The clinical and economic costs of delirium after surgical resection for esophageal malignancy.

OBJECTIVE: The aim of this study was to identify preoperative risk factors and postoperative consequences that are associated with the occurrence of delirium after esophagectomy for malignancy. BACKGROUND: Delirium is an underdiagnosed, serious complication after major surgery, particularly in the elderly population. METHODS: All patients undergoing esophagectomy for cancer (1991-2011) were included. Patients with and without delirium were compared with respect to medical comorbidities, use of neoadjuvant therapy, operative outcomes, postoperative complications, overall cost, and survival. RESULTS: Of the 500 patients included in this analysis, 46 (9.2%) patients developed postoperative delirium. Patients with delirium had higher ASA and Charlson comorbidity index scores. Delirium was associated with a longer hospital (14 ± 7.5 vs 10.9 ± 5.7; P < 0.05) and intensive care unit stay (3.6 ± 3.8 vs 2.7 ± 16.9; P < 0.05) and an increased incidence of pulmonary complications and increased hospital costs. Delirium was preceded by another complication in 32.6% of cases but by a septic complication in only 19.6% of cases. Age was the only preoperative predictor of postoperative delirium in multivariate modeling (P < 0.05). No differences were noted in the use of neoadjuvant chemoradiotherapy or survival. CONCLUSIONS: This study demonstrates that postoperative delirium is associated with a more complicated and costly recovery after esophagectomy and that age is independently predictive of its development. Delirium has often been thought to be the sequela of other complications; however, this study demonstrates that it presents in isolation or precedes other complications in 67.4% of cases. Focused screening will likely allow targeted preventative strategies to be used in the perioperative period to reduce complications and costs associated with delirium.

Urban green space and albedo impacts on surface temperature across seven United States cities.

Extreme heat represents a growing threat to public health, especially across the densely populated, developed landscape of cities. Climate adaptation strategies that aim to manage urban microclimates through purposeful design can reduce the heat exposure of urban populations, however, it is unclear how the temperature impacts of urban green space and albedo vary across cities and background climate. This study quantifies the sensitivity of surface temperature to landcover characteristics tied to two widely used climate adaptation strategies, urban greening and albedo manipulation (e.g. white roofs), by combining long-term remote sensing observations of land surface temperature, albedo, and moisture with high-resolution landcover datasets in a spatial regression analysis at the census block scale across seven United States cities. We find tree cover to have an average cooling impact of -0.089 K per % cover, which is approximately four times stronger than the average grass cover cooling impact of -0.021 K per % cover. Variability in the magnitude of grass cover cooling impacts was primarily a function of vegetation moisture content, with the Land Surface Water Index (LSWI) explaining 89 % of the variability in grass cover cooling impacts across cities. Variability in tree cover cooling impacts was primarily a function of sunlight and vegetation moisture content, with solar irradiance and LSWI explaining 97 % of the cooling variability across cities. Albedo cooling impacts were consistent across cities with an average cooling impact of -0.187 K per increase of 0.01. While these interventions are broadly effective across cities, there are critical regional trade-offs between vegetation cooling efficiency, irrigation requirements, and the temporal duration and evolution of the cooling benefits. In warm, arid cities, high albedo surfaces offer multifaceted benefits such as cooling and water conservation, whereas temperate, mesic cities likely benefit from a combination of strategies, with greening efforts targeting highly paved neighborhoods.

Mapping the gaps between cooling benefits of urban greenspace and population heat vulnerability.

We provide a novel method to assess the heat mitigation impacts of greenspace though studying the mechanisms of ecosystems responsible for benefits and connecting them to heat exposure metrics. We demonstrate how the ecosystem services framework can be integrated into current practices of environmental health research using supply/demand state-of-the-art methods of ecological modeling of urban greenspace. We compared the supply of cooling ecosystem services in Boston measured through an indicator of high resolution evapotranspiration modeling, with the demand for benefits from cooling measured as a heat exposure risk score based on exposure, hazard and population characteristics. The resulting evapotranspiration indicator follows a pattern similar to conventional greenspace indicators based on vegetation abundance, except in warmer areas such as those with higher levels of impervious surface. We identified demand-supply mismatch areas across the city of Boston, some coinciding with affordable housing complexes and long term care facilities. This novel ES-framework provides cross-disciplinary methods to prioritize urban areas where greenspace interventions can have the most impact based on heat-related demand.

