Cardiac tamponade and septic pericarditis caused by biliary stent migration.

In patients with biliary or pancreatic disease, endoscopic retrograde cholangiopancreatography (ERCP) is a common and important therapeutic and diagnostic procedure. Stent migration is a possible complication occurring in approximately 5-10% of cases. This case presents a 47-year-old male with chest pain and found to have biliary stent migration to the pericardial sac causing septic pericarditis and cardiac tamponade. Highlighting this devastating complication, this case demonstrates an opportunity for emergency physicians (EP) to diagnose and monitor patients for post-operative and post-procedural complications. In the emergency department, EPs are well positioned to use ultrasound as a diagnostic and monitoring tool for cardiac tamponade.

Uteroplacental Ischemia Is Associated with Increased PAPP-A2.

Residence at high altitude (> 2500 m) has been associated with an increased frequency of preeclampsia. Pappalysin-2 (PAPP-A2) is an insulin-like growth factor binding protein-5 (IGFBP-5) protease that is elevated in preeclampsia, and up-regulated by hypoxia in placental explants. The relationships between PAPP-A2, altitude, and indices of uteroplacental ischemia are unknown. We aimed to evaluate the association of altitude, preeclampsia, and uterine artery flow or vascular resistance with PAPP-A2 levels. PAPP-A2, uterine artery diameter, volumetric blood flow, and pulsatility indices were measured longitudinally in normotensive Andean women residing at low or high altitudes in Bolivia and in a separate Andean high-altitude cohort with or without preeclampsia. PAPP-A2 levels increased with advancing gestation, with the rise tending to be greater at high compared to low altitude, and higher in early-onset preeclamptic compared to normotensive women at high altitude. Uterine artery blood flow was markedly lower and pulsatility index higher in early-onset preeclamptic normotensive women compared to normotensive women. PAPP-A2 was unrelated to uterine artery pulsatility index in normotensive women but positively correlated in the early-onset preeclampsia cases. We concluded that PAPP-A2 is elevated at high altitude and especially in cases of early-onset preeclampsia with Doppler indices of uteroplacental ischemia.

Training Emergency Physicians in Ultrasound-guided Fascia Iliaca Compartment Blocks: Lessons in Change Management.

Study objectives Older adults who sustain hip fractures are susceptible to high rates of morbidity and mortality. The systemic administration of opioids is associated with side effects disproportionately affecting the elderly. The ultrasound-guided fascia iliaca compartment block procedure (FICB) is associated with a reduced patient need for oral and parenteral opioids and with improved functional outcomes. We designed a multi-disciplinary quality improvement initiative to train emergency physicians (EPs) to perform the ultrasound-guided FICB procedure for geriatric hip fracture patients. We examined the lessons derived from the EPs' resistance to implementing a practice-changing behavior. Methods This study was a prospective observational cohort study. We included all emergency department (ED) patients > 65 years with X-ray confirmation of isolated hip fractures. We also enrolled the treating EPs. Patients were enrolled from March 2016 to January 2017 in an urban, academic ED with 100,000 annual visits. The ED ultrasound faculty trained ED faculty and residents in the FICB procedure. Seventeen of 50 attending EPs completed the training: classroom lecture and online narrated video instruction. The hands-on sessions consisted of three stations: scan a human model volunteer to review the sonoanatomy, practice the needle technique using a Blue PhantomTM Regional Anesthesia Ultrasound Training Block Model (Simulaids, Inc., NY, US), and practice the needle technique using a static simulator. We created a multi-disciplinary geriatric hip fracture order set for the electronic medical record. The attending EPs, caring for eligible patients, were asked to complete a Research Electronic Data Capture (REDCap) survey, and we analyzed the data using descriptive statistics. Results We enrolled 77 geriatric hip fracture patients. Two of the 77 patients received FICB. Thirty-two EPs participated as providers for these patients while 97% of these providers completed the post-intervention survey. Providers used the geriatric hip fracture order set in 10 of 77 encounters. Most EPs did not perform the block because they were not trained or did not feel comfortable performing it. Conclusion Despite the efficacy supported by the literature and training sessions offered, the EPs in this study did not adopt the FICB procedure. Future efforts could include developing a FICB on-call team, increasing the proportion of trained EPs through initial supervised hands-on practice, and partnering financial or education incentives with getting trained.

