Endovascular Repair of Penetrating Thoracic Aortic Ulcers Using Tubular Stent Grafts Versus Stent Grafts With a Proximal Scallop.

PURPOSE: In penetrating aortic ulcers (PAUs), limited data support tubular thoracic endovascular aortic repair (TEVAR) as a viable treatment option. For treatment of more proximal PAUs, hybrid approaches and-more recently-scalloped TEVAR (scTEVAR) have been advocated. Outcomes of scTEVAR specifically for PAUs have not yet been reported. This study reports long-term outcomes for tubular and scTEVAR in PAUs and compares the safety profile in both cohorts regarding the significantly more proximal landing zone (LZ) for scTEVAR. MATERIALS AND METHODS: This single-center retrospective cohort study includes all nonacute patients treated for complicated PAU with scTEVAR and tubular TEVAR. Patient and PAU characteristics as well as procedural success, complication and reintervention rates, and all-cause and aortic mortality were analyzed. RESULTS: Of 212 TEVAR procedures reviewed, 21 patients with tubular TEVAR and 19 patients with scTEVAR were included. Patient and PAU characteristics were similar, and LZ was significantly more proximal in the scTEVAR cohort (p=0.0001), with similar number and types of supra-aortic revascularization procedures. Clinical success was reached in all 40 patients (100%), and reintervention rate was 2/21 (9.5%) and 1/19 (5.3%), respectively. Over the mean follow-up of 63 (TEVAR) and 53 (scTEVAR) months, clinical success was stable in all patients with one (abdominal) aortic-related mortality in the scTEVAR cohort. CONCLUSION: Treatment of complicated PAUs with TEVAR as well as scTEVAR provides excellent and similar clinical success, stability of clinical success, and aortic survival with acceptable complication and reintervention rates. Scalloped TEVAR safely lengthens the proximal sealing zone to address more proximal pathologies. CLINICAL IMPACT: Treatment of asymptomatic complicated penetrating aortic ulcers (PAUs) with thoracic endovascular aortic repair (TEVAR) provides excellent clinical success and acceptable complication and reintervention rates. More patients become amenable to endovascular treatment by including scalloped TEVAR (scTEVAR) as a means to safely lengthen the proximal sealing zone to address more proximal pathologies.

Systematic literature review and meta-analysis of Clostridium septicum aortitis.

BACKGROUND: Clostridium septicum bacteremia is often associated with occult malignancies (approximately 80%), especially of the right colon. Furthermore, inflammation of the aortic wall can rapidly lead to aneurysm induction through bacterial seeding into atheromatous lesions with consecutive life-threatening rupture. We summarize all published data on this rare and lethal disease to evaluate therapeutic approaches and give valid treatment recommendations because there are no guidelines. METHODS: A systematic review of the literature was conducted screening EMBASE and MEDLINE databases following the PRISMA guidelines with search period from first description to August 25, 2021. RESULTS: There were 72 cases of C septicum aortitis reported in 64 publications. Endovascular aortic repair (EVAR) was performed in a minority of patients (n = 6) unfit for surgery but lacked long-term survivors. Antibiotic treatment was beneficial in a bridge to surgery concept, but up to now harbored a 6-month mortality rate of 100% (median overall survival, 0.5 months) when no additional aortic repair was performed. Open aortic repair was the only potential curative approach but was accompanied with a 90-day-mortality of 26.7% (4/15). CONCLUSIONS: Open aortic repair combined with perioperative antibiotic treatment should be offered to all patients as the only potentially curative approach. If applicable, resection of a coexisting colonic tumor should be performed after successful aortic repair. Alternatively, long-term antibiotic treatment can be offered to patients unfit for surgery in a palliative setting. Endovascular aortic repair has been performed on a minority of patients with a high risk for stent graft infection and should remain a salvage strategy when therapeutic pressure demands acute intervention in patients unfit for surgery.

Response prediction by mutation- or methylation-specific detection of ctDNA dynamics in pretreated metastatic colorectal cancer.

