Swallowing outcomes after transoral robotic surgery and adjuvant treatment in unknown primary.

OBJECTIVES: Robotic transoral mucosectomy of the base of tongue was introduced as a diagnostic procedure in patients treated for head and neck cancer with unknown primary (CUP), increasing the identification rate of the primary tumour. For the treatment of CUP, a considerable percentage of patients require adjuvant (chemo)radiation. The aim of this study was to investigate swallowing outcomes among CUP patients after TORS and adjuvant treatment. SUBJECTS AND METHODS: A systematic review was carried out on studies investigating the impact of TORS and adjuvant treatment on swallowing-related outcomes among CUP patients In addition, a cross-sectional study was carried out on swallowing problems (measured using the SWAL-QOL questionnaire) among CUP patients in routine care who visited the outpatient clinic 1-5 years after TORS and adjuvant treatment. RESULTS: The systematic review (6 studies; n = 98) showed that most patients returned to a full oral diet. The cross-sectional study (n = 12) showed that all patients were able to return to a full oral diet, nevertheless, 50% reported swallowing problems in daily life (SWAL-QOL total score ≥14). CONCLUSION: Although after TORS and adjuvant treatment for CUP a full oral diet can be resumed, patients still experience problems with eating and drinking in daily life.

Circulating T cell status and molecular imaging may predict clinical benefit of neoadjuvant PD-1 blockade in oral cancer.

BACKGROUND: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome. METHODS: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included 18F-BMS-986192 (PD-L1) PET and 18F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology. RESULTS: Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8+ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1. CONCLUSION: Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations.

Skull base surgery for malignant tumors: The 2nd international collaborative study (1995-2015).

BACKGROUND: The current study presents the effort of a global collaborative group to review the management and outcomes of malignant tumors of the skull base worldwide. PATIENTS AND METHODS: A total of 28 institutions contributed data on 3061 patients. Analysis evaluated clinical variables, survival outcomes, and multivariable factors associated with outcomes. RESULTS: The median age was 56 years (IQR 44-67). The open surgical approach was used in 55% (n = 1680) of cases, endoscopic resection was performed in 36% (n = 1087), and the combined approach in 9.6% (n = 294). With a median follow-up of 7.1 years, the 5-year OS DSS and RFS were 65%, 71.7% and 53%, respectively. On multivariable analysis, older age, comorbidities, histology, dural/intracranial involvement, positive margins, advanced stage, and primary site were independent prognostic factors for OS, DSS, and RFS. Adjuvant RT was a protective prognostic factor. CONCLUSION: The progress across various disciplines may have contributed to improved OS and DSS in this study compared to previous reports.

Surgery versus sclerotherapy versus combined therapy in head and neck lymphatic malformations in the pediatric population: systematic review and meta-analysis.

PURPOSE: To systematically review current literature on the treatment of lymphatic malformations (LMs) of the head and neck to guide treatment strategy. METHODS AND MATERIALS: A systematic review and meta-analysis of literature until 16 November 2021 was performed on treatments of LMs in the head and neck. RESULTS: Out of 9044 articles, 54 studies were eligible for inclusion with 26 studies providing detailed participant data. A total number of 1573 patients with a mean age of 21.22 months were analysed. Comparative meta-analysis did not reveal significant differences two proportions of volume reduction (≥ 50% and 100%) between sclerotherapy and surgical treatment. Regression demonstrated that positive predictors for volume reduction were surgery 17 (95% CI 0.26-34; p = 0.047) and treatment of macrocystic lesions 19 (95% CI 5.5-32; p = 0.006). Treatment of mixed lesions also demonstrated a trend towards achieving a greater volume reduction (p = 0.052). A higher de Serres stage of the lesion had a negative effect on the amount of volume reduction - 3.7 (95% CI - 7.0 to - 0.35; p = 0.030). CONCLUSION: This comprehensive meta-analysis demonstrated no significant difference in volume reduction between various treatment modalities at study level. However, individual patient data indicated that surgery and larger cyst types are associated with a significant higher percentage of volume reduction, whereas a higher de Serres stage negatively impacted the amount of volume reduction. These findings can be used for patient counseling and treatment planning based on cyst type and de Serres stage. However volume reduction constitutes just one objective within a more complex treatment spectrum.

