Predicting In-Hospital Mortality in Patients Undergoing Percutaneous Coronary Intervention

Background Standardization of risk is critical in benchmarking and quality improvement efforts for percutaneous coronary interventions (PCI). In 2018, the CathPCI Registry was updated to include additional variables to better classify higher-risk patients. Objectives We sought to develop a model for predicting in-hospital mortality risk following PCI incorporating these additional variables. Methods Data from 706,263 PCIs performed between 7/2018-6/2019 at 1,608 sites were used to develop and validate a new full and pre-catheterization model to predict in-hospital mortality, and a simplified bedside risk score. The sample was randomly split into a development (70%, n=495,005) and validation cohort (30%, n=211,258). We created 1,000 bootstrapped samples of the development cohort and used stepwise selection logistic regression on each sample. The final model included variables that were selected in at least 70% of the bootstrapped samples and those identified a priori due to clinical relevance. Results In-hospital mortality following PCI varied based on clinical presentation. Procedural urgency, cardiovascular instability, and level of consciousness after cardiac arrest were most predictive of in-hospital mortality. The full model performed well, with excellent discrimination (c-index: 0.943) in the validation cohort and good calibration across different clinical and procedural risk cohorts. The median hospital risk-standardized mortality rate was 1.9% and ranged from 1.1% to 3.3% (interquartile range: 1.7%-2.1%). Conclusions The risk of mortality following PCI can be predicted in contemporary practice by incorporating variables that reflect clinical acuity. This model, which includes data previously not captured, is a valid instrument for risk stratification and for quality improvement efforts

Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis

Zn2+-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn2+-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential cofactor of the ATM kinase. Here we show that absence of ASCIZ leads to p53-independent late-embryonic lethality in mice. Asciz-deficient primary fibroblasts exhibit increased sensitivity to DNA base damaging agents MMS and H2O2, but Asciz deletion or knock-down does not affect ATM levels and activation in mouse, chicken, or human cells. Unexpectedly, Asciz-deficient embryos also exhibit severe respiratory tract defects with complete pulmonary agenesis and severe tracheal atresia. Nkx2.1-expressing respiratory precursors are still specified in the absence of ASCIZ, but fail to segregate properly within the ventral foregut, and as a consequence lung buds never form and separation of the trachea from the oesophagus stalls early. Comparison of phenotypes suggests that ASCIZ functions between Wnt2-2b/ß-catenin and FGF10/FGF-receptor 2b signaling pathways in the mesodermal/endodermal crosstalk regulating early respiratory development. We also find that ASCIZ can activate expression of reporter genes via its SQ/TQ-cluster domain in vitro, suggesting that it may exert its developmental functions as a transcription factor. Altogether, the data indicate that, in addition to its role in the DNA base damage response, ASCIZ has separate developmental functions as an essential regulator of respiratory organogenesis

Contributions of Long-Range and Regional Atmospheric Transport on Pesticide Concentrations Along a Transect Crossing a Mountain Divide.

Twenty-one halogenated legacy and current-use pesticides and pesticide degradation products were measured in pine needles along a coast-to-coast transect that crossed the Southern Alps of New Zealand. Concentration profiles of nine pesticides were used to determine the influence of geographic sources on the atmospheric pesticide burden at the mountain sites. Pesticide concentration profiles were calculated for each source and mountain site by normalizing concentrations (adjusted for temperature at the site and air–needle partitioning) to the sum of all pesticide concentrations at the site. Each mountain site profile was compared to varying mixtures of the potential source profiles to determine the percent contribution of each source. The highest elevation mountain sites were primarily influenced by long-range, synoptic-scale northwesterly winds. Westerly upslope winds had little influence on any of the mountain sites. Easterly upslope winds from the Canterbury Plains, an agricultural region, strongly influenced the mountain sites within close proximity and had progressively less influence with distance

Selective Pressurized Liquid Extraction of Halogenated Pesticides and Polychlorinated Biphenyls Form Pine Needles.

Pine needles are an ideal matrix for the long-term monitoring of semi-volatile organic compounds in the atmosphere because they are naturally occurring and distributed worldwide. However, typical extraction methods result in the co-elution of matrix-interfering compounds and thus require time-consuming clean-up steps. A selective pressurised liquid extraction method (S-PLE) for extracting current-use pesticides, historic-use pesticides and polychlorinated biphenyls (PCBs) from pine needles that does not require additional clean-up steps was developed and validated. The selective extraction was achieved by packing the extraction vessel with a fat retainer, Florisil, down-stream of the pine needle matrix. A fat to fat-retainer ratio of 0.0057 (corresponding to 35 g of Florisil per 10 g of pine needle sample) was selected to minimise the co-elution of matrix-interfering compounds. Three 5-min extractions were performed using 25:75 (v/v) dichloromethane:n-hexane and a solvent flush of 150%. The mean recovery of spiked current-use pesticides, historic-use pesticides and PCBs using this method was 71%, 72%, and 84%, respectively. The method was validated by comparing target analyte concentrations measured in a pine needle sample using the optimised S-PLE method to those obtained using a conventional PLE method with external clean-up. The method detection limits and reproducibility were similar for the two methods; however, sample preparation time was 67% shorter when using the S-PLE method