Background: Serial analysis of circulating tumor DNA (ctDNA) levels is a promising tool for both relapse prediction in the curative setting, as well as predicting clinical benefit from systemic treatment in metastasic colorectal cancer (mCRC). Most data in this context are derived from treatment naive patients. Objective: To predict progressive disease (PD) as early as possible through monitoring of changes in ctDNA levels during systemic treatment in pretreated patients with mCRC. Design: A prospective, single-center, observational study. Methods: Patients treated beyond first-line were prospectively included between February 2020 and September 2021. Blood for ctDNA detection was taken before every treatment cycle from start of treatment until first restaging by CT-scan. ctDNA was detected by mutation- (mut-ctDNA) and methylation-specific ddPCR. Receiver Operating Characteristic (ROC)-analysis was used to describe sensitivity and specificity for prediction of PD at restaging for all time points. Results: A total of 42 patients were included who all carried a mutation in tumor tissue. Detection rate of mut-ctDNA was 88.1% and 74.4% for meth-ctDNA. Absolute ctDNA levels before treatment were prognostic in terms of overall survival. Levels of ctDNA were significantly higher in patients with PD at restaging. Median time from start of treatment to restaging was 93 days (95% CI 88.8-96). After a median of 19 days of treatment (95% CI 16.1-20.2), a decline of either mutation- or methylation-specific ctDNA levels of ⩽58% predicted PD at restaging with a sensitivity/specificity of 92.9/85.7% and 85.7/100%, respectively. Median time to restaging was 66 days (95% CI 56.8-75.2). There was no significant increase of sensitivity/specificity at later time points of ctDNA measurements. Conclusion: Monitoring early changes of ctDNA levels either by mut- or meth-ctDNA allows for early prediction of PD in pretreated patients with mCRC. This has the potential to complement RECIST-based treatment assessment with the aim to switch potentially insufficient treatments as early as possible, which is of particular interest in higher treatment lines.

Human blood and plasma partition coefficients for C4-C8 n-alkanes, isoalkanes, and 1-alkenes.

Human blood:air and plasma:air partition coefficients for C(4)-C(8) n-alkanes, isoalkanes, and 1-alkenes were determined using multiple headspace extraction coupled with solid phase microextraction and gas chromatography. Mean blood:air partition coefficients expressed in the form of dimensionless blood-to-air concentration ratio (g/mL(b)/g/mL(a)) were 0.183, 0.416, 1.08, 2.71, and 5.77 for C(4)-C(8) n-alkanes; 0.079, 0.184, 0.473, 1.3, and 3.18 for C(4)-C(8) isoalkanes; and 0.304, 0.589, 1.32, 3.5, and 7.01 for C(4)-C(8) 1-alkenes, respectively (n = 8). The reported partition coefficient values increased exponentially with boiling points, molecular weights, and the carbon atoms in the particle. The solubility of 1-alkenes in blood was higher than in plasma, whereas the blood:air and plasma:air partition coefficients of n-alkanes and isoalkanes did not differ significantly. Consequently, additional interactions of 1-alkenes with whole blood seem to occur. The presented findings are expected to be particularly useful for assessing the uptake, distribution, and elimination of hydrocarbons in human organism.

Prospects of conservative treatment for Clostridium septicum-associated aortitis.

Clostridium septicum bacteremia is a rare (72 cases reported) aneurysm-inducing disease that has resulted in a 6-month mortality of 100% when treated conservatively. We report the case of a patient who was completely symptom free at 6 months of follow-up but who ultimately died at 8.9 months after aortic rupture. In compliance with the patient's choice, a long-time antibiotic regimen was applied, instead of the surgical approach recommended by our surgical department. The use of an antibiotic regimen represents an option for patients unfit for surgery or as a bridge to surgery for damage control; however, aortic repair represents the only curative approach. Definitive antibiotic treatment is limited to a palliative approach for patients with C. septicum aortitis and has been accompanied by 100% 1-year mortality (90-day mortality, 84.2%).