In Vitro Model of Prepacked Carbon Dioxide Absorber Use: Development and Testing.

BACKGROUND: Carbon dioxide absorbers allow the use of fresh gas flow below minute ventilation (V˙E). Models are developed and tested in vitro to quantify their performance with variable carbon dioxide load (V˙CO2), fresh gas flow, V˙E, end-tidal carbon dioxide (ETco2) fraction, and the type of workstation used. METHODS: First principles are used to derive a linear relationship between fresh gas flow and fractional canister usage or FCU0.5 (the reciprocal of the time for the inspiratory carbon dioxide fraction to reach 0.5%). This forms the basis for two basic models in which V˙E was measured by spirometry or calculated. These models were extended by multiplying V˙E with an empirical workstation factor. To validate the four models, two hypotheses were tested. To test whether the FCU0.5 intercept varied proportionally with V˙CO2 and was independent of V˙E, FCU was measured for 10 canisters tested with a fixed 0.3 l/min fresh gas flow and a range of V˙CO2 while V˙E was either constant or adjusted to maintain ETco2 fraction. A t test was used to compare the two groups. To confirm whether a change in V˙CO2 accompanied by a change in V˙E to maintain ETco2 fraction would shift the linear fresh gas flow-FCU0.5 relationship in a parallel manner, 19 canisters were tested with different combinations of V˙CO2 and fresh gas flow. These measured FCU values were compared to those predicted by the four models using Varvel's performance criteria. RESULTS: With 0.3 l/min fresh gas flow, FCU0.5 was proportional with V˙CO2 and independent of whether V˙E was adjusted to maintain ETco2 fraction or not (P = 0.962). The hypothesized parallel shift of the fresh gas flow-FCU0.5 relationship was confirmed. Both extended models are good candidate models. CONCLUSIONS: The models predict prepacked canister performance in vitro over the range of V˙E, fresh gas flow, and V˙CO2 likely to be encountered in routine clinical practice. In vivo validation is still needed.

Changes in multidisciplinary team decisions in a high volume head and neck oncological center following those made in its preferred partner.

Objective: Head and neck cancer care is highly complex, and multidisciplinary team meetings (MDTs) are vital for improved outcomes. In the Netherlands, head and neck cancer care is practiced in eight high-volume head and neck oncologic centers (HNOC) and six affiliated hospitals preferred partner (PP) centers. Patients treated in the PP are presented and discussed in the HNOC. To evaluate the importance of these mandatory and decisive steps in decision making, we have assessed the changes in treatment. Materials and methods: Retrospective evaluation of head and neck cancer patients referred between January 2011 and October 2018 for a MDT evaluation to the HNOC was conducted. The differences in MDT recommendation were classified with regards to major and minor changes. Results: Management recommendation(MR) changed after 113 of 515 MDT discussions within the PP (487 patients; 22%), of which 86 cases (16%) were major changes. In 67 cases (59.3%), escalation of management was recommended, while in 43 cases (38.1%) de-escalation was recommended. Conclusion: There was a high rate of change of MRs, when comparing the PP recommendations with the HNOC recommendations. Since patient and tumor characteristics seem unable to predict these changes, we recommend all patients be seen for a clinical presentation, revision of diagnostics, and MDT discussion in a high volume HNOC.

Incomplete patient information exchange and unnecessary repeat diagnostics during oncological referrals in the Netherlands: exploring the role of information exchange.

Data management in transmural care is complex. Without digital innovations like Health Information Exchange (HIE), patient information is often dispersed and inaccessible across health information systems between hospitals. The extent of information loss and consequences remain unclear. We aimed to quantify patient information availability of referred oncological patients and to assess its impact on unnecessary repeat diagnostics by observing all oncological multidisciplinary team meetings (MDTs) in a tertiary hospital. During 84 multidisciplinary team meetings, 165 patients were included. Complete patient information was provided in 17.6% (29/165, CI = 12.3-24.4) of patients. Diagnostic imaging was shared completely in 52.5% (74/141, CI = 43.9-60.9), imaging reports in 77.5% (100/129, CI = 69.2-84.2), laboratory results in 55.2% (91/165, CI = 47.2-62.8), ancillary test reports in 58.0% (29/50, CI = 43.3-71.5), and pathology reports in 60.0% (57/95, CI = 49.4-69.8). A total of 266 tests were performed additionally, with the main motivation not previously performed followed by inconclusive or insufficient quality of previous tests. Diagnostics were repeated unnecessarily in 15.8% (26/165, CI = 10.7-22.4) of patients. In conclusion, patient information was provided incompletely in majority of referrals discussed in oncological multidisciplinary team meetings and led to unnecessary repeat diagnostics in a small number of patients. Additional research is needed to determine the benefit of Health Information Exchange to improve data transfer in oncological care.

