Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid ...tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.
Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR.
Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52).
Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.
One of the aims of the BCool programme is to search for cycles in other stars and to understand how similar they are to the Sun. In this paper, we aim to monitor the evolution of τ Boo's large-scale ...magnetic field using high-cadence observations covering its chromospheric activity maximum. For the first time, we detect a polarity switch that is in phase with τ Boo's 120-day chromospheric activity maximum and its inferred X-ray activity cycle maximum. This means that τ Boo has a very fast magnetic cycle of only 240 days. At activity maximum τ Boo's large-scale field geometry is very similar to the Sun at activity maximum: it is complex and there is a weak dipolar component. In contrast, we also see the emergence of a strong toroidal component which has not been observed on the Sun, and a potentially overlapping butterfly pattern where the next cycle begins before the previous one has finished.
•Introduction of immunotherapy did not change quality of care between hospitals.•Patients underrepresented in trials received immunotherapy in routine practice.•Patients with brain metastases ...survived as long as those without this disorder.•Patients with selected auto immune disorders survived longer.
Phase III studies of checkpoint inhibitors changed the therapeutic landscape for lung cancer. In 2015 the Dutch Society of Chest Physicians (NVALT) introduced a national immunotherapy registry for patients with lung cancer; quality standards for hospitals were implemented. At population level we studied clinical benefit in daily practice and in patients who are underrepresented in phase III trials.
From the initial introduction of checkpoint inhibitors in the Netherlands patients were centrally registered. Educational programs and quality control were provided under supervision of NVALT. The largest immunotherapy providing hospitals were compared to hospitals who provided less checkpoint inhibitors as marker of experience. Patients characteristics, treatment and side effects, response rate and survival were studied.
A total of 2676 patients were registered, 2302 with follow up data were evaluated. Between October 2015 and December 2017 a gradual increase from 12 to 30 qualified hospitals showed no major toxicity differences. Toxicity led to a hospital admission rate of 9.1 with an average duration of 10.4 days.
Overall tumor response was 21.8 % and median overall survival 12.6 months. Overall survival was not significantly different for patients aged ≥ 75 years, those having brain metastases or selected auto-immune diseases before start checkpoint inhibitors compared to younger patients or those without, respectively. Survival outcomes were worse in patients with PS 2+, non-smokers, and patients who received any palliative radiotherapy (HR 2.1, 95 % CI 1.7–2.7; 1.3, 95 % CI 1.0–1.6 and 1.2, 95 % CI 1.1–1.4, respectively).
Changes in the therapeutic landscape did not lead to major differences in quality of care between hospitals. Elderly patients, those with brain metastases or selected auto-immune disease underrepresented in clinical trials did not do worse on checkpoint inhibitors, except for those with PS 2 + .
Objectives
The link between skeletal muscle and heart disease remains intriguing. It is unknown how skeletal muscle may be associated with aspects of myocardial structure and function, particularly ...in the presence of aging‐related sarcopenia. We hypothesize that among aging adults with sarcopenia, alterations in myocardial structure and/or function may exist, resulting in a syndrome of “cardio‐sarcopenia.”
Methods
Participants derived from a community cohort study underwent same‐day bioimpedance body composition analysis that measured skeletal muscle in sites such as the trunk, upper limb, and lower limb, and echocardiography for assessment of myocardial structure and function. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria.
Results
We studied a total of 378 participants, of whom 88 (23.3%) had sarcopenia. Participants with sarcopenia had smaller left ventricular (LV) sizes (lower LV internal diameter end diastole (4.1 ± .7 vs 4.5 ± .6 cm; P < .0001), lower LV internal diameter end systole (2.3 ± .5 vs 2.5 ± .4 cm; P = .010), lower LV posterior wall end diastole (.7 ± .1 vs .8 ± .1 cm; P = .0036), and lower LV posterior wall end systole (1.4 ± .3 vs 1.5 ± .2 cm; P = .0031). Sarcopenic participants also had lower LV mass (106 ± 35 vs 126 ± 53; P = .0014) and lower left atrial (LA) volume (33 ± 13 vs 36 ± 13; P = .033). Adjusting for age and diabetes mellitus, skeletal muscle mass was associated with LV diameter (β = .06; 95% confidence interval CI = .03‐.09; P < .0001), LV mass (β = 4.04; 95% CI = 1.78‐6.29; P = .001), LA diameter (β = .05; 95% CI = .01‐.09; P = .007), and LA volume (β = 1.26; 95% CI = .38‐2.13; P = .005). A positive linear correlation was observed between LV mass and handgrip strength (r = .25; P < .0001).
Conclusion
Among a community sample of older adults with preserved heart function, sarcopenia is associated with reductions in LV and LA sizes. Skeletal muscle mass was independently associated with specific indices of myocardial structure. J Am Geriatr Soc 67:2568–2573, 2019
Background
In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases.
Objective
...We investigated whether CancerMath, a free online prediction tool for axillary lymph node involvement, is able to identify women at low risk of axillary lymph node metastases in Malaysian women with 3–5 cm tumors, with the aim to offer SNB in a targeted, cost-effective way.
Methods
Women with non-metastatic breast cancers, measuring 3–5 cm were identified within the University Malaya Medical Centre (UMMC) breast cancer registry. We compared CancerMath-predicted probabilities of lymph node involvement between women with versus without lymph node metastases. The discriminative performance of CancerMath was tested using receiver operating characteristic (ROC) analysis.