Use of a Steerable Sheath for Completely Femoral Access in Branched Endovascular Aortic Repair Compared to Upper Extremity Access.

PURPOSE: To compare bridging stent graft (BSG) implantation in downward oriented branches in branched endovascular aortic repair (bEVAR), using a commercially available steerable sheath from an exclusively femoral access (TFA) with traditional upper extremity access (UEA). METHODS: In a retrospective cohort study, 7 patients with 19 branches in the TFA cohort received BSG insertion using the Medtronic Heli FX steerable sheath from a femoral access, and 10 patients with 32 branches in the UEA cohort from a brachial approach. Technical success, total intervention time, fluoroscopy time, branch cannulation time, and complication rate were recorded. RESULTS: Technical success was 19/19 branches in the TFA and 31/32 in the UEA cohort. The mean branch cannulation time was considerably shorter in the TFA group (17 vs. 29 min, p = 0.003), and total intervention time tended to be shorter (169 vs. 217 min, p = 0.176). CONCLUSION: Using a commercially available steerable sheath allowed successful cannulation of all branches in this cohort and was associated with significantly shorter branch cannulation times. Potentially, this technique can lower the stroke and brachial puncture site complication risk as well as reduce total intervention time and radiation dose. LEVEL OF EVIDENCE: 2b, retrospective cohort study.

Data of 'Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage'.

This data article subsumes the data acquiration process, analysis and results of 'Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage' published in European Journal of Surgical Oncology (Eur J Surg Oncol. 2021 Dec 1:S0748-7983(21)00947-1. doi:10.1016/j.ejso.2021.11.138. PMID: 34876329) (Kirchweger et al., 2021). 28.5 mL of blood was obtained from 60 patients with localized pancreatic cancer directly prior to curative intended surgery as well as from 47 patients with metastasized pancreatic cancer (PDAC) directly prior to palliative intended systemic treatment initiation. Cell-free DNA preparation was done on the Chemagic 360 (Perkin Elmer, Waltham, Massachusetts, USA) using the kits CMG-1304 and CMG-844 from the same provider and quantified using the Quantus fluorometer (Promega, Madison, Wisconsin, USA). Screening for most common KRAS alterations (KRAS G12/G13 screening kit and additionally for KRAS Q61 if screening was negative) was performed utilizing the QX200™ Droplet Digital™ PCR System from Bio-Rad (Bio-Rad Laboratories, Hercules, CA, USA). Volumetric analysis was performed on contrast enhanced dual-energy CT scans in the arterial and portal venous phase prior to treatment initiation using Syngo.via (Siemens Healthcare, Forchheim, Germany) on MM Oncology Workflow adhering to RECIST 1.1 criteria (Eisenhauer et al., 2009). CtDNA predicts outcome in localized and disseminated disease. Moreover, it correlates with distant metastasis volume and positive lymph nodes but not primary tumor volume and therefore could indicate subclinical synchronous distant metastases in localized PDAC undetectable by current gold standard (computed tomography).

Prediction of response to systemic treatment by kinetics of circulating tumor DNA in metastatic pancreatic cancer.