An Easy-to-Make, Low-Cost Ultrasound Phantom for Simulation Training in Abscess Identification and Aspiration.

We have created a low-cost and easy to make phantom for abscess identification using point-of-care ultrasound. The phantom also allows needle tracking and abscess aspiration using ultrasound guidance.

Erythropoietin and Soluble Erythropoietin Receptor: A Role for Maternal Vascular Adaptation to High-Altitude Pregnancy.

Context: An imbalance of proangiogenic and antiangiogenic factors is thought to induce the widespread vascular dysfunction characteristic of preeclampsia (PreE). Erythropoietin (Epo), a pleiotropic cytokine, has important angiogenic and vasoactive properties; however, its contribution to maternal vascular dysfunction in PreE is unknown. Objectives: Because high altitude (HA) raises the incidence of PreE, we asked whether HA increased maternal Epo and soluble Epo receptor (sEpoR) levels and whether such effects differed between PreE and normotensive controls at HA. Design, Setting, and Participants: Longitudinal studies were conducted in pregnant Andean residents at HA (n = 28; 3600 m) or sea level (SL; n = 16; 300 m). Cross-sectional studies included 34 gestational age‒matched Andean PreE cases (n = 17) and controls (n = 17) in La Paz-El Alto, Bolivia (3600 to 4100 m). Results: HA augmented the pregnancy-associated rise in Epo relative to SL (P = 0.002), despite similar reductions in hemoglobin (Hb) across pregnancy at each altitude (7% to 9%, P < 0.001 for both). HA PreE cases had circulating Epo levels equivalent to those of controls but greater sEpoR (P < 0.05) and reduced Hb (P = 0.06, trend). Conclusion(s): Our findings suggest that an augmented pregnancy-associated rise in Epo may be important for successful vascular adaptation to pregnancy at HA. We further speculate that the elevated sEpoR observed in PreE vs controls at HA impedes the effect of Epo to maintain endothelial function and may, in turn, be of pathological relevance for PreE at HA.

Early Innovative Immersion: A Course for Pre-Medical Professions Students Using Point-of-Care Ultrasound.

In preparing for medical school admissions, premedical students seek opportunities to expand their medical knowledge. Knowing what students seek and what point-of-care ultrasound offers, we created a novel educational experience using point-of-care ultrasound. The innovation has 3 goals: (1) to use point-of-care ultrasound to highlight educational concepts such as the flipped classroom, simulation, hands-on interaction, and medical exposure; (2) to work collaboratively with peers; and (3) to expose premedical students to mentoring for the medical school application process. We believe that this course could be used to encourage immersive innovation with point-of-care ultrasound, progressive education concepts, and preparation for medical admissions.

Using Ultrasound to Enhance Medical Students' Femoral Vascular Physical Examination Skills.

OBJECTIVES: To determine whether the addition of ultrasound to traditional physical examination instruction improves junior medical students' abilities to locate the femoral pulse. METHODS: Initially, 150 second-year medical students were taught the femoral pulse examination using traditional bedside teaching on standardized patients and online didactic videos. Students were then randomized into 2 groups: group 1 received ultrasound training first and then completed the standardized examination; and group 2 performed the standardized examination first and then received ultrasound training. On the standardized patients, the femoral artery was marked with invisible ink before the sessions using ultrasound. Compared to these markers, students were then evaluated on the accuracy of femoral artery pulse palpation and the estimated location of the femoral vein. All students completed a self-assessment survey after the ultrasound sessions. RESULTS: Ultrasound training improved the students' ability to palpate the femoral pulse (P= .02). However, ultrasound did not facilitate correct estimation of the femoral vein's anatomic location (P = .09). Confidence levels in localizing the femoral artery and vein were equal between groups at baseline, and both increased after the ultrasound sessions. CONCLUSIONS: The addition of ultrasound teaching to traditional physical examination instruction enhanced medical student competency and confidence with the femoral vascular examination. However, understanding of anatomy may require emphasis on precourse didactic material, but further study is required.

Uterine artery blood flow, fetal hypoxia and fetal growth.

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.