Development and validation of a model to calculate anesthetic agent consumption from inspired and end-expired concentrations, minute ventilation, fresh gas flow and dead space ventilation.

Anesthetic agent consumption is often calculated as the product of fresh gas flow (FGF) and vaporizer dial setting (FVAP). Because FVAP of conventional vaporizers is not registered in automated anesthesia records, retrospective agent consumption studies are hampered. The current study examines how FVAP can be retrospectively calculated from the agent's inspired (FIN) and end-expired concentration (FET), FGF, and minute ventilation (MV). Theoretical analysis of agent mass balances in the circle breathing reveals FVAP = [FIN - (dead space fraction * FIN + (1 - dead space fraction) * FET) * (1 - FGF/MV)]/(1-(1 - FGF/MV)). FIN, FET, FGF and MV are routinely monitored, but dead space fraction is unknown. Dead space fraction for sevoflurane, desflurane, and isoflurane was therefore determined empirically from an unpublished data set of 161 patient containing FVAP, FIN, FET, MV and FGF ranging from 0.25 to 8 L/min delivered via an ADU® (GE, Madison, WI, USA). Dead space fraction for each agent was determined empirically by having Excel's solver function calculate the value of dead space fraction that minimized the sum of the squared differences between dialed FVAP and predicted FVAP. With dead space fraction known, the model was then prospectively tested for sevoflurane in O2/air using data collected over the course of two weeks with one FLOW-i (Getinge, Solna, Sweden) and one Zeus workstation (Dräger, Lübeck, Germany). Because both workstations use an electronically controlled vaporizer/injector, the dialed FVAP were available to allow the calculation of median performance error (MDPE) and median absolute performance error (MDAPE). MDPE and MDAP are reported as median and interquartiles. The empirical dead space fraction for isoflurane, sevoflurane, and desflurane were 0.59, 0.49, and 0.66, respectively. For prospective testing, a total of 149.4 h of useful data were collected from 78 patient with the Zeus and Flow-i combined, with FGF ranging from 0.18 to 8 L/min. The model predicted dialed FVAP well, with a MDPE of -1 (-11, 6) % and MDAPE of 8 (4, 17) %. FVAP can be retrospectively calculated from FIN, FET, FGF, and MV plus an agent specific dead space fraction factor with a degree of error that we believe suffices for retrospective sevoflurane consumption analyses. Performance with other agents and N2O awaits further validation.

Arterial to end-tidal CO2 gradients during isocapnic hyperventilation.

Isocapnic hyperventilation (ICHV) is occasionally used to maintain the end-expired CO2 partial pressure (PETCO2) when the inspired CO2 (PICO2) rises. Whether maintaining PETCO2 with ICHV during an increase of the PICO2 also maintains arterial PCO2 (PaCO2) remains poorly documented. 12 ASA PS I-II subjects undergoing a robot-assisted radical prostatectomy (RARP) (n = 11) or cystectomy (n = 1) under general endotracheal anesthesia with sevoflurane in O2/air (40% inspired O2) were enrolled. PICO2 was sequentially increased from 0 to 0.5, 1.0, 1.5 and 2% by adding CO2 to the inspiratory limb of the circle system, while increasing ventilation to a target PETCO2 of 4.7-4.9% by adjusting respiratory rate during controlled mechanical ventilation. Pa-ETCO2 gradients were determined after a 15 min equilibration period at each PICO2 level and compared using ANOVA. Mean (standard deviation) age, height, and weight were 66 (6) years, 171 (6) cm, and 75 (8) kg, respectively. Capnograms were normal and hemodynamic parameters remained stable. PETCO2 could be maintained within 4.7-4.9% in all subjects at all times except in 1 subject with 1.5% PICO2 and 5 subjects with 2.0% PICO2; data from the one subject in whom both 1.5 and 2.0% PICO2 resulted in PETCO2 > 5.1% were excluded from analysis. Pa-ETCO2 gradients did not change when PICO2 increased. The effect of a modest rise of PICO2 up to 1.5% on PETCO2 during RARP can be readily overcome by increasing ventilation without altering the Pa-ETCO2 gradients. At higher PICO2, airway pressures may become a limiting factor, which requires further study.