Introduction: Pretherapeutic detectable circulating tumor DNA (ctDNA) represents a promising prognostic biomarker for predicting relapse and overall survival in patients with metastatic pancreatic cancer. However, the prognostic value of ctDNA dynamics during treatment has not been studied thus far. We aimed to investigate the correlation between the change of ctDNA levels and response to treatment in patients treated by systemic therapy. Material and methods: CtDNA detection using liquid biopsy (droplet digital PCR (ddPCR) utilizing KRAS G12/13 and, if negative, Q61 commercial test kits) was prospectively performed on patients with stage IV pancreatic cancer i) prior to initiation of systemic chemotherapy and ii) serially every 2 weeks until restaging. Detection rates, levels of ctDNA, and the course of the relative ctDNA change (ctDNA kinetics) were correlated to treatment response and clinical outcome. Results: The detection rate at baseline was 64.3% (45/70), and complete serial measurement records were available for 32 ctDNA-positive patients. Reduction of ctDNA levels below 57.9% of its baseline value at week 2 after treatment initiation was significantly predictive of response to treatment (area under the curve (AUC) = 0.918, sensitivity 91.67%, and specificity 100%) and was associated with prolonged overall survival (OS) (5.7 vs. 11.4 months, p = 0.006) and progression-free survival (PFS) (2.5 vs. 7.7 months, p < 0.000) regardless of treatment line. Pretherapeutic ctDNA detection was independently associated with worse OS in patients receiving a first-line regimen (7 vs. 11.3 months, p = 0.046) and regardless of treatment line (11.4 vs. 15.9 months, p = 0.045) as well as worse PFS (3.4 vs. 10.8 months, p = 0.018). Conclusion: The change in magnitude of ctDNA during systemic treatment allows the prediction of treatment response and is associated with both OS and PFS. This finding adds significant clinical potential to the already established prognostic value of ctDNA positivity in metastatic pancreatic cancer.

Circulating tumor DNA correlates with tumor burden and predicts outcome in pancreatic cancer irrespective of tumor stage.

INTRODUCTION: Circulating tumor DNA (ctDNA) represents a promising tool for diagnosis, prognosis and treatment monitoring of several malignancies. Its association with tumor burden in pancreatic ductal cancer (PDAC), especially in localized disease, is not fully explored yet. We aimed to investigate the association of pretherapeutic ctDNA levels in localized and metastatic PDAC with tumor volume and clinical outcomes. MATERIAL AND METHODS: Liquid biopsy for ctDNA detection was prospectively obtained from patients with localized or disseminated PDAC prior to either resection or systemic treatment. Detection rates and levels of ctDNA (digital droplet PCR) were correlated to tumor volume, relapse rate and survival. RESULTS: 60 patients with localized and 47 patients with metastatic PDAC were included. ctDNA was detected in 10% of localized and 57.4% of metastasized PDAC samples. In localized disease, ctDNA detection significantly correlated with the numbers of involved locoregional lymph nodes (p = 0.030). Primary tumor volume did not correlate with ctDNA levels in neither localized (p = 0.573) nor metastasized disease (p = 0.878). In disseminated disease, ctDNA levels correlated with total tumor volume (p = 0.026) and especially with liver metastases volume (p = 0.004), but not with other metastases. Detection of pretherapeutic ctDNA was associated with shorter DFS in localized (3.3 vs. 18.1 months, p = 0.000), whereas ctDNA levels were associated with worse survival in metastatic PDAC (5.7 vs. 7.8 months, p = 0.036). CONCLUSION: ctDNA positivity indicates major nodal involvement or even presence of undetected distant metastases associated with early recurrence in localized PDAC. Moreover, it predicts worse clinical outcome in both localized and metastatic disease.

Branched versus fenestrated thoracic endovascular aortic repair in the aortic arch: A multicenter comparison.