The innate immune molecule, NOD1, regulates direct killing of Helicobacter pylori by antimicrobial peptides.

The cytosolic innate immune molecule, NOD1, recognizes peptidoglycan (PG) delivered to epithelial cells via the Helicobacter pylori cag pathogenicity island (cagPAI), and has been implicated in host defence against cagPAI(+)H. pylori bacteria. To further clarify the role of NOD1 in host defence, we investigated NOD1-dependent regulation of human beta-defensins (DEFBs) in two epithelial cell lines. Our findings identify that NOD1 activation, via either cagPAI(+) bacteria or internalized PG, was required for DEFB4 and DEFB103 expression in HEK293 cells. To investigate cell type-specific induction of DEFB4 and DEFB103, we generated stable NOD1'knockdown' (KD) and control AGS cells. Reporter gene assay and RT-PCR analyses revealed that only DEFB4 was induced in an NOD1-/cagPAI-dependent fashion in AGS cells. Moreover, culture supernatants from AGS control, but not AGS NOD1 KD cells, stimulated with cagPAI(+)H. pylori, significantly reduced H. pylori bacterial numbers. siRNA studies confirmed that human beta-defensin 2 (hBD-2), but not hBD-3, contributes to the antimicrobial activity of AGS cell supernatants against H. pylori. This study demonstrates, for the first time, the involvement of NOD1 and hBD-2 in direct killing of H. pylori bacteria by epithelial cells and confirms the importance of NOD1 in host defence mechanisms against cagPAI(+)H. pylori infection.

Influence of landscape management practices on urban greenhouse gas budgets.

BACKGROUND: With a lack of United States federal policy to address climate change, cities, the private sector, and universities have shouldered much of the work to reduce carbon dioxide (CO2) and other greenhouse gas emissions. This study aims to determine how landcover characteristics influence the amount of carbon (C) sequestered and respired via biological processes, evaluating the role of land management on the overall C budget of an urban university. Boston University published a comprehensive Climate Action Plan in 2017 with the goal of achieving C neutrality by 2040. In this study, we digitized and discretized each of Boston University's three urban campuses into landcover types, with C sequestration and respiration rates measured and scaled to provide a University-wide estimate of biogenic C fluxes within the broader context of total University emissions. RESULTS: Each of Boston University's three highly urban campuses were net sources of biogenic C to the atmosphere. While trees were estimated to sequester 0.6 ± 0.2 kg C m-2 canopy cover year-1, mulch and lawn areas in 2018 emitted C at rates of 1.7 ± 0.4 kg C m-2 year-1 and 1.4 ± 0.4 kg C m-2 year-1, respectively. C uptake by tree canopy cover, which can spatially overlap lawn and mulched landcovers, was not large enough to offset biogenic emissions. The proportion of biogenic emissions to Scope 1 anthropogenic emissions on each campus varied from 0.5% to 2%, and depended primarily on the total anthropogenic emissions on each campus. CONCLUSIONS: Our study quantifies the role of urban landcover in local C budgets, offering insights on how landscaping management strategies-such as decreasing mulch application rates and expanding tree canopy extent-can assist universities in minimizing biogenic C emissions and even potentially creating a small biogenic C sink. Although biogenic C fluxes represent a small fraction of overall anthropogenic emissions on urban university campuses, these biogenic fluxes are under active management by the university and should be included in climate action plans.

Maximal Exercise Testing Using the Incremental Shuttle Walking Test Can Be Used to Risk-Stratify Patients with Pulmonary Arterial Hypertension.

