The partial pressure of end tidal carbon dioxide (PETCO 2), ventilatory sensitivity to CO 2, and cerebral perfusion are augmented during thermoneutral head out water immersion (HOWI). We tested the hypotheses that HOWI and acute hypercapnia augments minute ventilation, ventilatory sensitivity to CO 2, cerebral perfusion, and cerebrovascular reactivity to CO 2. Twelve subjects (age: 24 ± 3 years, BMI: 25.3 ± 2.9 kg/m2, 6 women) participated in two experimental visits: a HOWI visit (HOWI) and a matched hypercapnia visit (Dry + CO 2). A rebreathing test was conducted at baseline, 10, 30, 60 min, and post HOWI and Dry + CO 2. PETCO 2, minute ventilation, expired gases, blood pressure, heart rate, and middle cerebral artery blood velocity were recorded continuously. PETCO 2 increased throughout HOWI (baseline: 42 ± 2 mmHg; maximum at 10 min: 44 ± 2 mmHg, P ≤ 0.013) and Dry + CO 2 (baseline: 42 ± 2 mmHg; maximum at 10 min: 44 ± 2 mmHg, P ≤ 0.013) and was matched between conditions (condition main effect: P = 0.494). Minute ventilation was lower during HOWI versus Dry + CO 2 (maximum difference at 60 min: 13.2 ± 1.9 vs. 16.2 ± 2.7 L/min, P < 0.001). Ventilatory sensitivity to CO 2 and middle cerebral artery blood velocity were greater during HOWI versus Dry + CO 2 (maximum difference at 10 min: 2.60 ± 1.09 vs. 2.20 ± 1.05 L/min/mmHg, P < 0.001, and 63 ± 18 vs. 53 ± 14 cm/sec, P < 0.001 respectively). Cerebrovascular reactivity to CO 2 decreased throughout HOWI and Dry + CO 2 and was not different between conditions (condition main effect: P = 0.777). These data indicate that acute hypercapnia, matched to what occurs during HOWI, augments minute ventilation but not ventilatory sensitivity to CO 2 or middle cerebral artery blood velocity despite an attenuated cerebrovascular reactivity to CO 2.
Glioblastoma (GBM) is one of the most malignant primary intracranial neoplasms. This review aims to summarize the treatment of elderly patients with newly diagnosed GBM, with a focus on the radiation therapy (RT) approach. The available literature was reviewed, and we describe the most significant results relating to the post-operative approach of elderly GBM patients. Age limitations in randomized phase III studies have restricted the inclusion of elderly patients, and consequently, limited the generalizability of their results to this patient subset. Chronological age should not prohibit the best treatment, but instead, treatment decisions should consider patient functional status. RT showed efficacy and safety in the elderly population, without compromising quality of life. Hypofractionated RT is not inferior to standard RT. Reduction of overall RT schedule length mitigates the difficulties faced by elderly patients, improving treatment adherence. The addition of both concomitant and adjuvant temozolomide to standard RT is superior to either modality alone and should be the treatment of choice in the subset of patients with good/very good prognosis. It is reasonable to offer hypofractionated RT or temozolomide alone for poor prognosis, and best supportive care (BSC) for very poor prognosis elderly GBM patients. Although combined modality treatment is well established for the management of the good prognosis population, different RT schemes require further investigation with randomized controlled trials to determine the best regimen. A robust analysis of the molecular signatures of GBM in elderly patients might reveal opportunities for clinical protocol modifications to customize management in this group of patients.
No abstract
Carbon dioxide (CO2) retention occurs during head out water immersion (HOWI) despite an augmented central chemosensitivity. To this end, it is unclear if an augmented central chemosensitivity during HOWI is due to CO2 retention alone (i.e., mild hypercapnia) or the combined effects of HOWI (i.e., CO2 retention, central hypervolemia, increased work of breathing, etc.).PurposeWe tested the hypothesis that central chemosensitivity is augmented during dry conditions while breathing hypercapnic gas to match the CO2 retention that occurs during HOWI.MethodsTwelve healthy subjects (age: 24±3 y, BMI: 25±3‐‐ kg/m2, 6 women) completed two experimental visits: a thermoneutral HOWI visit (HOWI) and a dry mild hypercapnia visit (Control+CO2). We measured ventilation (pneumotachometer) and expired CO2 tension (PETCO2; capnography), as an index of CO2 retention, throughout both visits. HOWI consisted of 60 min of thermoneutral (35.0±0.1°C) water immersion to the neck. During Control+CO2, small amounts of CO2 were added to the inspirate to match PETCO2 values that were obtained during HOWI. During both visits, central chemosensitivity was evaluated at baseline, 10 min, 30 min, and 60 min via a rebreathing test where subjects rebreathed 7% CO2 and 93% O2 from a 10 L bag for 3.5 min. Central chemosensitivity was calculated as the slope of the linear regression line of minute ventilation vs. PETCO2 every 30 s throughout the test. Data were analyzed and reported as a change from baseline (mean±SD).ResultsThere were no statistical differences in PETCO2 (p=0.33), minute ventilation (p=0.99), or central chemosensitivity (p=0.59) between HOWI and Control+CO2 at baseline. PETCO2 increased from baseline during HOWI and Control+CO2 at 10 min (HOWI: 2±1 mmHg, p<0.01; Control+CO‐2: 2±2 mmHg, p<0.01), 30 min (HOWI: 1±2 mmHg, p<0.01; Control+CO‐2: 1±2 mmHg, p<0.01), and 60 min (HOWI: 2±2 mmHg, p<0.01; Control+CO2: 2±2 mmHg, p<0.01). The change in PETCO2 was not different between conditions at any time point (p≥0.52). Minute ventilation did not change from baseline during HOWI at any time point (p≥0.66), while it increased from baseline during Control+CO2 at 10 min (2.3±1.7 L/min, p<0.01), 30 min (2.0±2.2 L/min, p<0.01), and 60 min (1.6±1.6 L/min, p<0.01). Minute ventilation was greater during Control+CO2 vs. HOWI at 10 min (p<0.01), 30 min (p<0.01), and 60 min (p<0.01). During HOWI, central chemosensitivity increased from baseline at 10 min (0.32±0.34 L/min/mmHg, p=0.03), 30 min (0.35±0.38 L/min/mmHg, p=0.03), and 60 min (0.36±0.43 L/min/mmHg, p=0.03), while central chemosensitivity did not change during Control+CO2 at 10 min (−0.14±0.40 L/min/mmHg, p=0.74), 30 min (0.03±0.27 L/min/mmHg, p=0.99), and 60 min (0.01±0.47 L/min/mmHg, p=0.99). Central chemosensitivity was greater during HOWI vs. Control+CO2 at 10 min (p<0.01), 30 min (p=0.05), and 60 min (p=0.03).ConclusionThese data indicate that central chemosensitivity is not augmented during dry conditions while breathing hypercapnic gas to match the CO2 retention that occurs during HOWI. Thus, it appears that an augmented central chemosensitivity during HOWI is a function of the combined effects of HOWI and not solely CO2 retention.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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