Maternal PRKAA1 and EDNRA genotypes are associated with birth weight, and PRKAA1 with uterine artery diameter and metabolic homeostasis at high altitude.

Low birth weight and intrauterine growth restriction (IUGR) increase the risk of mortality and morbidity during the perinatal period as well as in adulthood. Environmental and genetic factors contribute to IUGR, but the influence of maternal genetic variation on birth weight is largely unknown. We implemented a gene-by-environment study wherein we utilized the growth restrictive effects of high altitude. Multigenerational high-altitude residents (Andeans) are protected from altitude-associated IUGR compared with recent migrants (Europeans). Using a combined cohort of low- and high-altitude European and Andean women, we tested 63 single nucleotide polymorphisms (SNPs) from 16 natural selection-nominated candidate gene regions for associations with infant birth weight. We identified significant SNP associations with birth weight near coding regions for two genes involved in oxygen sensing and vascular control, PRKAA1 and EDNRA, respectively. Next, we identified a significant association for the PRKAA1 SNP with an intermediate phenotype, uterine artery diameter, which has been shown to be related to Andean protection from altitude-associated reductions in fetal growth. To explore potential functional relationships for the effect of maternal SNP genotype on birth weight, we evaluated the relationship between maternal PRKAA1 SNP genotype and gene expression patterns in general and, in particular, of key pathways involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of IUGR. Our observations suggest that maternal genetic variation within genes that regulate oxygen sensing, metabolic homeostasis, and vascular control influence fetal growth and birth weight outcomes and hence Andean adaptation to high altitude.

Inhibition of peroxisome proliferator-activated receptor γ: a potential link between chronic maternal hypoxia and impaired fetal growth.

Chronic exposure to hypoxia raises the risk of pregnancy disorders characterized by maternal vascular dysfunction and diminished fetal growth. In an effort to identify novel pathways for these hypoxia-related effects, we assessed gene expression profiles of peripheral blood mononuclear cells (PBMCs) obtained from 43 female, high-altitude or sea-level residents in the nonpregnant state or during pregnancy (20 or 36 wk). Hypoxia-related fetal growth restriction becomes apparent between 25 and 29 wk of gestation and continues until delivery. Our sampling strategy was designed to capture changes occurring before (20 wk) and during (36 wk) the time frame of slowed fetal growth. PBMC gene expression profiles were generated using human gene expression microarrays and compared between altitudes. Biological pathways were identified using pathway analysis. Modest transcriptional differences were observed between altitudes in the nonpregnant state. Of the genes that were differentially expressed at high altitude vs. sea level during pregnancy (20 wk: 59 probes mapped to 41 genes; 36 wk: 985 probes mapped to 700 genes), several are of pathological relevance for fetal growth restriction. In particular, transcriptional changes were consistent with the negative regulation of peroxisome proliferator-activated receptor γ (PPARγ) at high altitude; such effects were accompanied by reduced birth weight (P <0.05) and head circumference (P <0.01) at high altitude vs. sea level. Our findings indicate that chronic exposure to hypoxia during pregnancy alters maternal gene expression patterns in general and, in particular, expression of key genes involved in metabolic homeostasis that have been proposed to play a role in the pathophysiology of fetal growth restriction.

Optic nerve sheath diameter and acute mountain sickness.

OBJECTIVE: Increased intracranial pressure (ICP) may contribute to acute mountain sickness (AMS). Measuring optic nerve sheath diameter (ONSD) by ultrasound (US) is a noninvasive technique to detect elevated ICP, and increased ONSD has been associated with AMS. We hypothesized that ONSD would increase with acute, rapid ascent to 4300 m and that increased ONSD would be associated with symptoms of AMS. We further hypothesized that treatment with oxygen at 4300 m would reduce symptoms and ONSD. METHODS: A cohort study was performed comparing US measurement of ONSD in healthy subjects at 1400 m and 18 hours after rapid ascent to 4300 m, both before and after oxygen treatment and between subjects with and without AMS (Lake Louise Score ≥3). RESULTS: Among 57 subjects, 29 (51%) experienced AMS after rapid ascent to 4300 m. In subjects without AMS, mean ONSD did not increase at 4300 m. In subjects with AMS, mean ONSD increased at 4300 m and was higher than in those without AMS. Treatment with oxygen lowered mean ONSD in subjects with AMS but not in those without AMS. Individual responses to altitude and oxygen varied greatly within groups, and the relationship between ONSD and AMS symptoms was weak. CONCLUSIONS: In this controlled study, mean ONSD increased in subjects with AMS at high altitude. However, individual variation was high, and most ONSD values were below the clinical threshold for raised ICP. Observed differences were small, of questionable clinical importance, and within the range of precision of the US machine. Overall, our data do not support a role for increased ICP in mild to moderate AMS.