Rationale: Exercise capacity predicts mortality in pulmonary arterial hypertension (PAH), but limited data exist on the routine use of maximal exercise testing.Objectives: This study evaluates a simple-to-perform maximal test (the incremental shuttle walking test) and its use in risk stratification in PAH.Methods: Consecutive patients with pulmonary hypertension were identified from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) registry (2001-2018). Thresholds for levels of risk were identified at baseline and tested at follow-up, and their incorporation into current risk stratification approaches was assessed.Results: Of 4,524 treatment-naive patients with pulmonary hypertension who underwent maximal exercise testing, 1,847 patients had PAH. A stepwise reduction in 1-year mortality was seen between levels 1 (≤30 m; 32% mortality) and 7 (340-420 m; 1% mortality) with no mortality for levels 8-12 (≥430 m) in idiopathic and connective tissue disease-related PAH. Thresholds derived at baseline of ≤180 m (>10%; high risk), 190-330 m (5-10%; intermediate risk), and ≥340 m (<5%; low risk of 1-yr mortality) were applied at follow-up and also accurately identified levels of risk. Thresholds were incorporated into the REVEAL (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management) 2.0 risk score calculator and French low-risk approach to risk stratification, and distinct categories of risk remained.Conclusions: We have demonstrated that maximal exercise testing in PAH stratifies mortality risk at baseline and follow-up. This study highlights the potential value of the incremental shuttle walking test as an alternative to the 6-minute walking test, combining some of the advantages of maximal exercise testing and maintaining the simplicity of a simple-to-perform field test.

Erectile dysfunction - when tablets don't work.

BACKGROUND: Erectile dysfunction (ED) is a common clinical problem managed in the general practice setting. While the majority of men will find phosphodiesterase-5 (PDE-5) inhibitors effective, there is a subgroup of men who require second and third line therapies. OBJECTIVE: This article provides an overview of ED and its management with particular focus on the group of patients in whom oral agents fail. DISCUSSION: Erectile dysfunction is a multifactorial condition that affects approximately 40% of Australian men. The incidence of ED is age related however, it shares common risk factors with cardiovascular disease and metabolic disorders. The management of ED should begin with an assessment of cardiovascular risk factors, advice on lifestyle modification, and a trial of PDE-5 inhibitors. Second line therapies include intracavernosal injections and vacuum erection devices, while third line therapy entails penile implants. Factors that influence treatment success include partner inclusion, good patient selection, as well as ongoing support and education.

Current and future biomass carbon uptake in Boston's urban forest.

Ecosystem services provided by urban forests are increasingly included in municipal-level responses to climate change. However, the ecosystem functions that generate these services, such as biomass carbon (C) uptake, can differ substantially from nearby rural forest. In particular, the scaled effect of canopy spatial configuration on tree growth in cities is uncertain, as is the scope for medium-term policy intervention. This study integrates high spatial resolution data on tree canopy and biomass in the city of Boston, Massachusetts, with local measurements of tree growth rates to estimate the magnitude and distribution of annual biomass C uptake. We further project C uptake, biomass, and canopy cover change to 2040 under alternative policy scenarios affecting the planting and preservation of urban trees. Our analysis shows that 85% of tree canopy area was within 10 m of an edge, indicating essentially open growing conditions. Using growth models accounting for canopy edge effects and growth context, Boston's current biomass C uptake may be approximately double (median 10.9 GgC yr-1, 0.5 MgC ha-1 yr-1) the estimates based on rural forest growth, much of it occurring in high-density residential areas. Total annual C uptake to long-term biomass storage was equivalent to <1% of estimated annual fossil CO2 emissions for the city. In built-up areas, reducing mortality in larger trees resulted in the highest predicted increase in canopy cover (+25%) and biomass C stocks (236 GgC) by 2040, while planting trees in available road margins resulted in the greatest predicted annual C uptake (7.1 GgC yr-1). This study highlights the importance of accounting for the altered ecosystem structure and function in urban areas in evaluating ecosystem services. Effective municipal climate responses should consider the substantial fraction of total services performed by trees in developed areas, which may produce strong but localized atmospheric C sinks.

Postprostatectomy stress urinary incontinence - Current and evolving therapies.

