Health-related quality of life with palbociclib plus endocrine therapy versus capecitabine in postmenopausal patients with hormone receptor–positive metastatic breast cancer: Patient-reported outcomes in the PEARL study

Background: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes. Patients and methods: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively. Results: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs. -2.1 for capecitabine (95% confidence interval [CI], 1.4–8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55–0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale. Conclusion: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated. Trial registration number: NCT02028507 (ClinTrials.gov). EudraCT study number: 2013-003170-27. © 2021 The Author(s

Neuromuscular Consequences of an Extreme Mountain Ultra-Marathon

We investigated the physiological consequences of one of the most extreme exercises realized by humans in race conditions: a 166-km mountain ultra-marathon (MUM) with 9500 m of positive and negative elevation change. For this purpose, (i) the fatigue induced by the MUM and (ii) the recovery processes over two weeks were assessed. Evaluation of neuromuscular function (NMF) and blood markers of muscle damage and inflammation were performed before and immediately following (n = 22), and 2, 5, 9 and 16 days after the MUM (n = 11) in experienced ultra-marathon runners. Large maximal voluntary contraction decreases occurred after MUM (−35% [95% CI: −28 to −42%] and −39% [95% CI: −32 to −46%] for KE and PF, respectively), with alteration of maximal voluntary activation, mainly for KE (−19% [95% CI: −7 to −32%]). Significant modifications in markers of muscle damage and inflammation were observed after the MUM as suggested by the large changes in creatine kinase (from 144±94 to 13,633±12,626 UI L−1), myoglobin (from 32±22 to 1,432±1,209 µg L−1), and C-Reactive Protein (from <2.0 to 37.7±26.5 mg L−1). Moderate to large reductions in maximal compound muscle action potential amplitude, high-frequency doublet force, and low frequency fatigue (index of excitation-contraction coupling alteration) were also observed for both muscle groups. Sixteen days after MUM, NMF had returned to initial values, with most of the recovery process occurring within 9 days of the race. These findings suggest that the large alterations in NMF after an ultra-marathon race are multi-factorial, including failure of excitation-contraction coupling, which has never been described after prolonged running. It is also concluded that as early as two weeks after such an extreme running exercise, maximal force capacities have returned to baseline

The Soft X-ray Imager (SXI) on the SMILE Mission

The Soft X-ray Imager (SXI) is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission. SMILE is a joint science mission between the European Space Agency (ESA) and the Chinese Academy of Sciences (CAS) and is due for launch in 2025. SXI is a compact X-ray telescope with a wide field-of-view (FOV) capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit. SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange (SWCX) process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere. SWCX provides a mechanism for boundary detection within the magnetosphere, such as the position of Earth’s magnetopause, because the solar wind heavy ions have a very low density in regions of closed magnetic field lines. The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours. SXI is led by the University of Leicester in the United Kingdom (UK) with collaborating organisations on hardware, software and science support within the UK, Europe, China and the United States

The Soft X-ray Imager (SXI) on the SMILE Mission

The Soft X-ray Imager (SXI) is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer (SMILE) mission. SMILE is a joint science mission between the European Space Agency (ESA) and the Chinese Academy of Sciences (CAS) and is due for launch in 2025. SXI is a compact X-ray telescope with a wide field-of-view (FOV) capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit. SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange (SWCX) process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere. SWCX provides a mechanism for boundary detection within the magnetosphere, such as the position of Earth’s magnetopause, because the solar wind heavy ions have a very low density in regions of closed magnetic field lines. The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours. SXI is led by the University of Leicester in the United Kingdom (UK) with collaborating organisations on hardware, software and science support within the UK, Europe, China and the United States

Transient hypophosphataemia associated with acute infectious disease in paediatric patients

