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Ipsilateral axillary adenopathy post-COVID mRNA vaccine has been widely reported and guidelines for management have been established. Isolated changes of axillary tail trabecular thickening without associated adenopathy in the breast present a diagnostic dilemma and no official guidelines have thus far been reported. This finding has been reported after COVID mRNA vaccine and has never been reported with any other vaccine. We report on a patient with such changes on screening mammography 1.5 months after the fifth dose of a COVID-mRNA vaccine and 1 week after RSV vaccine. This raises the possibility that such changes can be seen with vaccines other than the COVID mRNA series of vaccines. The main differential diagnosis includes mastitis and inflammatory breast cancer. The transient nature of this finding with spontaneous resolution at diagnostic mammography and the vaccination history helps to establish the diagnosis and exclude breast cancer.

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, utilizing either a staged repair (SR) or primary repair (PR) approach. They are exposed to several sources of low-dose ionizing radiation, which may contribute to increased cancer risk. Objectives: The purpose of this study was to compare cumulative radiation exposure and associated lifetime attributable risk (LAR) of cancer between treatment strategies in sTOF. Methods: Neonates with sTOF who underwent SR or PR from 2012 to 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Radiation exposure from all radiologic studies prior to 18 months of age was converted to organ-equivalent doses and projected LAR of cancer incidence using the National Cancer Institute dosimetry tools. Results: There were 242 neonates from 8 centers, including patients with 146 SR and 96 PR. Cumulative total effective dose was significantly higher for SR (median 8.3 mSv, IQR: 3.0-17.4 mSv) than PR (2.1 mSv, IQR: 0.8-8.5 mSv; P 1 mGy in females, the LAR was highest for breast in SR (mean 1.9/1,000 patients). The highest proportion of cancers attributable to radiation exposure was projected for thyroid cancer in females undergoing SR (7.3%). Conclusions: Cumulative radiation exposure and LARs were higher among those undergoing SR compared to PR. This will be an important factor to consider in determining the preferred neonatal treatment strategy and should substantiate efforts to reduce radiation exposure in this vulnerable population.

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit.

The COVID-19 pandemic has seen a massive shift toward virtual living, with video-conferencing now a primary means of communication for both work and social events. Individuals are finding themselves staring at their own video reflection, often for hours a day, scrutinizing a distorted image on screen and developing a negative self-perception. This survey study of over 100 board-certified dermatologists across the country elucidates a new problem of Zoom dysmorphia, where patients seek cosmetic procedures to improve their distorted appearance on video-conferencing calls.

Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and a heart chamber resulting in left-to-right shunt. A large CAF was an unexpected cause of heart failure in a 58-year-old woman who underwent transcatheter closure of the CAF with improvement in symptoms but complicated by myocardial infarction. (Level of Difficulty: Beginner.)

To examine perceptions about the diagnostic process and post-diagnosis care of type 2 diabetes (T2D) from adolescent patients, parents, and diabetes care physicians, semi-structured interviews were conducted with 8 individuals from each group. Interview transcripts were coded using content analysis. Emerged categories were compared among 3 groups. Half of adolescent patients and parents were surprised by the T2D diagnosis, despite most reporting that patients experienced common symptoms of T2D prior to diagnosis. Adolescents and parents recognized diet, exercise, and weight gain as risk factors after diagnosis, whereas physicians noted weight gain as a common risk factor pre-diagnosis. All 3 groups noted the importance of maintaining a healthy lifestyle and adherence to T2D management, though physicians noted the challenges from socioeconomic structural inequalities. Adolescent and parents were surprised by the T2D diagnosis, suggesting the need for increasing awareness of risk factors and symptomatology of T2D among at-risk adolescents and parents.