Practice of oxygen use in anesthesiology - a survey of the European Society of Anaesthesiology and Intensive Care.

BACKGROUND: Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear. METHODS: We conducted an online survey among members of the European Society of Anaesthesiology and Intensive Care (ESAIC). The questionnaire consisted of 46 queries appraising the perioperative period, emergency medicine and in the intensive care, knowledge about current recommendations by the WHO, oxygen toxicity, and devices for supplemental oxygen therapy. RESULTS: Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals with > 500 beds. The majority affirmed that they do not use specific protocols for oxygen administration. WHO recommendations are unknown to 42% of respondents, known but not followed by 14%, and known and followed by 24% of them. Respondents prefer inspiratory oxygen fraction (FiO2) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO2), but shortage of devices still limits monitoring. When monitoring is used, SpO2 ≤ 95% is often targeted. In critical emergency medicine, oxygen is used frequently in patients aged ≥80 years, or presenting with respiratory distress, chronic obstructive pulmonary disease, myocardial infarction, and stroke. In the intensive care unit, oxygen is mostly targeted at 96%, especially in patients with pulmonary diseases. CONCLUSIONS: The current practice of perioperative oxygen therapy among respondents does not follow WHO recommendations or current evidence, and access to postoperative monitoring devices impairs the individualization of oxygen therapy. Further research and additional teaching about use of oxygen are necessary.

A Rare Case of Cemento-Ossifying Fibroma of the Maxilla.

Teaching Point: Cemento-ossifying fibromas are rare, benign tumours that are mostly found in the tooth-bearing areas of the mandible or maxilla and can be seen on cone-beam computed tomography.

The science behind banning desflurane: A narrative review.

Potent inhaled anaesthetics are halogenated hydrocarbons with a large global warming effect. The use of fluorinated hydrocarbons (most are not anaesthetics) are being restricted but volatile anaesthetics have been exempted from legislation, until now: the EU has formulated a proposal to ban or at least severely restrict the use of desflurane starting January 2026. This narrative review addresses the implications of a politics-driven decision - without prior consultation with major stakeholders, such as the European Society of Anaesthesiology and Intensive Care (ESAIC) - on daily anaesthesia practice and reviews the potential scientific arguments that would support stopping the routine use of desflurane in anaesthetic practice. Of note, banning or severely restricting the use of one anaesthetic agent should not distract the user from sensible interventions like reducing fresh gas flows and developing technology to capture and recycle or destroy the wasted potent inhaled anaesthetics that we will continue to use. We call to join efforts to minimise our professional environmental footprint.

Hyperdense Basal Ganglia on Brain CT in Non-Ketotic Hyperglycemia Associated with Hemichorea.

Teaching Point: Unilateral choreiform movements combined with contralateral hyperdense lentiform and/or caudate nucleus on computed tomography is suggestive for non-ketotic hyperglycemia, warranting further metabolic workup.

Prospective validation of gas man simulations of sevoflurane in O2/air over a wide fresh gas flow range.