Results
Out of 1,017 patients, 520 (51 %) had axillary involvement. Tumors of women with axillary involvement were more often estrogen-receptor positive, progesterone-receptor positive, and human epidermal growth factor receptor (HER)-2 positive. The mean CancerMath score was higher in women with axillary involvement than in those without (53.5 vs. 51.3,
p
= 0.001). In terms of discrimination, CancerMath performed poorly, with an area under the ROC curve of 0.553 (95 % confidence interval CI 0.518–0.588). Attempts to optimize the CancerMath model by adding ethnicity and HER2 to the model did not improve discriminatory performance.
Conclusion
For Malaysian women with tumors measuring 3–5 cm, CancerMath is unable to accurately predict lymph node involvement and is therefore not helpful in the identification of women at low risk of node-positive disease who could benefit from SNB.
Objective. To describe the nature of bacteraemia in SLE patients and determine the short-term survival and long-term outcome of these patients. Methods. Analysis of the medical records of 1442 SLE ...patients who were regularly followed up in a tertiary teaching medical centre from 2000 to 2005. Results. Among 1442 SLE patients, 240 patients (17%) developed at least one episode of bacteraemia, corresponding to an incidence of 92.7 cases/1000 hospital admissions. Since SLE diagnosis, the overall survival of our patients was 92% at 5 yrs, 86% at 10 yrs and 79% at 15 yrs. However, after one episode of bacteraemia, the survival decreased to 76% at 30 days and 67% at 360 days. Of the 336 episodes of bacteraemia, 167 were community-acquired (49.7%) and 169 were nosocomial (50.3%). Staphylococcus aureus was the leading cause of Gram-positive bacteraemia. Among Gram-negative bacteria, non-typhoidal Salmonella and Escherichia coli were the most common species. Community-acquired Salmonella and Streptococcus bacteraemia were more common than nosocomial infections. Klebsiella and Acinetobacter spp. were significantly more responsible for nosocomial than community-acquired bacteraemia. Patients infected with Acinetobacter, Klebsiella or Pseudomonas had lower probabilities of 14-day survival (71.4, 55.6, 42.9%, respectively). Conclusions. Among SLE patients, an episode of bacteraemia was associated with an unfavourable long-term outcome. The bacterial species significantly influenced short-term survival. Therefore, when empiric antibiotic therapy is initiated in SLE patients who are suspected of bacteraemia, we suggest use of antibiotics that are effective against Pseudomonas, Klebsiella, Acinetobacter, S. aureus, and E. coli.
Electrochemical CO2 reduction (CO2R) is an attractive option for storing renewable electricity and for the sustainable production of valuable chemicals and fuels. In this roadmap, we review recent ...progress in fundamental understanding, catalyst development, and in engineering and scale-up. We discuss the outstanding challenges towards commercialization of electrochemical CO2R technology: energy efficiencies, selectivities, low current densities, and stability. We highlight the opportunities in establishing rigorous standards for benchmarking performance, advances in in operando characterization, the discovery of new materials towards high value products, the investigation of phenomena across multiple-length scales and the application of data science towards doing so. We hope that this collective perspective sparks new research activities that ultimately bring us a step closer towards establishing a low- or zero-emission carbon cycle.
Ge-doped silica fibre (GDSF) thermoluminescence dosimeters (TLD) are non-hygroscopic spatially high-resolution radiation sensors with demonstrated potential for radiotherapy dosimetry applications. ...The INTRABEAM® system with spherical applicators, one of a number of recent electronic brachytherapy sources designed for intraoperative radiotherapy (IORT), presents a representative challenging dosimetry situation, with a low keV photon beam and a desired rapid dose-rate fall-off close-up to the applicator surface. In this study, using the INTRABEAM® system, investigations were made into the potential application of GDSF TLDs for in vivo IORT dosimetry. The GDSFs were calibrated over the respective dose- and depth-range 1 to 20 Gy and 3 to 45 mm from the x-ray probe. The effect of different sizes of spherical applicator on TL response of the fibres was also investigated. The results show the GDSF TLDs to be applicable for IORT dose assessment, with the important incorporated correction for beam quality effects using different spherical applicator sizes. The total uncertainty in use of this type of GDSF for dosimetry has been found to range between 9.5% to 12.4%. Subsequent in vivo measurement of skin dose for three breast patients undergoing IORT were performed, the measured doses being below the tolerance level for acute radiation toxicity.
Autotrophic and heterotrophic organisms require resources in stoichiometrically balanced ratios of carbon (C) to nutrients, the demand for which links organismal and ecosystem-level biogeochemical ...cycles. In soils, the relative availability of C and nitrogen (N) also defines the strength of competition for ammonium between autotrophic nitrifiers and heterotrophic decomposers, which may influence the coupled dynamics between N mineralization and nitrification. Here, we use data from the publicly available US National Science Foundation funded Long Term Ecological Research (LTER) network to evaluate the influence of soil C concentration on the relationship between net nitrification and net N mineralization. We found that soil C availability constrains the fraction of mineralized N that is ultimately nitrified across the continental gradient, contributing to reduced rates of nitrification in soils with high C concentrations. Nitrate, which is produced by nitrification, is a highly mobile ion that easily leaches to aquatic ecosystems or denitrifies into the greenhouse gas nitrous oxide (N
2
O). Understanding the connection between soil C concentration and soil N transformations is thus important for managing potential ecosystem N losses, understanding the biogeochemical constraints of these losses, and accurately representing coupled C-N dynamics in ecosystem models.
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