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Abstract Large amounts of ultra-high molecular weight hyaluronan (HA) have been described as the main cause of cancer resistance in naked mole-rats (Heterocephalus glaber, NMR). Our work examined HA metabolism in these rodents more closely. HA was localized and quantified using HA binding proteins. Its molecular weight was determined using size exclusion chromatography and gel electrophoresis, HA family gene expression using RNAseq analysis, and hyaluronidase activity using zymography. Guinea pigs (Cavia porcellus) and mice (Mus musculus) were used as controls for some experiments. We found that HA localization was similar in NMR, guinea pig, and mouse tissues but NMR had larger amounts and higher molecular weight (maximum, around 2.5 MDa) of HA in serum and almost all tissues tested. We could not find ultra-high molecular weight HA (≥ 4 MDa) in NMR samples, in contrast to previous descriptions. Hyaluronidase-1 had lower expression and activity in NMR than mouse lymph nodes. RNAseq results showed that, among HA family genes, Tnfaip6 and hyaluronidase-3 (Hyal3) were systematically overexpressed in NMR tissues. In conclusion, NMR samples, contrary to expectations, do not harbor ultra-high molecular weight HA, although its amount and average molecular weight are higher in NMR than in guinea pig tissues and serum. Although hyaluronidase expression and activity are lower in NMR than mouse lymph nodes, this not sufficient to explain the presence of high molecular weight HA. A different activity of the NMR HA synthases remains possible. These characteristics, together with extremely high Hyal3 and Tnfaip6 expression, may provide the NMR with a bespoke, and perhaps protective, HA metabolism.

Abstract Background To evaluate the outcome of patients treated with stereotactic ablative body radiotherapy (SABR) with curative intent for stage I non-small cell lung cancer (NSCLC) with regard to local, regional and distant tumor control, disease-free survival (DFS), overall survival (OS) and toxicity. Methods Data of 300 patients treated with SABR for NSCLC cancer for the period of November 2007 to June 2016 were retrospectively analyzed. Of which, 189 patients had single primary lung lesion and were included in the study. The prescribed dose for the tumor was 48 Gy, given in 12 Gy × 4 fractions for all patients. In 2010, an improved protocol was established in advanced technology for the planning CT, dose calculation and imaging. Cumulative incidence function (CIF) of local, regional, distant or any recurrences were computed using competing risk analysis with death as a competing event. Survivals (DFS and OS) were estimated using the Kaplan-Meier method and Cox proportional regression was used for comparisons. Toxicities were graded according to the common terminology criteria for adverse events version 4.0 (CTCAE v.4). Results Diagnosis was histologically confirmed in 42% of the patients (N = 80). At 1, 2 and 4 years, the cumulative incidence function (CIF) of local relapses were 8% [4–13%], 15% [10–21%] and 18% [12–25%], the CIF of regional relapses were 4% [2–8%], 10% [6–16%] and 12% [8–19%], the CIF of distant relapses were 9% [5–14%], 15% [11–22%] and 20% [15–28%] and the CIF of any relapses were 14% [10–20%], 28% [22–36%], 34% [27–43%], respectively. After 1, 2 and 4 years, the OS rates were 83% [95% CI: 78–89%] (N = 128), 65% [95% CI: 57–73%] (N = 78) and 37% [95% CI: 29–47%] (N = 53), respectively. The median survival time was 37 months. The DFS after 1, 2 and 4 years reached 75% [95% CI: 68–81%] (N = 114), 49% [95% CI: 42–58%] (N = 60) and 31% [95% CI: 24–41%] (N = 41), respectively. No grade 4 or 5 toxicity was observed. Conclusions We observed a long-term local control and survival after SABR for peripheral stage I NSCLC in this large series of patients with the expected low toxicity.

Abstract Background Elderly patients are at high risk for postoperative complications and increased mortality after hip fracture (HF) surgery due to frailty and co-morbidities. The prediction of postoperative outcome could be used for clinical decision making. A reliable score to predict postoperative mortality after HF surgery in this sub-population remains unavailable. Methods A single-centre retrospective cohort study was performed in 782 patients who were operated on for HF. Receiver Operating Characteristic (ROC)-curves were used to analyse the performance of gender, age, neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) at admission (D0) as prognostic factors, alone or combined with the PreOperative Score to predict PostOperative Mortality (POSPOM) in univariate and multivariate linear regression models. Results No correlation between gender, age, NLR D0 or CRP D0 and postoperative, intra-hospital mortality was found. The Area Under the ROC-curve (AUC) for age, male gender, NLR and CRP were 0.61 [95% confidence interval (CI) = 0.45–0.61], 0.56 [95% CI = 0.42–0.56], 0.47 [95% CI = 0.29–0.47] and 0.49 [95% CI = 0.31–0.49] respectively. Combination with the POSPOM score did not increase its discriminative capacity as neither age (AUC = 0.69, 95% CI = 0.54–0.69), gender (AUC = 0.72, 95% CI = 0.58–0.72), NLR D0 (AUC = 0.71, 95% CI = 0.56–0.71), nor the CRP D0 (AUC = 0.71, 95% CI = 0.58–0.71) improved the POSPOM performance. Conclusions Neither age, gender, NLR D0 nor CRP D0 are suitable parameters to predict postoperative, intra-hospital mortality in elderly patients undergoing surgery for HF.

Abstract Background Among older couples, spouses are first in line to provide care, and they are key elements in the home support of dependent older persons. In this context, ensuring the health of these older spousal caregivers should be an important issue for all of the providers who care for older adults. The aim of this study was to longitudinally assess the health of older spousal caregivers considering frailty, nutrition, cognition, physical performance and mood disorders. Methods In this longitudinal, observational cohort study, participants were assessed at home in Wallonia, Belgium. At baseline, 82 community-dwelling spouses of older patients with cognitive deficits or functional impairment were assessed; 78 caregivers were assessed at follow-up (16 months). The clinical instruments used included Frailty Phenotype (Fried), the Mini Nutritional Assessment-short form (MNA-SF), Short Physical Performance Battery (SPPB), Geriatric Depression Scale (GDS-15), clock drawing test, medications, Zarit Burden Index (ZBI), and Caregiver Reaction Assessment (CRA). Biological assessments included plasma interleukin-6 (IL-6), ultrasensitive C-reactive protein (CRP), cortisol, albumin and insulin growth factor-1 (IGF-1). Results Among caregivers, 54% were women, and the mean age was 80 years. Among care-receivers, 83% had cognitive impairment. Caregivers were more likely to be in a pre-frail stage. In one-third of the caregivers, the frailty status worsened. Transitions were observed between each of the states, except from frail to robust. In contrast to frailty, items including nutrition, cognitive status, SPPB and mood assessments were stable over time, with approximately 70% of the caregivers not experiencing significant change at follow-up. Caregiver experiences assessed with the Zarit Burden Interview and CRA were relatively stable over 16 months. Conclusion Many caregivers of geriatric patients are spouses who are old themselves. A failure in the health of the caregiver may anticipate an undesired care breakdown. Caregiver health and its determinants should be explored in future longitudinal studies that cover a longer time period.