Single-fraction radiotherapy (SFRT) for bone metastases: Patient selection and perspectives

Bone metastases are a frequent and important source of morbidity in cancer patients. Stereotactic body radiation therapy (SBRT) is an established treatment option for local control and pain relief of bone metastases, and it is increasingly used as upfront treatment, postoperative consolidation or salvage treatment after prior RT. However, heterogeneity of dose schedules described in literature represents a severe limitation in the definition of the role of SBRT as a standard of care. No consensus is available on the use of single versus multiple fraction SBRT for bone metastases. Advantages of single-fraction SBRT include shorter overall duration of treatment, absence of inter-fraction uncertainty, improved compliance, theoretical increased efficacy, and lower costs. However, caution has been advised due to reports of severe late toxicities, in particular, vertebral collapse fracture (VCF). The aim of this paper is to review dose fractionation and indications for the management of bone metastases using SBRT

Reliability of low‐power cycling efficiency in energy expenditure phenotyping of inactive men and women

Standardized approaches to assess human energy expenditure (EE) are well defined at rest and at moderate to high‐intensity exercise, but not at light intensity physical activities energetically comparable with those of daily life (i.e., 1.5–4 times the resting EE, i.e., 1.5–4 METs). Our aim was to validate a graded exercise test for assessing the energy cost of low‐intensity dynamic work in physically inactive humans, that is, those who habitually do not meet the guidelines for moderate‐to‐vigorous aerobic physical activity levels. In healthy and inactive young men and women (n = 55; aged 18–32 years), EE was assessed in the overnight‐fasted state by indirect calorimetry at rest and during graded cycling between 5 and 50W for 5 min at each power output on a bicycle ergometer. Repeatability was investigated on three separate days, and the effect of cadence was investigated in the range of 40–90 rpm. Within the low power range of cycling, all subjects perceived the exercise test as “light” on the Borg scale, the preferred cadence being 60 rpm. A strong linearity of the EE‐power relationship was observed between 10 and 50 W for each individual (r > 0.98), and the calculation of delta efficiency (DE) from the regression slope indicated that DE was similar in men and women (~29%). DE showed modest inter‐individual variability with a coefficient of variation (CV) of 11%, and a low intra‐individual variability with a CV of ~ 5%. No habituation or learning effect was observed in DE across days. In conclusion, the assessment of the efficiency of low power cycling by linear regression – and conducted within the range of EE observed for low‐intensity movements of everyday life (1.5–4 METs) – extends the capacity for metabolic phenotyping in the inactive population

Dental-derived stem cells and biowaste biomaterials: What's next in bone regenerative medicine applications

The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs), so called dental-derived stem cells (D-dSCs) with self-renewing and multilineage differentiation capabilities. D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Altogether, this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes, and offers information regarding the available scientific data and possible applications

Long-Term Survival and Risk of Institutionalization in Onco-Geriatric Surgical Patients:Long-Term Results of the PREOP Study

OBJECTIVES: To evaluate long-term survival and institutionalization in onco-geriatric surgical patients, and to analyze the association between these outcomes and a preoperative risk score. DESIGN: Prospective cohort study with long-term follow-up. SETTING: International and multicenter locations. PARTICIPANTS: Patients aged 70 years or older undergoing elective surgery for a malignant solid tumor at five centers (n = 229). MEASUREMENTS: We assessed long-term survival and institutionalization using the Preoperative Risk Estimation for Onco-geriatric Patients (PREOP) score, developed to predict the 30-day risk of major complications. The PREOP score collected data about sex, type of surgery, and the American Society for Anesthesiologists classification, as well as the Timed Up & Go test and the Nutritional Risk Screening results. An overall score higher than 8 was considered abnormal. RESULTS: We included 149 women and 80 men (median age = 76 y; interquartile range = 8). Survival at 1, 2, and 5 years postoperatively was 84%, 77%, and 56%, respectively. Moreover, survival at 1 year was worse for patients with a PREOP risk score higher than 8 (70%) compared with 8 or lower (91%). Of those alive at 1 year, 43 (26%) were institutionalized, and by 2 years, almost half of the entire cohort (46%) were institutionalized or had died. A PREOP risk score higher than 8 was associated with increased mortality (hazard ratio = 2.6; 95% confidence interval [CI] = 1.7-4.0), irrespective of stage and age, but not with being institutionalized (odds ratios = 1 y, 1.6 [95% CI =.7-3.8]; 2 y, 2.2 [95% CI =.9-5.5]). CONCLUSION: A high PREOP score is associated with mortality but not with remaining independent. Despite acceptable survival rates, physical function may deteriorate after surgery. It is imperative to discuss treatment goals and expectations preoperatively to determine if they are feasible. Using the PREOP risk score can provide an objective measure on which to base decisions. J Am Geriatr Soc 68:1235–1241, 2020

Dental-derived stem cells and biowaste biomaterials: What’s next in bone regenerative medicine applications

The human teeth and oral cavity harbor various populations of mesenchymal stem cells (MSCs), so called dental-derived stem cells (D-dSCs) with self-renewing and multilineage differentiation capabilities. D-dSCs properties involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Altogether, this viewpoint develops a general picture of current innovative strategies to employ D-dSCs combined with biomaterials and bioactive factors for regenerative medicine purposes, and offers information regarding the available scientific data and possible applications

Quality of Life in Older Adults After Major Cancer Surgery:The GOSAFE International Study

Abstract Background Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL. Methods GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale. Results Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P < .001). Domains showing improvement were pain and anxiety or depression. A Flemish Triage Risk Screening Tool score greater than or equal to 2 (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.13 to 2.21, P = .007), palliative surgery (OR = 2.14, 95% CI = 1.01 to 4.52, P = .046), postoperative complications (OR = 1.95, 95% CI = 1.19 to 3.18, P = .007) correlated with worsening QoL. Conclusions GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations

Correction: "Timed Up & Go":A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? A Multicenter Cohort Study (vol 9, e0086863, 2014)

<p>Correction: "Timed Up & Go": A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? <i>A Multicenter Cohort Study</i></p

The Distribution of Dengue Virus Serotype in Quang Nam Province (Vietnam) during the Outbreak in 2018

Objectives: Quang Nam province in the Centre of Vietnam has faced an outbreak of dengue hemorrhagic fever (DHF) in 2018. Although DHF is a recurrent disease in this area, no epidemiological and microbiological reports on dengue virus serotypes have been conducted mainly due to lack of facilities for such a kind of advanced surveillance. The aim of this study was to detect different dengue virus serotypes in patients’ blood samples. Design and Methods: Suspected cases living in Quang Nam province (Vietnam) and presenting clinical and hematological signs of dengue hemorrhagic fever were included in the study. The screening was performed, and the results were compared by using two methodologies: RT real-time PCR (RT-rPCR) and the Dengue NS1 rapid test. Results: From December 2018 to February 2019, looking both at RT-rPCR [+] and NS1 [+] methodologies, a total of 488 patients were screened and 336 were positive for dengue virus detection (74 children and 262 adults); 273 of these patients (81.3%) underwent viral serotype identification as follows: 12.82% (35/273) D1 serotype, 17.95% (49/273) D2, 0.37% (1/273) D3, 68.50 (187/283) D4, and 0.37% (1/273) D2+D4 serotypes. The RT-rPCR outcomes showed higher sensitivity during the first three days of infection compared to NS1 (92.3% vs. 89.7%). The NS1 increased sensitivity after the first 3 days whilst the RT-rPCR decreased. Conclusions: Advanced surveillance with dengue virus serotypes identification, if performed routinely, may help to predict and prevent further DHF epidemics based on the exposure of the different serotypes during different periods that lead to the intensification of disease severity as a consequence of antibody-dependent enhancement (ADE)

CXCL12 and [N33A]CXCL12 in 5637 and HeLa Cells: Regulating HER1 Phosphorylation via Calmodulin/Calcineurin

In the human neoplastic cell lines 5637 and HeLa, recombinant CXCL12 elicited, as expected, downstream signals via both G-protein-dependent and β-arrestin-dependent pathways responsible for inducing a rapid and a late wave, respectively, of ERK1/2 phosphorylation. In contrast, the structural variant [N33A]CXCL12 triggered no β-arrestin-dependent phosphorylation of ERK1/2, and signaled via G protein-dependent pathways alone. Both CXCL12 and [N33A]CXCL12, however, generated signals that transinhibited HER1 phosphorylation via intracellular pathways. 1) Prestimulation of CXCR4/HER1-positive 5637 or HeLa cells with CXCL12 modified the HB-EGF-dependent activation of HER1 by delaying the peak phosphorylation of tyrosine 1068 or 1173. 2) Prestimulation with the synthetic variant [N33A]CXCL12, while preserving CXCR4-related chemotaxis and CXCR4 internalization, abolished HER1 phosphorylation. 3) In cells knockdown of β-arrestin 2, CXCL12 induced a full inhibition of HER1 like [N33A]CXCL12 in non-silenced cells. 4) HER1 phosphorylation was restored as usual by inhibiting PCK, calmodulin or calcineurin, whereas the inhibition of CaMKII had no discernable effect. We conclude that both recombinant CXCL12 and its structural variant [N33A]CXCL12 may transinhibit HER1 via G-proteins/calmodulin/calcineurin, but [N33A]CXCL12 does not activate β-arrestin-dependent ERK1/2 phosphorylation and retains a stronger inhibitory effect. Therefore, we demonstrated that CXCL12 may influence the magnitude and the persistence of signaling downstream of HER1 in turn involved in the proliferative potential of numerous epithelial cancer. In addition, we recognized that [N33A]CXCL12 activates preferentially G-protein-dependent pathways and is an inhibitor of HER1

A Nutrition and Conditioning Intervention for Natural Bodybuilding Contest Preparation: Case Study.

Bodybuilding competitions are becoming increasingly popular. Competitors are judged on their aesthetic appearance and usually exhibit a high level of muscularity and symmetry and low levels of body fat. Commonly used techniques to improve physique during the preparation phase before competitions include dehydration, periods of prolonged fasting, severe caloric restriction, excessive cardiovascular exercise and inappropriate use of diuretics and anabolic steroids. In contrast, this case study documents a structured nutrition and conditioning intervention followed by a 21 year-old amateur bodybuilding competitor to improve body composition, resting and exercise fat oxidation, and muscular strength that does not involve use of any of the above mentioned methods. Over a 14-week period, the Athlete was provided with a scientifically designed nutrition and conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not neglect any macronutrient groups; (iii) exercise regularly but not excessively and; (iv) incorporate rest days into his conditioning regime. This strategy resulted in a body mass loss of 11.7 kg’s, corresponding to a 6.7 kg reduction in fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there was a near 3-fold increase in the corresponding exercise intensity that elicited the maximal rate of fat oxidation; 21% V̇ O2max to 60% V̇ O2max. Hamstring concentric peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood-state (BRUMS scale) was not negatively influenced by the intervention and all values relating to the Athlete’s mood-state remained below average over the course of study. This intervention shows that a structured and scientifically supported nutrition strategy can be implemented to improve parameters relevant to bodybuilding competition and importantly the health of competitors, therefore questioning the conventional practices of bodybuilding preparation