Introduction In the unprecedented era of COVID-19, ongoing research and evolution of evidence has led to ever-changing guidelines for clinical monitoring and therapeutic options. Formulating treatment protocols requires the understanding and application of the evolving research. Objective The primary objective of this study is to present a systematic evidence-based approach to synthesize the necessary data in order to optimize the management of COVID-19. Methods At Mayo Clinic Florida, we developed a multidisciplinary centralized COVID Treatment Review Panel (TRP) of expert pulmonologists, intensivists, infectious disease specialists, anesthesiologists, hematologists, rheumatologists, and hospitalists that in real-time reviews the latest evidence in peer-reviewed journals, the available clinical trials, and help guide the rapid application of therapeutics or interventions to the patient and the bedside provider. Results/Conclusions The multi-disciplinary team approach of synthesizing clinical data and coordinating care is effective in responding to rapidly evolving and changing evidence. Systematic data collection and evidence-based treatment algorithms enable physicians to rapidly translate the current literature to clinical practice, and improve care and outcomes of patients.

Objective: To reduce door-to-angiographic reperfusion (DTR) time to 120 minutes for patients presenting with acute ischemic stroke attributed to anterior circulation large-vessel occlusion amenable to endovascular mechanical thrombectomy. Patients and Methods: Patients treated with mechanical thrombectomy before (April 10, 2015, through April 11, 2016) and after (April 12, 2016, through May 10, 2017) implementation of a multitiered notification system were studied. Lean process mapping was used to assess inefficiencies with multidisciplinary triage. A 3-tiered paging platform, which rapidly alerts essential personnel of the acute ischemic stroke team at advancing decision points, was introduced. Results: Sixty-two patients were analyzed before and after implementation (34 vs 28, respectively). Following intervention, DTR time was reduced by 43 minutes (mean DTR, 170 minutes vs 127 minutes; P=.02). At 90-day follow up, 5 of the 28 patients in the postintervention cohort (19%) had excellent neurologic outcomes, defined as a modified Rankin Scale score of 0, compared to 0 of 34 (0%) in the preintervention cohort (P=.89). Reductions were also seen in the length of stay on the neurocritical care service (mean, 6 vs 3 days; P=.006), and total hospital charges for combined groups (mean, $100,083 vs $161,458; P

Background. Aerococcus urinae is a rare causative pathogen of infective endocarditis that results in a high risk of embolic events. The mortality rate for A urinae endocarditis is high. Old age and underlying urologic conditions are the best-known risk factors for infection. Case Description. We report the clinical course of the disease in a 49-year-old man who presented symptoms of a urinary tract infection. A few days later, transthoracic echocardiography showed a conspicuous mitral valve with myxomatous alterations. Following the detection of a cerebral embolism with associated stroke symptoms, as well as at the beginning of cardiac failure, the emergency indication for the surgical treatment of mitral valve endocarditis was given. On the second day following the operation, circulatory collapse rapidly developed. Following an unsuccessful attempt at cardiopulmonary resuscitation, the patient died. Review of the Literature. From 1991 to 2017, 29 cases of A urinae –induced endocarditis have been described in PubMed and Medline. One or 2 new cases are published annually. We review all reported cases of A urinae endocarditis, with an emphasis on the predisposing factors, course, and outcomes of the disease. Conclusion. A urinae endocarditis is a rare disease primarily affecting elderly men with urinary tract pathologies and comorbidities. The course of the disease is severe, and the outcome is often fatal. A 16S rDNA polymerase chain reaction investigation of bacterial genome provides proof of the presence of A urinae . Because of the high risk of embolism, rapid treatment should focus on the diseased heart valve. Based on existing data and the experience gained from handling cases, treatment with β-lactam and aminoglycosides is recommended. It is also recommended that operative therapy take place as soon as possible.

Purpose: PGN650 is a F(ab′) 2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124 I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124 I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124 I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies.