The aim of this study was to investigate the prevalence of hypophosphataemia in children with acute infection and the relationship between serum phosphate and C-reactive protein (CRP) concentration. Serum phosphate and CRP levels were measured on admission in 238 patients (aged 1 month to 14 y) with: pneumonia (n = 51), upper respiratory tract-related bacterial infection (n = 70), urinary tract infection (n = 50) and viral infection (n = 67). Patients were classified according to CRP value (0-50, 51-100, 101-150, ≥ 151 mg/l) and type of infection. The prevalence of hypophosphataemia was calculated for each group. 30 children with hypophosphataemia on admission had serial measurements of serum phosphate and CRP levels. A significant negative correlation between serum phosphate and CRP levels was found (r = - 0.41, p &lt; 0.0001). Patients with CRP ≥ 151 mg/l on admission had a lower mean serum phosphate value than those with CRP ≤ 50 mg/l (1.17 vs 1.50 mmol/l, p &lt; 0.0001). The overall prevalence of hypophosphataemia for patients with pneumonia, upper respiratory tract bacterial infection, urinary tract and viral infections was 45%, 35.7%, 18% and 4.4%, respectively. Hypophosphataemia occurred during the phase of rising of CRP level and resolved soon after CRP reached a plateau. In conclusion, hypophosphataemia is a relatively frequent but transient phenomenon in children with acute infectious disease. It is associated with an increase in CRP concentration and resolves before the normalization of CRP levels

Circulating adiponectin in preterm infants fed Long-Chain Polyunsaturated Fatty Acids (LCPUFA)-supplemented formula - A randomized controlled study

Adiponectin has potent insulin-sensitizing effects, improves lipid metabolism, and potentially protects against the development of metabolic syndrome. Thus, increasing adiponectin levels in preterm infants at risk for developing metabolic syndrome may be of special interest. The aim of this study was to examine the effects of dietary long-chain polyunsaturated fatty acids (LCPUFA) on serum adiponectin and lipid concentrations in preterm infants. Adiponectin and lipid levels of 60 healthy preterm infants [gestational age 32.7 (1.9) wk] randomly assigned to be fed either 1) a formula containing LCPUFA [arachidonic and docosahexanoic] (+LCPUFA group) or 2) the same formula without LCPUFA (-LCPUFA/control group), were determined at mean (SD) 33.8 (11.7) d. Adiponectin and HDL-C concentrations were significantly higher in the +LCPUFA group than in controls (p = 0.002 and p = 0.01, respectively); whereas, triglyceride levels were lower (p = 0.06). Adiponectin correlated positively with HDL-C levels and negatively with triglyceride levels in the +LCPUFA group but not in the controls. In conclusion, circulating adiponectin concentrations were higher in preterm infants fed a formula containing LCPUFA than infants fed an LCPUFA-free formula and they correlated with lipidemic profile. © International Pediatrics Research Foundation, Inc. 2008. All Rights Reserved

Clinical value of serum amyloid-A protein, high-density lipoprotein cholesterol and apolipoprotein-A1 in the diagnosis and follow-up of neonatal sepsis

Background: To evaluate the performance of serum amyloid-A (SAA), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein-A1 (Apo-A1) levels in the identification and monitoring of neonatal sepsis. Methods: This prospective study included 113 full-term septic neonates (postnatal age 4-28 days) admitted to the Special Care Neonatal Unit of a University Hospital from January 1, 2016, to April 30, 2019, and 68 healthy neonates (controls). Blood samples were drawn serially in septic neonates at enrollment and on days 1, 3 and 7, and once in controls, for SAA, HDL-C and Apo-A1 determination. Results: At enrollment, SAA levels were significantly higher in septic neonates in comparison with controls (median 50.7 vs. 3.5 mg/L; P &lt; 0.0001); HDL-C and Apo-A1 levels were significantly lower in patients than in controls (P &lt; 0.001 and P &lt; 0.006, respectively). SAA levels were higher in culture-positive compared with culture-negative sepsis (median 202.0 vs. 14.2 mg/L; P &lt; 0.0001). HDL-C and Apo-A1 levels did not differ significantly between culture-positive and culture-negative sepsis. Receiver operating characteristic curve analysis of SAA levels at enrollment resulted in significant areas under the curve (AUC) for detecting sepsis {AUC = 0.929 [95% confidence interval: 0.885-0.973]; P &lt; 0.0001} and also for discriminating between culture-positive and culture-negative sepsis [AUC = 0.933 (95% confidence interval: 0.882-0.984); P &lt; 0.0001]. The combination of HDL-C and Apo-A1 with SAA increased its diagnostic performance. Furthermore, serial SAA levels following enrollment could indicate clinical response in septic neonates. Conclusions: SAA seems to be a useful biomarker for identification and monitoring of neonatal sepsis, and also for discriminating between culture-positive and culture-negative sepsis. HDL-C and Apo-A1 could be used as complementary markers. © 2020 Wolters Kluwer Health, Inc