OBJECTIVE: For thoracic endovascular aortic repair of the arch, branched and fenestrated endografts are available with different limitations regarding anatomy and extent of the pathology. Comparisons are lacking in the literature. The aim of this study was to compare the results of 2 currently commercially available devices for branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair. METHODS: In a retrospective, multicenter cohort study, a consecutive patient series treated with branched thoracic endovascular aortic repair or fenestrated thoracic endovascular aortic repair for aortic arch pathologies was assessed. Baseline characteristics, procedural fenestrated thoracic endovascular aortic repair, and outcome were analyzed. Furthermore, the potential anatomic feasibility of the respective alternate device was assessed on the preoperative computed tomography scans. RESULTS: The branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair cohorts consisted of 20 and 34 patients, respectively, with similar comorbidities; indication was aneurysm in 65% and 79%, penetrating aortic ulcer in 20% and 9%, and dissection in the remaining procedures, respectively. Technical success was achieved in all but 1 patient. Perioperative mortality and major stroke rate were both 10% in branched thoracic endovascular aortic repair and 0% and 3% in fenestrated thoracic endovascular aortic repair, respectively. During follow-up of 31 and 40 months, 1 branch occlusion occurred in the branched thoracic endovascular aortic repair cohort, and 2 late endoleaks occurred in the fenestrated thoracic endovascular aortic repair group. One aortic death occurred. Although 35% of patients undergoing branched thoracic endovascular aortic repair were anatomically suitable for fenestrated thoracic endovascular aortic repair, 91% of those undergoing fenestrated thoracic endovascular aortic repair were suitable for branched thoracic endovascular aortic repair. CONCLUSIONS: Both branched thoracic endovascular aortic repair and fenestrated thoracic endovascular aortic repair show excellent technical success and acceptable complication rates, whereas branched thoracic endovascular aortic repair tends toward higher morbidity, especially stroke rates. By offering fenestrated thoracic endovascular aortic repair along with branched thoracic endovascular aortic repair, aortic centers could potentially lower complication rates and simultaneously still treat a wide range of anatomies.

Structural failure in bridging stentgrafts for branched endovascular aneurysm repair: a case-control study.

OBJECTIVE: To present a case series of spontaneous structural failure of bridging stentgrafts (BSGs) after branched endovascular aortic repair (bEVAR), as well as their failure types and their detection. While bEVAR is a safe and effective procedure, one main limitation is the reintervention rate associated with the BSGs. Structural failure of BSGs, defined as fabric disruption, stent fracture with leak or complete separation is a major cause for reinterventions and difficult to detect in computed tomography angiography (CTA). METHODS: From a multicenter bEVAR complication database, structural BSG failures were identified. Patient and BSG characteristics, detection mode, failure type, treatment and outcome were recorded and compared with bEVAR patients with intact BSGs. RESULTS: Twenty-three BSG failures were detected in 12 patients with only 43% directly identified in CTA, after a mean of 21.4 months after implantation. The BSGs were Advanta (n = 4), E-Ventus (n = 16) and BeGraft (n = 3) in 10 renal, 9 superior mesenteric, and 4 celiac branches. Religning with another BSG was successful in 20/22 cases, one BSG failure necessitated renal branch embolization (organ loss), and one mesenteric bypass surgery. Two reintervention-related mortalities occurred. CONCLUSION: Structural failure of BSGs is a serious limitation for bEVAR, which can result in high reintervention rates and serious complications. BSG failure typically occurs in single-layer types and events are clustered in patients. The necessary reinterventions carry serious morbidity and mortality. Since the use as BSG in bEVAR is off-label with all current BSG manufacturers, caution is advised regarding patient-informed consent.

Endovascular Stent-Graft Repair of the Ascending Aorta: Assessment of a Specific Novel Stent-Graft Design in Phantom, Cadaveric, and Clinical Application.

PURPOSE: To test a stent-graft specifically designed for the ascending aorta in phantom, cadaver, and clinical application, and to measure deployment accuracy to overcome limitations of existing devices. METHODS: A stent-graft has been designed with support wires to fixate the apices toward the inner curvature, thereby eliminating the forward movement of the proximal end which can happen with circumferential tip capture systems. The device was deployed in three aortic phantoms, and in four cadavers, deployment precision was measured. Subsequently, the device was implanted in a patient to exclude a pseudoaneurysm originating from the distal anastomosis after ascending aortic replacement. RESULTS: The stent-grafts were successfully deployed in all phantoms and cadavers. Deployment accuracy of the proximal end of the stent-graft was within 1 mm proximally and 14 mm distally to the intended landing zone on the inner curvature, and 2-8 mm distal to the intended landing zone on the outer curvature. In clinical application, the pseudoaneurysm could be successfully excluded without complications. CONCLUSION: The novel stent-graft design promises accurate placement in the ascending aorta. The differential deployment of the apices at the inner and outer curvatures allows deployment perpendicular to the aortic axis. LEVEL OF EVIDENCE: No level of evidence.