ABSTRACT: Objective: Congenital adrenal hyperplasia (CAH) can result in hormonal changes that influence gender identification and possibly the formation of adrenal myelolipomas in rare cases.Methods: A patient case is presented with associated literature review.Results: A 46,XX patient with 21-hydroxylase deficiency who had ambiguous genitalia at birth that were surgically revised to a female phenotype is reported. The patient was intermittently compliant with glucocorticoid therapy. Years later, because of his male gender identification, he had a legal name change and gender reversal surgery to male. At age 46 he was found to have bilateral giant adrenal myelolipomas that were surgically removed.Conclusion: Treatment objectives in the care of patients with CAH include adequate glucocorticoid replacement to reduce increased corticotropin-releasing hormone and corticotropin secretion that result in hyperandrogenemia so that growth, sexual maturation, and reproductive function, as well as psychosocial development, are normal. There is also an increasing appreciation for addressing the complexities of gender identity and the timing of genital revision surgery in these patients. There is increasing anecdotal evidence that a subset of patients who are not optimally treated may develop adrenal myelolipomas.Abbreviations:17-OHP = 17-hydroxyprogesteroneACTH = adrenocorticotropic hormoneAI = adrenal incidentalomaCAH = congenital adrenal hyperplasia

IntroductionThe validity of self-reported data for mammography differ by race. We assessed the effect of racial differences in the validity of age-adjusted, self-reported mammography use estimates from the Behavioral Risk Factor Surveillance System (BRFSS) from 1995 through 2006 to determine whether misclassification (inaccurate survey question response) may have obscured actual racial disparities.MethodsWe adjusted BRFSS mammography use data for age by using 2000 census estimates and for misclassification by using the following formula: (estimated prevalence − 1 + specificity) / (sensitivity + specificity − 1). We used values reported in the literature for the formula (sensitivity = 0.97 for both black and white women, specificity = 0.49 and 0.62, respectively, for black and white women).ResultsAfter adjustment for misclassification, the percentage of women aged 40 years or older in 1995 who reported receiving a mammogram during the previous 2 years was 54% among white women and 41% among black women, compared with 70% among both white and black women after adjustment for age only. In 2006, the percentage after adjustment for misclassification was 65% among white women and 59% among black women compared with 77% among white women and 78% among black women after adjustment for age only.ConclusionSelf-reported data overestimate mammography use — more so for black women than for white women. After adjustment for respondent misclassification, neither white women nor black women had attained the Healthy People 2010 objective (≥70%) by 2006, and a disparity between white and black women emerged.

Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days.Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI.Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 microg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days.Measurements and Main Results: APC increased plasma protein C levels (P = 0.002) and decreased pulmonary dead space fraction (P = 0.02). However, there was no statistically significant difference between patients receiving placebo (n = 38) or APC (n = 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P = 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P = 1.0). There were no differences in the number of bleeding events between the two groups.Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity. [ABSTRACT FROM AUTHOR]

Challenges in using cytokine data are limiting Coronavirus Disease 2019 (COVID-19) patient management and comparison among different disease contexts. We suggest mitigation strategies to improve the accuracy of cytokine data, as we learn from experience gained during the COVID-19 pandemic., Competing Interests: The authors have declared that no competing interests exist.

