Current methods of forcing end‐tidal P_CO2 (P_ETCO2) and P_O2 (P_ETO2) rely on breath‐by‐breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo‐control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath‐by‐breath basis. In this paper, we introduce a low gas flow method to prospectively target and control P_ETCO2 and P_ETO2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change P_ETCO2 from control (40 mmHg for P_ETCO2 and 100 mmHg for P_ETO2) to two target P_ETCO2 values (45 and 50 mmHg) at iso‐oxia (100 mmHg), P_ETO2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and P_ETCO2 with P_ETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, P_ETCO2 and P_ETO2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for P_ETCO2 was ± 1 mmHg, and for P_ETO2 was ± 4 mmHg. P_ETCO2 varied by ± 1 mmHg and P_ETO2 by ± 5.6 mmHg (s.d.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min⁻¹). We conclude that targeted end‐tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed‐forward, low gas flow system.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time ( P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years ( P = .015). Dry mouth scores were higher in RT patients over time ( P = .041). CONCLUSION: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355 ).

The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques across a variety of otolaryngological sub-specialties suggests an emerging role for rapid prototyping technology in surgical education, procedure simulation, and clinical practice.

Purpose: To assess the effect of changes in end‐tidal partial pressure of O₂ (PETO₂) on cerebrovascular reactivity (CVR) estimated from changes in blood oxygen level–dependent (BOLD) signal during cyclic changes in end‐tidal partial pressure of CO₂ (PETCO₂).Materials and Methods: BOLD response to fixed cyclic step changes in PETCO₂ (range = 30.4–48.8 mmHg) and PETO₂ (range = 100.6–444.0 mmHg) was studied in four healthy volunteers.Results: The BOLD reactivity to PETCO₂ and PETO₂ were 0.283 (0.188–0.379) (median, range) and 0.004 (0.003–0.006)%/mmHg, respectively, in the whole brain; 0.438 (0.382–0.614) vs. 0.006 (0.004–0.009)%/mmHg, respectively, in the gray matter; and 0.075 (0.065–0.093) vs. 0.002 (0.001–0.002)%/mmHg, respectively, in the white matter.Conclusion: The BOLD reactivity to PETO₂ was much smaller than that to PETCO₂. However, BOLD reactivity can be significantly distorted by CO₂‐induced changes in PETO₂. We conclude that PETO₂ should be carefully controlled during studies that use BOLD reactivity as an indicator of CVR. J. Magn. Reson. Imaging 2007.

The study of the biology of evolution has been confined to laboratories and model organisms. However, controlled laboratory conditions are unlikely to model variations in environments that influence selection in wild populations. Thus, the study of “fitness” for survival and the genetics that influence this are best carried out in the field and in matching environments. Therefore, we studied highland populations in their native environments, to learn how they cope with ambient hypoxia. The Andeans, African highlanders and Himalayans have adapted differently to their hostile environment. Chronic mountain sickness (CMS), a loss of adaptation to altitude, is common in the Andes, occasionally found in the Himalayas; and absent from the East African altitude plateau. We compared molecular signatures (distinct patterns of gene expression) of hypoxia-related genes, in white blood cells (WBC) from Andeans with (n = 10), without CMS (n = 10) and sea-level controls from Lima (n = 20) with those obtained from CMS (n = 8) and controls (n = 5) Ladakhi subjects from the Tibetan altitude plateau. We further analyzed the expression of a subset of these genes in Ethiopian highlanders (n = 8). In all subjects, we performed the studies at their native altitude and after they were rendered normoxic. We identified a gene that predicted CMS in Andeans and Himalayans (PDP2). After achieving normoxia, WBC gene expression still distinguished Andean and Himalayan CMS subjects. Remarkably, analysis of the small subset of genes (n = 8) studied in all 3 highland populations showed normoxia induced gene expression changes in Andeans, but not in Ethiopians nor Himalayan controls. This is consistent with physiologic studies in which Ethiopians and Himalayans show a lack of responsiveness to hypoxia of the cerebral circulation and of the hypoxic ventilatory drive, and with the absence of CMS on the East African altitude plateau.