Abstract We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods ...over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro . The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach. From the Clinical Editor The ability of gold nanoparticles (AuNPs) to enhance the effect of physical radiation dose on tumor cells is known. This radiosensitization effect is thought to result from an increased number of photoelectric absorption events and the increased number of electrons present in gold. The authors here sought to further increase the amount and specificity of gold accumulation in prostatic cancer cells by conjugating gold nanorods to goserelin, a synthetic luteinizing hormone releasing hormone (LHRH) analogue that would bind to the LHRH receptor overexpressed in prostate cancers. It was shown that tumour cells were more sensitive to megavoltage radiation therapy. It is hoped that there would be eventual clinical translation of this approach.
Cardiogenic shock from acute on chronic heart failure is a lethal condition that frequently requires temporary mechanical circulatory support devices (tMCS) as a bridge to stabilization, durable ...support, or heart transplantation. However, there are limited data on methods to optimize use of tMCS in this population. We identified patients who received tMCS devices for cardiogenic shock from acute on chronic heart failure at a single center from August 2016 to July 2020. All the patients had invasive hemodynamic data before and immediately after tMCS placement. We classified patients according to whether they showed stabilization or decompensation with tMCS. We then evaluated hemodynamics pre-tMCS, post-tMCS, and the change in hemodynamics with tMCS (∆-tMCS) and assessed their relationship with clinical outcomes. Among 111 patients who received tMCS, 71 stabilized, and 40 decompensated. Post-tMCS hemodynamics were more likely than were pre-tMCS or ∆-tMCS to predict stabilization. Post-tMCS cardiac index >2.1 (area under the curve: 92.2) and cardiac power index >0.3 (area under the curve: 89.6) were the best predictors of stabilization. Patients who decompensated had increased in-hospital all-cause mortality (hazard ratio 3.06 1.29 to 7.24, p = 0.011), cardiovascular mortality, and increased hospital and intensive care unit length of stay and were less likely to receive left ventricular assist device or heart transplant (hazard ratio 0.56 0.36 to 0.88, p = 0.01). In conclusion, among patients with cardiogenic shock from acute on chronic heart failure who received tMCS, post-tMCS cardiac index and cardiac power index were highly predictive of stabilization. Those who decompensated had increased mortality, hospital length of stay, and intensive care unit length of stay and were less likely to receive heart replacement therapy.
Adults age 65 and over are the fastest growing segment of the population in the United States and around the world. As the size of this population expands, the number of older adults referred for ...surgical procedures will continue to increase. Due to the physiologic changes of aging and the increased frequency of comorbidities, older adults are at increased risk for adverse outcomes, and perioperative care is inherently more complex than in younger individuals. In this review, we discuss the physiologic changes of aging relevant to the surgical patient, comprehensive preoperative assessment, and postoperative management of common complications in older adults in order to promote optimal clinical outcomes both perioperatively and long‐term.
Preoperative Echo: Overused or Undervalued? Wolfe, Natasha K.; Wolfe, Jonathan D.; Rich, Michael W.
Journal of the American Geriatrics Society,
August 2020, 2020-08-00, 20200801, Letnik:
68, Številka:
8
Journal Article
Recenzirano
Odprti dostop
See related Special Series On Orthogeriatrics by Sinvani et al. in this issue.
Randomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate ...this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19.
Clinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality.
1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31-0.72)).
The protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.
We compare equilibrium climate sensitivity (ECS) estimates from pairs of long (≥ 800‐year) control and abruptly quadrupled CO2 simulations with shorter (150, 300 year) coupled atmosphere‐ocean ...simulations and Slab Ocean Models (SOM). Consistent with previous work, ECS estimates from shorter coupled simulations based on annual averages for years 1‐150 underestimate those from SOM (‐8% ± 13%) and long (‐14% ± 8%) simulations. Analysis of only years 21‐150 improved agreement with SOM (‐2% ± 14%) and long (‐8% ± 10%) estimates. Use of pentadal averages for years 51‐150 results in improved agreement with long simulations (‐4% ± 11%). While ECS estimates from current generation US models based on SOM and coupled annual averages of years 1‐150 range from 2.6°C to 5.3°C, estimates based longer simulations of the same models range from 3.2°C to 7.0°C. Such variations between methods argues for caution in comparison and interpretation of ECS estimates across models.
The Energy Exascale Earth System Model (E3SM) is a new coupled Earth system model sponsored by the U.S Department of Energy. Here we present E3SM global simulations using active ocean and sea ice ...that are driven by the Coordinated Ocean‐ice Reference Experiments II (CORE‐II) interannual atmospheric forcing data set. The E3SM ocean and sea ice components are MPAS‐Ocean and MPAS‐Seaice, which use the Model for Prediction Across Scales (MPAS) framework and run on unstructured horizontal meshes. For this study, grid cells vary from 30 to 60 km for the low‐resolution mesh and 6 to 18 km at high resolution. The vertical grid is a structured z‐star coordinate and uses 60 and 80 layers for low and high resolution, respectively. The lower‐resolution simulation was run for five CORE cycles (310 years) with little drift in sea surface temperature (SST) or heat content. The meridional heat transport (MHT) is within observational range, while the meridional overturning circulation at 26.5°N is low compared to observations. The largest temperature biases occur in the Labrador Sea and western boundary currents (WBCs), and the mixed layer is deeper than observations at northern high latitudes in the winter months. In the Antarctic, maximum mixed layer depths (MLD) compare well with observations, but the spatial MLD pattern is shifted relative to observations. Sea ice extent, volume, and concentration agree well with observations. At high resolution, the sea surface height compares well with satellite observations in mean and variability.
Key Points
The Energy Exascale Earth System Model (E3SM) is a new climate model by the U.S. Department of Energy
E3SM ocean and ice components use unstructured horizontal meshes for variable‐resolution simulations
The 310‐year E3SM simulations agree well with observations in ocean currents and sea ice coverage
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