The use of inhaled anesthetics has come under increased scrutiny because of their environmental effects. This has led to a shift where sevoflurane in O2/air has become the predominant gas mixture to maintain anesthesia. To further reduce environmental impact, lower fresh gas flows (FGF) should be used. An accurate model of sevoflurane consumption allows us to assess and quantify the impact of the effects of lowering FGFs. This study therefore tested the accuracy of the Gas Man® model by determining its ability to predict end-expired sevoflurane concentrations (FETsevo) in patients using a protocol spanning a wide range of FGF and vaporizer settings. After IRB approval, 28 ASA I-II patients undergoing a gynecologic or urologic procedure under general endotracheal anesthesia were enrolled. Anesthesia was maintained with sevoflurane in O2/air, delivered via a Zeus or FLOW-i workstation (14 patients each). Every fifteen min, FGF was changed to randomly selected values ranging from 0.2 to 6 L/min while the sevoflurane vaporizer setting was left at the discretion of the anesthesiologist. The FETsevo was collected every min for 1 h. For each patient, a Gas Man® simulation was run using patient weight and the same FGF, vaporizer and minute ventilation settings used during the procedure. For cardiac output, the Gas Man default setting was used (= Brody formula). Gas Man®'s performance was assessed by comparing measured with Gas Man® predicted FETsevo using linear regression and Varvel's criteria [median performance error (MDPE), median absolute performance error (MDAPE), and divergence]. Additional analysis included separating performance for the wash-in (0-15 min) and maintenance phase (15-60 min). For the FLOW-i, MDPE, MDAPE and divergence were 1% [- 6, 8], 7% [3, 15] and - 0.96%/h [- 1.14, - 0.88], respectively. During the first 15 min, MDPE and MDAPE were 18% [1, 51] and 21% [8, 51], respectively, and during the last 45 min 0% [- 7, 5] and 6% [2, 10], respectively. For the Zeus, MDPE, MDAPE and divergence were 0% [- 5, 8], 6% [3, 12] and - 0.57%/h [- 0.85, - 0.16], respectively. During the first 15 min, MDPE and MDAPE were 7% [- 6, 28] and 13% [6, 32], respectively, and during the last 45 min - 1% [- 5, 5] and 5% [2, 9], respectively. In conclusion, Gas Man® predicts FETsevo in O2/air in adults over a wide range of FGF and vaporizer settings using different workstations with both MDPE and MDAPE < 10% during the first hour of anesthesia, with better relative performance for simulating maintenance than wash-in. In the authors' opinion, this degree of performance suffices for Gas Man® to be used to quantify the environmental impact of FGF reduction in real life practice of the wash-in and maintenance period combined.

Memsorb™, a novel CO2 removal device part II: in vivo performance with the Zeus IE®.

Memsorb™ (DMF Medical, Halifax, Canada) is a novel device based upon membrane oxygenator technology designed to eliminate CO2 from exhaled gas when using a circle anesthesia circuit. Exhaled gases pass through semipermeable hollow fibers and sweep gas flowing through these fibers creates a diffusion gradient for CO2 removal. In vivo Memsorb™ performance was tested during target-controlled closed-circuit anesthesia (TCCCA) with desflurane in O2/air using a Zeus IE® anesthesia workstation (Dräger, Lübeck, Germany). Clinical care protocols for using this novel device were guided by in vitro performance results from a prior study (submitted simultaneously). After IRB approval, written informed consent was obtained from 10 ASA PS I-III patients undergoing robot-assisted radical prostatectomy. TCCCA targets were 39% inspired O2 concentration (FIO2) and 5.0% end-expired desflurane concentration (FETdes). Minute ventilation (MV) was adjusted to maintain 4.5-6.0% FETCO2. The O2/air (40% O2) sweep flow into the Memsorb™ was manually adjusted in an attempt to keep inspired CO2 concentration (FICO2) ≤ 0.8%. The following data were collected: FIO2, FETdes, FICO2, FETCO2, MV, fresh gas flow (FGF, O2 and air), sweep flow, and cumulative desflurane usage (Vdes). Vdes of the Zeus IE®-Memsorb™ combination was compared with historical Vdes observed in a previous study when soda lime (DrägerSorb 800 +) was used. Results are reported as median and inter-quartiles. A combination of manually adjusting sweep flow (26 [21,27] L/min) and MV sufficed to maintain FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, except in one patient in whom the target Zeus IE® FGF had to be increased to 0.7 L/min for 6 min. FIO2 and FETdes were maintained close to their targets. Zeus IE® FGF after 5 min was 0 [0,0] mL/min. Average Vdes after 50 min was higher with Memsorb™ (20.3 mL) compared to historical soda lime canister data (12.3 mL). During target-controlled closed-circuit anesthesia in patients undergoing robot-assisted radical prostatectomy, the Memsorb™ maintained FICO2 ≤ 0.8% and FETCO2 ≤ 6.0%, and FIO2 remained close to target. Modest amounts of desflurane were lost with the use of the Memsorb™. The need for adjustments of sweep flow, minute ventilation, and occasionally Zeus IE® FGF indicates that the Memsorb™ system should preferentially be integrated into an automated closed-loop system.

Memsorb™, a novel CO2 removal device part I: in vitro performance with the Zeus IE®.