Physiological modeling of isoprene dynamics in exhaled breath.

Human breath contains a myriad of endogenous volatile organic compounds (VOCs) which are reflective of ongoing metabolic or physiological processes. While research into the diagnostic potential and general medical relevance of these trace gases is conducted on a considerable scale, little focus has been given so far to a sound analysis of the quantitative relationships between breath levels and the underlying systemic concentrations. This paper is devoted to a thorough modeling study of the end-tidal breath dynamics associated with isoprene, which serves as a paradigmatic example for the class of low-soluble, blood-borne VOCs. Real-time measurements of exhaled breath under an ergometer challenge reveal characteristic changes of isoprene output in response to variations in ventilation and perfusion. Here, a valid compartmental description of these profiles is developed. By comparison with experimental data it is inferred that the major part of breath isoprene variability during exercise conditions can be attributed to an increased fractional perfusion of potential storage and production sites, leading to higher levels of mixed venous blood concentrations at the onset of physical activity. In this context, various lines of supportive evidence for an extrahepatic tissue source of isoprene are presented. Our model is a first step towards new guidelines for the breath gas analysis of isoprene and is expected to aid further investigations regarding the exhalation, storage, transport and biotransformation processes associated with this important compound.

Reduction of CPR artifacts in the ventricular fibrillation ECG by coherent line removal.

BACKGROUND: Interruption of cardiopulmonary resuscitation (CPR) impairs the perfusion of the fibrillating heart, worsening the chance for successful defibrillation. Therefore ECG-analysis during ongoing chest compression could provide a considerable progress in comparison with standard analysis techniques working only during "hands-off" intervals. METHODS: For the reduction of CPR-related artifacts in ventricular fibrillation ECG we use a localized version of the coherent line removal algorithm developed by Sintes and Schutz. This method can be used for removal of periodic signals with sufficiently coupled harmonics, and can be adapted to specific situations by optimal choice of its parameters (e.g., the number of harmonics considered for analysis and reconstruction). Our testing was done with 14 different human ventricular fibrillation (VF) ECGs, whose fibrillation band lies in a frequency range of [1 Hz, 5 Hz]. The VF-ECGs were mixed with 12 different ECG-CPR-artifacts recorded in an animal experiment during asystole. The length of each of the ECG-data was chosen to be 20 sec, and testing was done for all 168 = 14 x 12 pairs of data. VF-to-CPR ratio was chosen as -20 dB, -15 dB, -10 dB, -5 dB, 0 dB, 5 dB and 10 dB. Here -20 dB corresponds to the highest level of CPR-artifacts. RESULTS: For non-optimized coherent line removal based on signals with a VF-to-CPR ratio of -20 dB, -15 dB, -10 dB, -5 dB and 0 dB, the signal-to-noise gains (SNR-gains) were 9.3 +/- 2.4 dB, 9.4 +/- 2.4 dB, 9.5 +/- 2.5 dB, 9.3 +/- 2.5 dB and 8.0 +/- 2.7 (mean +/- std, n = 168), respectively. Characteristically, an original VF-to-CPR ratio of -10 dB, corresponds to a variance ratio var(VF):var(CPR) = 1:10. An improvement by 9.5 dB results in a restored VF-to-CPR ratio of -0.5 dB, corresponding to a variance ratio var(VF):var(CPR) = 1:1.1, the variance of the CPR in the signal being reduced by a factor of 8.9. DISCUSSION: The localized coherent line removal algorithm uses the information of a single ECG channel. In contrast to multi-channel algorithms, no additional information such as thorax impedance, blood pressure, or pressure exerted on the sternum during CPR is required. Predictors of defibrillation success such as mean and median frequency of VF-ECGs containing CPR-artifacts are prone to being governed by the harmonics of the artifacts. Reduction of CPR-artifacts is therefore necessary for determining reliable values for estimators of defibrillation success. CONCLUSIONS: The localized coherent line removal algorithm reduces CPR-artifacts in VF-ECG, but does not eliminate them. Our SNR-improvements are in the same range as offered by multichannel methods of Rheinberger et al., Husoy et al. and Aase et al. The latter two authors dealt with different ventricular rhythms (VF and VT), whereas here we dealt with VF, only. Additional developments are necessary before the algorithm can be tested in real CPR situations.