Andean and Tibetan patterns of adaptation to high altitude.

OBJECTIVES: High-altitude hypoxia, or decreased oxygen levels caused by low barometric pressure, challenges the ability of humans to live and reproduce. Despite these challenges, human populations have lived on the Andean Altiplano and the Tibetan Plateau for millennia and exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. We and others have identified natural selection candidate genes and gene regions for these adaptations using dense genome scan data. One gene previously known to be important in cellular oxygen sensing, egl nine homolog 1 (EGLN1), shows evidence of positive selection in both Tibetans and Andeans. Interestingly, the pattern of variation for this gene differs between the two populations. Continued research among Tibetan populations has identified statistical associations between hemoglobin concentration and single nucleotide polymorphism (SNP) genotype at EGLN1 and a second gene, endothelial PAS domain protein 1 (EPAS1). METHODS: To measure for the effects of EGLN1 and EPAS1 altitude genotypes on hemoglobin concentration among Andean highlanders, we performed a multiple linear regression analysis of 10 candidate SNPs in or near these two genes. RESULTS: Our analysis did not identify significant associations between EPAS1 or EGLN1 SNP genotypes and hemoglobin concentration in Andeans. CONCLUSIONS: These results contribute to our understanding of the unique set of adaptations developed in different highland groups to the hypoxia of high altitude. Overall, the results provide key insights into the patterns of genetic adaptation to high altitude in Andean and Tibetan populations.

Role of cytokines in altitude-associated preeclampsia.

BACKGROUND: Preeclampsia (PE) is more common at high than low altitude and contributes to the altitude-related decline in birth weight. Since inflammatory markers are implicated in PE, we asked if such markers differed in PE vs. normotensive pregnant (NORM) women residing at high altitude (3600-4100 m), and were related to uterine artery blood flow (UA BF) or fetal growth. METHODS: Subjects were 33 Andean pregnant residents of Bolivia, comprising six with early-onset PE (≤ 34 wk), 12 with late-onset PE (> 34 wk), and 15 gestational-age matched NORM. Maternal pro- and anti-inflammatory cytokines were measured using a multiplex bead-based assay and UA BF by Doppler ultrasound. RESULTS: PE compared to NORM women had higher levels of the pro-inflammatory cytokines IL-6 and IL-8 as well as higher levels of the anti-inflammatory cytokine IL-1ra, but only IL-6 levels were higher when gestational age was controlled. Women with early- vs. late-onset PE had higher TNFα levels, and higher IL-6 was negatively correlated with birth weight in all women at ≤ 34 wk. We suggest that pro-inflammatory factors influence both the timing and severity of PE at high altitude.

Potential role for elevated maternal enzymatic antioxidant status in Andean protection against altitude-associated SGA.

Oxidative stress has been implicated in the uteroplacental ischemia characteristic of preeclampsia and small-for-gestational-age (SGA) birth, both of which are more common at high (>2500 m) vs low altitude. Since Andeans are protected relative to Europeans from the altitude-associated rise in SGA, we asked whether alterations in maternal antioxidant status or oxidative stress contributed to their protection. Enzymatic antioxidant (erythrocyte catalase and superoxide dismutase [SOD]) activity and a plasma marker of lipid peroxidation (8-iso-PGF2α) were measured during pregnancy and in the non-pregnant state in Andean or European residents of low (400 m) or high altitude (3600-4100 m). Pregnancy and altitude increased catalase and/or SOD activity to a greater extent in Andeans than Europeans. 8-iso-PGF2α levels were independent of altitude and pregnancy. SOD was lower in mothers of SGA infants at weeks 20 and 36. Our findings are consistent with the possibility that elevated enzymatic antioxidant activity contributes to Andean protection against altitude-associated SGA.