Background and Rationale : ICU clinicians regularly care for patients who lack capacity, an applicable advance directive, and an available surrogate decision-maker. Although there is no consensus on terminology, we refer to these patients as "unrepresented." There is considerable controversy about how to make treatment decisions for these patients, and there is significant variability in both law and clinical practice. Purpose and Objectives : This multisociety statement provides clinicians and hospital administrators with recommendations for decision-making on behalf of unrepresented patients in the critical care setting. Methods : An interprofessional, multidisciplinary expert committee developed this policy statement by using an iterative consensus process with a diverse working group representing critical care medicine, palliative care, pediatric medicine, nursing, social work, gerontology, geriatrics, patient advocacy, bioethics, philosophy, elder law, and health law. Main Results : The committee designed its policy recommendations to promote five ethical goals: 1 ) to protect highly vulnerable patients, 2 ) to demonstrate respect for persons, 3 ) to provide appropriate medical care, 4 ) to safeguard against unacceptable discrimination, and 5 ) to avoid undue influence of competing obligations and conflicting interests. These recommendations also are intended to strike an appropriate balance between excessive and insufficient procedural safeguards. The committee makes the following recommendations: 1 ) institutions should offer advance care planning to prevent patients at high risk for becoming unrepresented from meeting this definition; 2 ) institutions should implement strategies to determine whether seemingly unrepresented patients are actually unrepresented, including careful capacity assessments and diligent searches for potential surrogates; 3 ) institutions should manage decision-making for unrepresented patients using input from a diverse interprofessional, multidisciplinary committee rather than ad hoc by treating clinicians; 4 ) institutions should use all available information on the patient's preferences and values to guide treatment decisions; 5 ) institutions should manage decision-making for unrepresented patients using a fair process that comports with procedural due process; 6 ) institutions should employ this fair process even when state law authorizes procedures with less oversight. Conclusions : This multisociety statement provides guidance for clinicians and hospital administrators on medical decision-making for unrepresented patients in the critical care setting.

Background: The Accreditation Council for Graduate Medical Education requires each residency program to have a Program Evaluation Committee (PEC) but does not specify how the PEC should be designed. We sought to develop a PEC that promotes resident leadership and provides actionable feedback., Methods: Participants were residents and faculty in the Traditional Internal Medicine residency program at Yale School of Medicine (YSM). One resident and one faculty member facilitated a 1-h structured group discussion to obtain resident feedback on each rotation. PEC co-facilitators summarized the feedback in written form, then met with faculty Firm Chiefs overseeing each rotation and with residency program leadership to discuss feedback and generate action plans. This PEC process was implemented in all inpatient and outpatient rotations over a 4-year period. Upon conclusion of the second and fourth years of the PEC initiative, surveys were sent to faculty Firm Chiefs to assess their perceptions regarding the utility of the PEC format in comparison to other, more traditional forms of programmatic feedback. PEC residents and faculty were also surveyed about their experiences as PEC participants., Results: The PEC process identified many common themes across inpatient and ambulatory rotations. Positives included a high caliber of teaching by faculty, highly diverse and educational patient care experiences, and a strong emphasis on interdisciplinary care. Areas for improvement included educational curricula on various rotations, interactions between medical and non-medical services, technological issues, and workflow problems. In survey assessments, PEC members viewed the PEC process as a rewarding mentorship experience that provided residents with an opportunity to engage in quality improvement and improve facilitation skills. Firm chiefs were more likely to review and make rotation changes in response to PEC feedback than to traditional written resident evaluations but preferred to receive both forms of feedback rather than either alone CONCLUSIONS: The PEC process at YSM has transformed our program's approach to feedback delivery by engaging residents in the feedback process and providing them with mentored quality improvement and leadership experiences while generating actionable feedback for program-wide change. This has led to PEC groups evaluating additional aspects of residency education.

Background: Several specialty societies participate in the Choosing Wisely (CW) campaign in an attempt to reduce waste in health care spending. We surveyed internal medicine (IM) residents with an objective of classifying knowledge of and confidence in using the American Society of Hematology (ASH) CW principles in hemostasis, thrombosis, and non-malignant hematology., Methods: Multi-institutional study of IM residents at 5 academic training programs in the United States. A 10-question, case-based multiple choice test, with each question accompanied by a 5-point Likert-scale confidence assessment, was distributed electronically. Responses were summarized with frequencies and percentages or medians and ranges, as appropriate. Two sample t-tests or Wilcoxon rank-sum tests were used to compare confidence and knowledge scores., Results: Of 892 IM residents, 174 (19.5%) responded to all questions. Overall, residents answered a median of 7 of 10 questions correctly (range 2-10) and median resident confidence in their responses was 3.1 (on a 5-point scale). Correct responses were significantly associated with higher confidence for all but one question. Having a hematology rotation experience was significantly associated with more correct responses and with higher confidence (p = 0.001 and p<0.001, respectively)., Conclusions: IM residents at several academic hospitals have variable knowledge of ASH-CW guidelines in thrombosis and hemostasis/non-malignant hematology. Residents who have done hematology rotations, particularly a hematology consult rotation, were more likely to answer questions correctly and to be more confident that their answers were correct. Adequate clinical exposure and training in cost-effective care is essential to train clinicians who are cost-conscious in any specialty.