BACKGROUND: Postprostatectomy stress urinary incontinence (PPSUI) is a clinically significant problem with an incidence of 3-60%. OBJECTIVE: This article discusses the indications and efficacy of current and evolving surgical therapies for PPSUI as a guide for general practitioners. DISCUSSION: Surgical intervention can be considered for bothersome PPSUI persisting longer than 12 months for which conservative therapy has failed. Careful preoperative assessment and counselling is necessary to select appropriate candidates for surgical intervention. When considering the success of various therapies for PPSUI, patient satisfaction is often related to the magnitude of incontinence pad reduction, rather than absolute pad usage per day. Currently, there are several surgical therapies available for PPSUI including bulking agents, the artificial urinary sphincter (AUS-800) and male sling devices. The AUS-800 remains the gold standard for moderate to severe PPSUI, however, sling devices demonstrate promising short to intermediate term results.

Live fast, die young: Accelerated growth, mortality, and turnover in street trees.

Municipalities are embracing greening initiatives as a key strategy for improving urban sustainability and combatting the environmental impacts of expansive urbanization. Many greening initiatives include goals to increase urban canopy cover through tree planting, however, our understanding of street tree ecosystem dynamics is limited and our understanding of vegetation structure and function based on intact, rural forests does not apply well to urban ecosystems. In this study, we estimate size-specific growth, mortality, and planting rates in trees under municipal control, use a box model to forecast short-term changes in street tree aboveground carbon pools under several planting and management scenarios, and compare our findings to rural, forested systems. We find accelerated rates of carbon cycling in street trees with mean diameter growth rates nearly four times faster in Boston, MA, USA (0.78 ± 0.02 cm yr-1) than in rural forest stands of MA (0.21 ± 0.02 cm yr-1) and mean mortality rates more than double rural forested rates (3.06 ± 0.25% yr-1 in street trees; 1.41 ± 0.04% yr-1 in rural trees). Despite the enhanced growth of urban trees, high mortality losses result in a net loss of street tree carbon storage over time (-0.15 ± 0.09 Mg C ha-1 yr-1). Planting initiatives alone may not be sufficient to maintain or enhance canopy cover and biomass due to the unique demographics of urban ecosystems. Initiatives to aid in the establishment and preservation of tree health are central for increasing street tree canopy cover and maintaining/increasing carbon storage in vegetation. Strategic combinations of planting and maintenance will maximize the viability of greening initiatives as an effective climate mitigation tool.

The incremental shuttle walk test predicts mortality in non-group 1 pulmonary hypertension: results from the ASPIRE Registry.

Pulmonary hypertension (PH) is classified into five groups based on disease etiology but there is only limited information on the prognostic value of exercise testing in non-group 1 PH. In group 1 PH, the incremental shuttle walking test (ISWT) distance has been shown to correlate with pulmonary hemodynamics and predict survival without a ceiling effect. This study assessed the ISWT in non-group 1 PH. Data were retrieved from the ASPIRE Registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) for consecutive patients diagnosed with PH. Patients were required to have been systematically assessed as group 2-5 PH and to have a baseline ISWT within three months of cardiac catheterization. Patients were stratified according to incremental shuttle walk test distance (ISWD) and ISWT distance percent predicted (ISWD%pred). A total of 479 patients with non-group 1 PH were identified. ISWD and ISWD%pred correlated significantly with symptoms and hemodynamic severity. ISWD and ISWD%pred predicted survival with no ceiling effect. The test was prognostic in groups 2, 3, and 4. ISWD and ISWD%pred and change in ISWD and ISWD%pred at one year were all significant predictors of outcome. In patients with non-group 1 PH the ISWT is a simple non-invasive test that is easy to perform, is predictive of survival at baseline and follow-up, reflects change, and can be used in the assessment of PH of any etiology.

Incremental Shuttle Walking Test Distance Is Reduced in Patients With Pulmonary Hypertension in World Health Organisation Functional Class I.