High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude.

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (Q(UA)). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600-4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ~0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. Q(UA) was lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left Q(UA) was consistently greater than right in NORM, but the pattern reversed in PE. Although Q(CI) and Q(EI) were higher in PE and GH than NORM, the fraction of Q(CI) distributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced Q(UA) (R(2) = 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited Q(UA) and restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of Q(UA) and pelvic blood flow in early- vs. late-onset PE in high-altitude residents.

Do cytokines contribute to the Andean-associated protection from reduced fetal growth at high altitude?

Pro- versus anti-inflammatory cytokine balance is important for successful pregnancy. Chronic hypoxia alters cytokine levels and increases the frequency of fetal growth restriction (FGR). Multigenerational Andean (AND) versus shorter duration European (EUR) high-altitude (HA) residents are protected from altitude-associated FGR. To address whether ancestry group differences in cytokine levels were involved, we conducted serial studies in 56 low-altitude ([LA]; 400 m; n = 29 AND and n = 27 EUR) and 42 HA residents (3600-4100 m; n = 19 ANDs and n = 23 EURs). Pregnancy raised pro- (interleukin 1ß [IL-1ß]) and anti- (IL-10) inflammatory cytokines and HA lowered IL-6 and tumor necrosis factor-α (TNF-α) near term. There were no ancestry group differences in cytokine levels at any time, but HA reduced IL-1ß in ANDs only near term. Higher IL-1ß levels correlated with uterine artery (UA) blood flow at 20 weeks in ANDs at HA, suggesting that IL-1ß may play a role in AND protection from altitude-associated reductions in fetal growth.

Do anti-angiogenic or angiogenic factors contribute to the protection of birth weight at high altitude afforded by Andean ancestry?

OBJECTIVE: This prospective study was designed to determine whether variation in angiogenic (placental growth factor [PlGF]) and/or anti-angiogenic (soluble fms-like tyrosine kinase [sFlt-1]) factors contribute to the protective effect of highland ancestry (Andean) from altitude-associated reductions in fetal growth. STUDY DESIGN: Plasma sFlt-1 and PlGF levels, uterine artery (UA) blood flow, and fetal biometry were determined in low-altitude (400 m; Andean n = 27, European n = 28) and high-altitude (3600 m; Andean n = 51, European n = 44) residents during pregnancy (20 and 36 weeks) and 4 months postpartum. RESULTS: High-altitude decreased sFlt-1 levels in both groups, Andeans had lower sFlt-1, comparable PlGF, lower sFlt-1/PlGF ratios, and higher UA blood flow throughout pregnancy relative to Europeans. Altitude decreased birth weight in Europeans but not Andeans. In high-altitude Europeans sFlt-1/PlGF and sFlt-1 levels were negatively associated with UA diameter and birth weight, respectively. CONCLUSIONS: Lower sFlt-1 and sFlt-1/PLGF ratio may contribute to or result from variations in maternal vascular adaptation to pregnancy between Andean and Europeans at high altitude. Subsequently, these effects could potentially influence ancestry-associated differences in birth weight.

Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial.

BACKGROUND: Acute mountain sickness (AMS) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis; however, there is conflicting evidence regarding the efficacy of Ginkgo biloba use. We performed a randomized, placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis. METHODS: We randomized unacclimatized adults to receive acetazolamide, Ginkgo biloba, or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours. We graded AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System (LLS) and compared the incidence of AMS (defined as LLS score > or =3 and headache). RESULTS: Fifty-seven subjects completed the trial (20 received acetazolamide; 17, Ginkgo biloba, and 20, placebo). The LLS scores were significantly different between groups; the median score of the acetazolamide group was significantly lower than that of the placebo group (P=.01; effect size, 2; and 95% confidence interval [CI], 0 to 3), unlike that of the Ginkgo biloba group (P=.89; effect size, 0; and 95% CI, -2 to 2). Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group (effect size, 30%; 95% CI, 61% to -15%), and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group (effect size, -5%; 95% CI, -37% to 28%). CONCLUSIONS: In this study, prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence. We found no evidence of similar efficacy for Ginkgo biloba.