Rationale: Intensive care unit (ICU) clinicians sometimes have a conscientious objection (CO) to providing or disclosing information about a legal, professionally accepted, and otherwise available medical service. There is little guidance about how to manage COs in ICUs., Objectives: To provide clinicians, hospital administrators, and policymakers with recommendations for managing COs in the critical care setting., Methods: This policy statement was developed by a multidisciplinary expert committee using an iterative process with a diverse working group representing adult medicine, pediatrics, nursing, patient advocacy, bioethics, philosophy, and law., Main Results: The policy recommendations are based on the dual goals of protecting patients' access to medical services and protecting the moral integrity of clinicians. Conceptually, accommodating COs should be considered a "shield" to protect individual clinicians' moral integrity rather than as a "sword" to impose clinicians' judgments on patients. The committee recommends that: (1) COs in ICUs be managed through institutional mechanisms, (2) institutions accommodate COs, provided doing so will not impede a patient's or surrogate's timely access to medical services or information or create excessive hardships for other clinicians or the institution, (3) a clinician's CO to providing potentially inappropriate or futile medical services should not be considered sufficient justification to forgo the treatment against the objections of the patient or surrogate, and (4) institutions promote open moral dialogue and foster a culture that respects diverse values in the critical care setting., Conclusions: This American Thoracic Society statement provides guidance for clinicians, hospital administrators, and policymakers to address clinicians' COs in the critical care setting.

There are two different ways to model reactive transport: ad hoc and innovative reaction-based approaches. The former, such as the Kd simplification of adsorption, has been widely employed by practitioners, while the latter has been mainly used in scientific communities for elucidating mechanisms of biogeochemical transport processes. It is believed that innovative mechanistic-based models could serve as protocols for environmental remediation as well. This paper reviews the development of a mechanistically coupled fluid flow, thermal transport, hydrologic transport, and reactive biogeochemical model and example-applications to environmental remediation problems. Theoretical bases are sufficiently described. Four example problems previously carried out are used to demonstrate how numerical experimentation can be used to evaluate the feasibility of different remediation approaches. The first one involved the application of a 56-species uranium tailing problem to the Melton Branch Subwatershed at Oak Ridge National Laboratory (ORNL) using the parallel version of the model. Simulations were made to demonstrate the potential mobilization of uranium and other chelating agents in the proposed waste disposal site. The second problem simulated laboratory-scale system to investigate the role of natural attenuation in potential off-site migration of uranium from uranium mill tailings after restoration. It showed inadequacy of using a single Kd even for a homogeneous medium. The third example simulated laboratory experiments involving extremely high concentrations of uranium, technetium, aluminum, nitrate, and toxic metals (e.g., Ni, Cr, Co). The fourth example modeled microbially-mediated immobilization of uranium in an unconfined aquifer using acetate amendment in a field-scale experiment. The purposes of these modeling studies were to simulate various mechanisms of mobilization and immobilization of radioactive wastes and to illustrate how to apply reactive transport models for environmental remediation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of acute lung injury (ALI) have previously been associated with poorer clinical outcomes and increased disease severity among patients with ALI. Whether these biomarkers have predictive value in a less severely ill population that excludes septic patients with high APACHE II scores is currently unknown. We tested the association of plasma and BAL biomarkers with physiological markers of ALI severity or clinically relevant outcomes in a secondary analysis of a clinical trial of activated protein C for the treatment of ALI. Plasma plasminogen activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly associated with increased oxygenation index (P = 0.02 and 0.01, respectively), whereas there was a trend toward an association between IL-6 and oxygenation index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01, 0.01, and 0.05, respectively); no markers were associated with mortality, but we hypothesized that this was due to the small size of our cohort and the low death rate. To confirm these associations in a larger sample, we identified a restricted cohort of patients from the ARDS Network ALVEOLI study with similar baseline characteristics. We retested the associations of the significant biomarkers with markers of severity and clinical outcomes and studied IL-8 as an additional biomarker given its important predictive value in prior studies. In this restricted cohort, IL-6 was significantly associated with oxygenation index (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased 28-day mortality. Future studies should be focused on examining larger numbers of patients with less severe ALI to further test the relative predictive value of plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs and mortality, and for their prospective utility in risk stratification for future clinical trials.