Background: There is increasing interest in screening for and diagnosing pulmonary hypertension earlier in the course of disease. However, there is limited data on cardiopulmonary abnormalities in patients with pulmonary hypertension newly diagnosed in World Health Organization Function Class (WHO FC) I. Methods: Data were retrieved from the ASPIRE registry (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral center) for consecutive treatment naïve patients diagnosed with pulmonary hypertension by cardiac catheterization between 2001 and 2010 who underwent incremental shuttle walk exercise testing. Results: Eight hundred and ninety-five patients were diagnosed with Group 1-5 pulmonary hypertension. Despite the absence of symptoms, patients in WHO FC I (n = 9) had a significant reduction in exercise capacity (Incremental shuttle walk distance percent predicted (ISWD%pred) 65 ± 13%, Z score -1.77 ± 1.05), and modest pulmonary hypertension with a median (interquartile range) pulmonary artery pressure 31(20) mmHg and pulmonary vascular resistance 2.1(8.2) Wood Units, despite a normal diffusion of carbon monoxide adjusted for age and sex (DLco)%pred 99 ± 40%. Compared to patients in WHO FC I, patients in WHO FC II (n = 162) had a lower ISWD%pred 43 ± 22 and lower DLco%pred 65 ± 21%. Conclusion: Our results demonstrate that patients with newly diagnosed pulmonary hypertension with no or minimal symptomatic limitation have a significant reduction of exercise capacity.

Incremental shuttle walk test distance and autonomic dysfunction predict survival in pulmonary arterial hypertension.

BACKGROUND: To ensure effective monitoring of pulmonary arterial hypertension (PAH), a simple, reliable assessment of exercise capacity applicable over a range of disease severity is needed. The aim of this study was to assess the ability of the incremental shuttle walk test (ISWT) to correlate with disease severity, measure sensitivity to change, and predict survival in PAH. METHODS: We enrolled 418 treatment-naïve patients with PAH with baseline ISWT within 3 months of cardiac catheterization. Clinical validity and prognostic value of ISWT distance were assessed at baseline and 1 year. RESULTS: ISWT distance was found to correlate at baseline with World Health Organization functional class, Borg score, and hemodynamics without a ceiling effect (all p < 0.001). Walking distance at baseline and after treatment predicted survival; the area under the receiver operating characteristic curve for ability of ISWT distance to predict mortality was 0.655 (95% confidence interval 0.553-0.757; p = 0.004) at baseline and 0.737 (95% confidence interval 0.643-0.827; p < 0.001) at 1 year after initiation of treatment. Change in ISWT distance also predicted survival (p = 0.04). Heart rate (HR) and systolic blood pressure (SBP) parameters reflecting autonomic response to exercise (highest HR, change in HR, HR recovery at 1 minute >18 beats/min, highest SBP, change in SBP, and 3-minute SBP ratio) were significant predictors of survival (all p < 0.05). CONCLUSIONS: In patients with PAH, the ISWT is simple to perform, allows assessment of maximal exercise capacity, is sensitive to treatment effect, predicts outcome, and has no ceiling effect. Also, measures of autonomic function made post-exercise predict survival in PAH.

Opening the ICU doors.

Family member presence may contribute to the healing of hospitalized patients, but may also be in conflict with the perceived needs of delivering intensive care. We detail our experience with "opening the doors" of the intensive care unit (ICU), allowing family members to be present and participate in the care of loved ones without restriction. "Opening the doors" challenged the traditions, legacy and sense of professional entitlement that were a part of ICU culture and generated considerable initial resistance among nurses and physicians. We describe our "opening the doors" transformation to more patient- and family-centered care in four steps: (1) enlist support of administrative and local leaders; (2) create a collective aim; (3) test on a small scale, and (4) scale up after initial successes. Preparing ICU staff so that they are comfortable with more "on stage" time (i.e., greater family presence) was critical to our success. "Opening the doors" now serves as a guiding vision to organizing the ICU's work.

Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila.