Additional Value of 2-[18F]FDG PET/CT Comparing to MRI in Treatment Approach of Anal Cancer Patients.

Accurate staging and treatment planning are imperative for precise management in Anal Cancer (ACa) patients. We aimed to evaluate the additive and prognostic value of pre-treatment 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the staging and management of ACa compared to magnetic resonance imaging (MRI). This retrospective study was conducted on 54 patients. Pre-treatment 2-[18F]FDG PET/CT studies and MRI reports were compared considering the primary tumor, pelvic lymph nodes, and metastatic lesions. The impact of 2-[18F]FDG PET/CT in the management and its prognostic value, using maximum standardized uptake value (SUVmax), were assessed. Discordant findings were found in 46.3% of patients (5 in T; 1 in T and N; 18 in N; and 1 in M stage). 2-[18F]FDG PET/CT resulted in up-staging in 9.26% and down-staging in 3.7% of patients. Perirectal lymph nodes were metabolically inactive in 12.9% of patients. Moreover, 2-[18F]FDG PET/CT resulted in management change in 24.1% of patients. Finally, SUVmax provided no prognostic value. 2-[18F]FDG PET/CT altered staging and management in a sizable number of patients in this study, and supports a need for a change in guidelines for it to be used as a routine complementary test in the initial management of ACa.

Measurement of endogenous acetone and isoprene in exhaled breath during sleep.

This explorative study aims at characterizing the breath behavior of two prototypic volatile organic compounds, acetone and isoprene, during normal human sleep and to possibly relate changes in the respective concentration time courses to the underlying sleep architecture. For this purpose, six normal healthy volunteers (two females, four males, age 20-29 years) were monitored over two consecutive nights (the first one being an adaption night) by combining real-time proton-transfer-reaction mass spectrometry measurements from end-tidal exhalation segments with laboratory-based polysomnographic data. Breath acetone concentrations increased overnight in all measurements, with an average relative change by a factor of up to 4 (median 2.5). Nighttime concentration maxima were usually recorded 2-3 h before lights on. For breath isoprene, a nocturnal increase in baseline concentrations of about 74% was observed, with individual changes ranging from 36-110%. Isoprene profiles exhibited pronounced concentration peaks, which were highly specific for leg movements as scored by tibial electromyography. Furthermore, relative to a linear trend, baseline isoprene concentrations decreased during the transition from the NREM to the REM phase of a complete sleep cycle.

Measurement of isoprene solubility in water, human blood and plasma by multiple headspace extraction gas chromatography coupled with solid phase microextraction.

The aim of this study was to determine the solubility (liquid-to-air ratios) of isoprene in water, human blood and plasma. To this end, an experimental setup combining multiple headspace extraction, solid phase microextraction and gas chromatography-mass spectrometry was applied. The water:air partition coefficients of isoprene were determined for the temperature range 4.5-37 °C and amounted to 1.171-0.277 (g mL(l)(-1)) (g mL(a)(-1))(-1). On the basis of these data, the enthalpy of volatilization was calculated as 29.46 ± 2.83 kJ mol(-1). The blood:air partition coefficients at 37 °C were determined for ten normal healthy volunteers spread around a median value of 0.95 ± 0.09 (g mL(l)(-1)) (g mL(a)(-1))(-1) and were approximately 16% lower than the plasma:air partition coefficients (1.11 ± 0.2). The applied methodology can be particularly attractive for solubility studies targeting species at very low concentrations in the solution, i.e. when headspace sample enrichment is necessary to provide sufficient measurement sensitivity and reliability. This can be especially helpful if environmental or physiological solute levels have to be considered.