Background: Safe and timely oral alimentation is crucial for optimum patient care., Objective: To determine the short-term success of recommending specific oral diets, including drinking thin liquids, to acute care hospitalized patients at risk for dysphagia based on passing a 3-ounce water swallow challenge protocol., Design: Prospective single group consecutively referred case series., Setting: Large, urban, tertiary care, teaching hospital., Participants: 1000 hospitalized patients., Intervention: 3-ounce (90 cc) water swallow challenge protocol., Measurements: Specific diet recommendations and volume (in cc) of liquid ingested at the next day's meal 12-24 h after passing a 3-ounce challenge protocol were accessed electronically from oral intake information entered on each participant's daily care logs. Eating and drinking success, clinically evident aspiration events and compliance with ordering the recommended diet were recorded. Care providers were blinded to the study's purpose., Results: Of 1000 patients, 907 met the inclusion criteria of stable medical, surgical or neurological conditions 12-24 h after passing a 3-ounce water swallow challenge protocol. All 907 were both eating and drinking thin liquids successfully and without overt signs of dysphagia. Median volume of liquid ingested was 340 cc [interquartile range (IQR), 240-460]. Specific diet recommendations were followed with 100% accuracy., Conclusion: A 3-ounce water swallow challenge protocol successfully identified patients who can be safely advanced to an oral diet without subsequent identification of overt signs of aspiration within 12-24 h of testing. Importantly, when a clinical 3-ounce challenge protocol administered by a trained provider is passed, specific diet recommendations, including drinking thin liquids, can be made safely and without the need for additional instrumental dysphagia testing.

The vascular growth factor angiopoietin 2 (Ang-2) is known to promote inflammation and endothelial dysfunction, but its prognostic capacity and relationship to outcomes in human sepsis are unknown. This is a prospective observational cohort study of 66 patients newly admitted to a tertiary care medical intensive care unit (ICU), which included ICU patients with no sepsis (n = 20) as well as those with sepsis (n = 10), severe sepsis (n = 12), and septic shock (n = 24). Clinical data were collected until hospital discharge, and Ang-2 and IL-6 levels were determined on specimens obtained after ICU admission. Serum Ang-2 correlated with IL-6 and severity-of-illness scores. In the septic cohort, circulating Ang-2 levels were significantly higher (P = 0.01) in those who died (24.9 ng/mL; interquartile range, 21.5-38.0 ng/mL) compared with those who survived (13.5 ng/mL; interquartile range, 8.1-21.6 ng/mL). Elevated circulating serum Ang-2 levels are associated with increased hospital mortality in patients with sepsis.