Legionella pneumophila (Lp), an important cause of morbidity and mortality from pneumonia, infects alveolar macrophages (AMs) and is recognized by several TLRs as well as Birc1e (NAIP5) and IL-1 converting enzyme-protease activating factor. We examined the role of TLR5 during the murine response to aerosolized Lp infection. At 4 h after infection, Tlr5(-/-) mice had lower numbers of polymorphonuclear neutrophils (PMNs) in their broncho-alveolar lavage fluid in comparison to wild-type (WT) mice. At 24 and 72 h, the PMN recruitment was similar. WT mice infected with a flagellin-deficient strain (LpFlaA-) also showed an impaired early PMN response at 4 h compared with those infected with the WT strain. There was no consistent difference in bacterial counts at any of the time points when comparing the Tlr5(-/-) and WT mice. However, at 6 days after infection, the Tlr5(-/-) mice had increased leukocytic infiltrates in the alveolar and peribronchial interstitial spaces that were consistent with organizing pneumonia. We also examined the role of TLR5 during macrophage infection. In contrast to bone marrow-derived macrophages, AMs secreted TNF-alpha after stimulation with purified flagellin. In addition, WT, but not Tlr5(-/-), AMs produced TNF-alpha after stimulation with Lp. Live LpFlaA- did not induce TNF-alpha secretion in AM. These results suggested that AMs recognize Lp flagellin and that a majority of the Lp-induced TNF-alpha response is TLR5-mediated. Thus, TLR5 mediates recognition of Lp in AMs and performs a distinct role during the in vivo pulmonary immune response through regulation of early PMN recruitment and subsequent later development of pneumonia.

Proteomic tracking of serum protein isoforms as screening biomarkers of ovarian cancer.

Epithelial ovarian cancer is the fourth leading cause of cancer death among women. Due to the asymptomatic nature and poor survival characteristic of the disease, screening for specific biomarkers for ovarian cancer is a major health priority. Differentially expressed proteins in the serum of ovarian cancer patients have the potential to be used as cancer-specific biomarkers. In this study, proteomic methods were used to screen 24 serum samples from women with high-grade ovarian cancer and compared to a control group of 11 healthy women. Affigel-Blue treated serum samples were processed either by linear (pH 4-7) or narrow range (pH 5.5-6.7) IEF strips for the first dimension. Proteins separated in first dimension were resolved by 8-16% gradient SDS-PAGE. Protein spots were visualized by SYPRO Ruby staining, imaged by FX-imager and compared and analyzed by PDQuest software. Twenty-two protein spots were consistently differentially expressed between normal and ovarian cancer patients by resolving proteins in a linear pH strip of 4-7 for the first dimension. Six of the protein spots, significantly up-regulated in grade 3 ovarian cancer patients (p < 0.05), were identified by MALDI-TOF MS and Western blotting as the isoforms of haptoglobin precursor. When serum proteins were resolved on narrow pH range strips (5.5-6.7), 23 spots were consistently differentially expressed between normal and grade 3 ovarian cancer patients. Of these, 4 protein spots significantly down regulated in grade 3 ovarian cancer patients (p < 0.05) were identified by MALDI-TOF MS and Western blotting, as isoforms of transferrin precursor. Increased expression of serum haptoglobin and transferrin was also identified in peritoneal tumor fluid obtained from women diagnosed with grade 2/3 ovarian cancer (n = 7). Changes in the expression of haptoglobin and transferrin in the serum of women with different pathological grades of ovarian cancer was examined by one-dimensional Western blotting method. Serum samples collected from women suffering from benign, borderline, grade 1, grade 2 and grade 3 cancer (n = 4 for haptoglobin and n = 5 for transferrin in each group) were analyzed and compared to the serum of normal healthy women. The mean serum haptoglobin expression in grade 3 ovarian cancer patients was fourfold higher than in the control subjects (p < 0.05). On the other hand, transferrin expression in grade 3 ovarian cancer patients was decreased by twofold than in normal healthy women (p < 0.05). Haptoglobin expression in the serum of cancer patients (n = 7) decreased following chemotherapy (six cycles of taxol/carboplatin). Concomitant with the decrease of haptoglobin, transferrin expression remained constant in four patients, but increased in three out of seven patients included in the study. Changes in serum expression of haptoglobin correlated with the change of CA 125 levels before and after chemotherapy. In conclusion, proteomic profiling of differentially expressed proteins in the sera of normal women compared to women with ovarian cancer can greatly facilitate the discovery of a panel of biomarkers that may aid in the detection of ovarian cancer with greater specificity.