia between 2014-2017. MATERIALS AND METHOD: Observational, retrospective analytical study with patients older than 13 years with TAP. RESULTS: We included 79 patients with an incidence of 1.56%. 89% men, average age 28.5 years. The main comorbidity was 8.8% drug dependence. The MESS (Mangled extremity severity) average was of 5.27 points and a critical time of limb ischemia > to 6 hours in 38%. The greater commitment was of superior members, secondary to injuries by sharp weapon. The predominant lesion was arterial transection. The main postoperative complications were vessel thrombosis (21.5%) and amputation in 13.9%. Risk factors associated with amputation were determined by age > 20 years, hospital stay > 7 days, MESS > 7 points, and that they presented arterial thrombosis as a surgical complication and finally required surgical reoperation. CONCLUSIONS: Peripheral arterial trauma is a pathology with great socioeconomic impact and functional sequelae. It is necessary the timely attention with treatment of the variables related to poor prognosis, in order to decrease the morbidity and mortality rates.

Experiencia en dos hospitales de tercer nivel de atención del suroccidente de Colombia en la aplicación del Registro Internacional de Trauma de la Sociedad Panamericana de Trauma / Experience with the implementation of the International Trauma Registry System at two tertiary care level hospitals in the Southwestern region of Colombia

Introducción. En el mundo se reconoce la importancia de los sistemas de registro de trauma. En Latinoamérica los sistemas disponibles de este tipo son poco confiables y no tienen continuidad. El del International Trauma System Development Program es el primero en implementarse en Colombia. Objetivo. Describir la experiencia de la implementación entre el 6 de enero y el 31 de julio de 2012 de un sistema de registro de trauma en dos hospitales de nivel III (equivalente al nivel I en complejidad de los hospitales en Estados Unidos) en Cali, Colombia. Método. El sistema de registro de trauma incluye información prehospitalaria y hospitalaria, y el estado al egreso del paciente, en tiempo real. Cada hospital tiene una estrategia para la captura electrónica de datos. Se presenta un análisis descriptivo y exploratorio de un ensayo piloto de siete meses. Resultados. Se registraron 9.080 pacientes en ambos hospitales. En el análisis global, el 67,1 % eran hombres; la edad promedio fue de 30 ± 20 años; el 68% eran mayores de 18 años. El 24,5 % de los pacientes fueron hospitalizados; de estos, 300 (13,5%) requirieron hospitalización en la unidad de cuidados intensivos. En cuanto a la gravedad del trauma, el 5,6 % de los pacientes tenía un puntaje de gravedad de las lesiones (Injury Severity Score, ISS) igual o mayor de 15. La tasa de mortalidad global fue del 3 %. Conclusión. Se logró la implementación del sistema de registro de trauma e identificar las causas de consulta, morbilidad y muerte por trauma. Esto contribuye al desarrollo de la investigación sobre pacientes con trauma, y a reorientar los servicios de urgencias y los del sistema regional de trauma y emergencias. Palabras clave: centros traumatológicos; índices de gravedad del trauma; puntaje de gravedad del traumatismo; registros electrónicos de salud.

Introduction: The importance of the Trauma Registry System is recognized worldwide. The available TRS in Latin America are unreliable and have no continuity. The International Trauma Registry of the Panamerican Trauma Society – International Trauma System Developing Program (ITSDP) is the first one to be implemented in Colombia. Objective: To describe the experience with the implementation of a TRS at two third level of care hospitals (equivalent to complexity level I in the United States) in Cali, Colombia, in the period January 6 to July 31, 2012. Method: TRS includes prehospital, hospital, and discharge status in real-time. Each hospital has its own electronic data capture strategy. A seven-month period pilot trial descriptive analysis is presented. Results: 9,080 patients were registered, 67,1% were male; mean age was 30,2 ± 20 years, 68,0% older than 18 years; 24.5% were hospitalized, of which 300 (13,5%) required ICU. Regarding severity of trauma, 5,6% of patients had ISS ≥ 15. Overall mortality rate was 3,0%. Conclusion: Implementation of the SRT was feasible and allowed the identification the cause of presentation, morbidity, and mortality rates. This improves research on trauma better direction of the emergency and trauma services.

Transfection analysis of expression of mRNA isoforms encoding the nuclear autoantigen La/SS-B.

Transcription of the gene encoding for the nuclear autoantigen La resulted in La mRNA isoforms. A promoter switching combined with an alternative splicing pathway replaced the exon 1 with the exon 1'. The exon 1' contained GC-rich regions and an oligo(U) tail of 23 uridine residues. Moreover, it encoded for three open reading frames upstream of the La protein reading frame. Despite this unusual structure, when exon 1' La mRNAs were expressed in transfected cells, both exon 1 and 1' La mRNAs were translated to La protein, whereas the upstream open reading frames of the exon 1' were not translated. In addition to full-length exon 1' La mRNAs 5'-shortened exon 1' La mRNAs were detected. The exon 1' 5'-starts varied in dependence on the analyzed tissues. Like the full-length exon 1' La mRNA a 5'-shortened exon 1' construct starting downstream of the oligo(U) tail but upstream of the open reading frames 2 and 3 was also well translated when transfected in mouse cells. Thus all La mRNA forms represent functional La mRNAs.

Identification and classification of differentially expressed genes in renal cell carcinoma by expression profiling on a global human 31,500-element cDNA array.

We investigated the changes in gene expression accompanying the development and progression of kidney cancer by use of 31,500-element complementary DNA arrays. We measured expression profiles for paired neoplastic and noncancerous renal epithelium samples from 37 individuals. Using an experimental design optimized for factoring out technological and biological noise, and an adapted statistical test, we found 1738 differentially expressed cDNAs with an expected number of six false positives. Functional annotation of these genes provided views of the changes in the activities of specific biological pathways in renal cancer. Cell adhesion, signal transduction, and nucleotide metabolism were among the biological processes with a large proportion of genes overexpressed in renal cell carcinoma. Down-regulated pathways in the kidney tumor cells included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Our expression profiling data uncovered gene expression changes shared with other epithelial tumors, as well as a unique signature for renal cell carcinoma. [Expression data for the differentially expressed cDNAs are available as a Web supplement at http://www.dkfz-heidelberg.de/abt0840/whuber/rcc.]