Objective: In a recent randomized controlled trial, lowering blood glucose levels to 80-110 mg/dl improved clinical outcomes in critically ill patients. In that study, the insulin infusion protocol (IIP) used to normalize blood glucose levels provided valuable guidelines for adjusting insulin therapy. In our hands, however, ongoing expert supervision was required to effectively manage the insulin infusions. This work describes our early experience with a safe, effective, nurse-implemented IIP that provides detailed insulin dosing instructions and requires minimal physician input., Research Design and Methods: We collected data from 52 medical intensive care unit (MICU) patients who were placed on the IIP. Blood glucose levels were the primary outcome measurement. Relevant clinical variables and insulin requirements were also recorded. MICU nurses were surveyed regarding their experience with the IIP., Results: To date, our IIP has been employed 69 times in 52 patients admitted to an MICU. Using the IIP, the median time to reach target blood glucose levels (100-139 mg/dl) was 9 h. Once blood glucose levels fell below 140 mg/dl, 52% of 5,808 subsequent hourly blood glucose values fell within our narrow target range; 66% within a "clinically desirable" range of 80-139 mg/dl; and 93% within a "clinically acceptable" range of 80-199 mg/dl. Only 20 (0.3%) blood glucose values were <60 mg/dl, none of which resulted in clinically significant adverse events. In general, the IIP was readily accepted by our MICU nursing staff, most of whom rated the protocol as both clinically effective and easy to use., Conclusions: Our nurse-implemented IIP is safe and effective in improving glycemic control in critically ill patients.

The couplings among chemical reaction rates, advective and diffusive transport in fractured media or soils, and changes in hydraulic properties due to precipitation and dissolution within fractures and in rock matrix are important for both nuclear waste disposal and remediation of contaminated sites. This paper describes the development and application of LEHGC2.0, a mechanistically based numerical model for simulation of coupled fluid flow and reactive chemical transport, including both fast and slow reactions in variably saturated media. Theoretical bases and numerical implementations are summarized, and two example problems are demonstrated. The first example deals with the effect of precipitation/dissolution on fluid flow and matrix diffusion in a two-dimensional fractured media. Because of the precipitation and decreased diffusion of solute from the fracture into the matrix, retardation in the fractured medium is not as large as the case wherein interactions between chemical reactions and transport are not considered. The second example focuses on a complicated but realistic advective-dispersive-reactive transport problem. This example exemplifies the need for innovative numerical algorithms to solve problems involving stiff geochemical reactions.

Interleukin-5 (IL-5) plays a central role in the growth and differentiation of eosinophils and contributes to several disease states including asthma. Accumulating evidence suggests a role for cAMP as an immunomodulator; agents that increase intracellular cAMP levels have been shown to inhibit production of cytokines predominantly produced by T helper (Th) 1 cells such as IL-2 and interferon gamma (IFN-gamma). In contrast, the production of IL-5, predominantly produced by Th2 cells, is actually enhanced by these agents. In this report, we have performed transient transfection experiments with IL-5 promoter-reporter gene constructs, DNase I footprinting assays, and electrophoretic mobility shift assays to investigate the key regulatory regions necessary for activation of the IL-5 promoter by dibutyryl cAMP and phorbol esters in the mouse thymoma line EL-4. Taken together, our data demonstrate the critical importance of two sequences within the IL-5 5'-flanking region for activation by these agents in EL-4 cells: one, a highly conserved 15-base pair element present in genes expressed by Th2 cells, called the conserved lymphokine element 0 (CLE0; located between -53 and -39 in the IL-5 promoter), and the other, two overlapping binding sites for the transcription factor GATA-3 (but not GATA-4) between -70 and -59. Taken together, our data suggest that activation via the unique sequence combination GATA/CLE0 results in selective expression of the IL-5 gene in response to elevated levels of intracellular cAMP.

Platy intergrowths of crystalline todorokite are associated with biogenic debris in the cores of manganese nodules from a site in the Pacific Ocean. Analyses by electron diffraction and transmission electron microscopy demonstrate that this material is composed of tunnels of chains of linked MnO(6) octahedra. The chemical composition, morphology, and stability of the todorokite differ from those of nickel-and copper-rich manganese oxides in nodules that have been identified as todorokite or buserite in earlier investigations.