Trace elements and metal pollution in aerosols at an alpine site, New Zealand: sources, concentrations and implications

Atmospheric aerosol samples were collected at a remote site in New Zealand\u27s Southern Alps. Collected samples were found to be a mixture of New Zealand and Australian sourced sediment, using their trace element signatures. Aerosol concentrations and the relative contribution of different sources was found to be a function of specific air-mass trajectories influencing the study site, dust entrainment rates in source areas and rainfall. Results show that Australian dust is a major source of particulate matter in New Zealand, particularly in remote alpine locations; however, locally derived dust is also important. Metal pollutants, including Pb, Cu and Sn, were enriched in the samples by approximately 15 times and up to \u3e100 times expected natural concentrations, confirming that metal pollution is a ubiquitous component of the atmosphere, even in relatively remote locations. Moreover, pollutants were highly enriched in otherwise clean air, i.e. during and following rainfall. Additionally, high concentrations of elements naturally enriched in sea water, e.g. Sr, Ba and Rb, were deposited alongside mineral dust, reflecting the oceanic origin of air influencing the site and the role of sea spray in contributing aerosol to the atmosphere. These elements experienced the greatest enrichment during rainfall, implying sea spray and pollution become relatively important during otherwise clean air conditions

Using Trace Elements in Particulate Matter to Identify the Sources of Semi-Volatile Organic Contaminants in Air at an Alpine Site.

An approach using trace elements in particulate matter (PM) to identify the geographic sources of atmospherically transported semivolatile organic contaminants (SOCs) was investigated. Daily samples of PM and SOCs were collected with high-volume air samplers from 16 January to 16 February 2009 at Temple Basin, a remote alpine site in New Zealand’s Southern Alps. The most commonly detected pesticides were dieldrin, trans-chlordane, endosulfan I, and chlorpyrifos. Polycyclic aromatic hydrocarbons and polychlorinated biphenyls were also detected. For each sampling day, the relative contribution of PM from regional New Zealand versus long-range Australian sources was determined using trace element profiles and a binary mixing model. The PM approach indicated that endosulfan I, indeno[1,2,3-c,d]pyrene, and benzo[g,h,i]perylene found at Temple Basin were largely of Australian origin. Local wind observations indicated that the chlorpyrifos found at Temple Basin primarily came from the Canterbury Plains in New Zealand

Trace Elements and Metal Pollution in Aerosols at an Alpine Site, New Zealand: Sources, Concentrations, and Implications.

Atmospheric aerosol samples were collected at a remote site in New Zealand\u27s Southern Alps. Collected samples were found to be a mixture of New Zealand and Australian sourced sediment, using their trace element signatures. Aerosol concentrations and the relative contribution of different sources was found to be a function of specific air-mass trajectories influencing the study site, dust entrainment rates in source areas and rainfall. Results show that Australian dust is a major source of particulate matter in New Zealand, particularly in remote alpine locations; however, locally derived dust is also important. Metal pollutants, including Pb, Cu and Sn, were enriched in the samples by approximately 15 times and up to \u3e100 times expected natural concentrations, confirming that metal pollution is a ubiquitous component of the atmosphere, even in relatively remote locations. Moreover, pollutants were highly enriched in otherwise clean air, i.e. during and following rainfall. Additionally, high concentrations of elements naturally enriched in sea water, e.g. Sr, Ba and Rb, were deposited alongside mineral dust, reflecting the oceanic origin of air influencing the site and the role of sea spray in contributing aerosol to the atmosphere. These elements experienced the greatest enrichment during rainfall, implying sea spray and pollution become relatively important during otherwise clean air conditions

Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research to advance the health of people with inherited bleeding disorders with the potential to menstruate

BACKGROUND: People who have or had the potential to menstruate (PPM) with inherited bleeding disorders (BD) face particular challenges receiving appropriate diagnosis and care and participating in research. As part of an initiative to create a National Research Blueprint for future decades of research, the National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive all-stakeholder consultations to identify the priorities of PPM with inherited BDs and those who care for them. RESEARCH DESIGN AND METHODS: Working group (WG) 4 of the NHF State of the Science Research Summit distilled community-identified priorities for PPM with inherited BDs into concrete research questions and scored their feasibility, impact, and risk. RESULTS: WG4 identified important gaps in the foundational knowledge upon which to base optimal diagnosis and care for PPM with inherited BDs. They defined 44 top-priority research questions concerning lifespan sex biology, pregnancy and the post-partum context, uterine physiology and bleeding, bone and joint health, health care delivery, and patient-reported outcomes and quality-of-life. CONCLUSIONS: The needs of PPM will best be advanced with research designed across the spectrum of sex and gender biology, with methodologies and outcome measures tailored to this population, involving them throughout