Soda lime-based CO2 absorbents are safe, but not ideal for reasons of ecology, economy, and dust formation. The Memsorb™ is a novel CO2 removal device that uses cardiopulmonary bypass oxygenator technology instead: a sweep gas passes through semipermeable hollow fibers, adding or removing gas from the circle breathing system. We studied the in vitro performance of a prototype Memsorb™ used with a Zeus IE® anesthesia machine when administering sevoflurane and desflurane in O2/air mixtures. The Zeus IE® equipped with Memsorb™ ventilated a 2L breathing bag with a CO2 inflow port in its tip. CO2 kinetics were studied by using different combinations of CO2 inflow (VCO2), Memsorb™ sweep gas flow, and Zeus IE® fresh gas flow (FGF) and ventilator settings. More specifically, it was determined under what circumstances the inspired CO2 concentration (FICO2) could be kept < 0.5%. O2 kinetics were studied by measuring the inspired O2 concentration (FIO2) resulting from different combinations of Memsorb™ sweep gas flow and O2 concentrations, and Zeus IE® FGFs and O2 concentrations. Memsorb™'s sevoflurane and desflurane waste was determined by measuring their injection rates during target-controlled closed-circuit anesthesia (TCCCA), and were compared to historical controls when using a soda lime absorbent (Draegersorb 800+) under identical conditions. With 160 mL/min VCO2 and 5 L/min minute ventilation (MV), lowering the sweep gas flow at any fixed Zeus IE® FGF increased FICO2 in a non-linear manner. Sweep gas flow adjustments kept FICO2 < 0.5% over the entire Zeus IE® FGF range tested with VCO2 up to 280 mL/min; tidal volume and respiratory rate affected the required sweep gas flow. At 10 L/min MV and low FGF (< 1.5 L/min), even a maximum sweep flow of 43 L/min was unable to keep FICO2 ≤ 0.5%. When the O2 concentration in the Zeus IE® FGF and the Memsorb™ sweep gas flow differed, FIO2 drifted towards the sweep gas O2 concentration, and more so as FGF was lowered; this effect was absent once FGF > minute ventilation. During sevoflurane and desflurane TCCCA, the Zeus IE® FGF remained zero while agent usage per % end-expired agent increased with increasing end-expired target agent concentrations and with a higher target FIO2. Agent waste during target-controlled delivery was higher with Memsorb™ than with the soda lime product, with the difference remaining almost constant over the FGF range studied. With a 5 L/min MV, Memsorb™ successfully removes CO2 with inflow rates up to 240 mL/min if an FICO2 of 0.5% is accepted, but at 10 L/min MV and low FGF (< 1.5 L/min), even a maximum sweep flow of 43 L/min was unable to keep FICO2 ≤ 0.5%. To avoid FIO2 deviating substantially from the O2 concentration in the fresh gas, the O2 concentration in the fresh gas and sweep gas should match. Compared to the use of Ca(OH)2 based CO2 absorbent, inhaled agent waste is increased. The device is most likely to find its use integrated in closed loop systems.

H4K20me3 marks distal intergenic and repetitive regions in human mature spermatozoa.

Sperm histones represent an essential part of the paternally transmitted epigenome, but uncertainty exists about the role of those remaining in non-coding and repetitive DNA. We therefore analyzed the genome-wide distribution of the heterochromatic marker H4K20me3 in human sperm and somatic (K562) cells. To specify the function of sperm histones, we compared all H4K20me3-containing and -free loci in the sperm genome. Sperm and somatic cells possessed a very similar H4K20me3 distribution: H4K20me3 peaks occurred mostly in distal intergenic regions and repetitive gene clusters (in particular genes encoding odorant-binding factors and zinc-finger antiviral proteins). In both cell types, H4K20me3 peaks were enriched in LINEs, ERVs, satellite DNA and low complexity repeats. In contrast, H4K20me3-free nucleosomes occurred more frequently in genic regions (in particular promoters, exons, 5'-UTR and 3'-UTR) and were enriched in genes encoding developmental factors (in particular transcription activators and repressors). H4K20me3-free nucleosomes were also detected in substantial quantities in distal intergenic regions and were enriched in SINEs. Thus, evidence suggests that paternally transmitted histones may have a dual purpose: maintenance and regulation of heterochromatin and guidance towards transcription of euchromatin.