BACKGROUNDPositive end-expiratory pressure (PEEP) is important to increase lung volume and counteract airway closure during anaesthesia, especially in obese patients. However, maintaining PEEP during emergence preoxygenation might increase postoperative atelectasis by allowing susceptible lung areas to be filled with highly absorbable oxygen that gets entrapped when small airways collapse due to the sudden loss of PEEP at extubation.OBJECTIVEThis study aimed to test the hypothesis that withdrawing PEEP just before emergence preoxygenation would better maintain postoperative oxygenation.DESIGNProspective, randomised controlled trial.SETTINGSingle centre secondary hospital in Sweden between December 2019 and January 2023.PATIENTSA total of 60 patients, with body mass index between 35 and 50 kg m-2, undergoing laparoscopic bariatric surgery.INTERVENTIONIntraoperative ventilation was the same for all patients with a fixed PEEP of 12 or 14 cmH2O depending on body mass index. No recruitment manoeuvres were used. After surgery, patients were allocated to maintained PEEP or zero PEEP during emergence preoxygenation.MAIN OUTCOME MEASURESThe primary outcome was change in oxygenation from before awakening to 45 min postoperatively as measured by estimated venous admixture calculated from arterial blood gases.RESULTSBoth groups had impaired oxygenation postoperatively; in the group with PEEP maintained during awakening, estimated venous admixture increased by mean 9.1%, and for the group with zero PEEP during awakening, estimated venous admixture increased by mean 10.6%, difference -1.5% (95% confidence interval -4.6 to 1.7%), P = 0.354. Throughout anaesthesia, both groups exhibited low driving pressures and superior oxygenation compared with the awake state.CONCLUSIONSWithdrawing PEEP before emergence preoxygenation, did not alter early postoperative oxygenation in obese patients undergoing laparoscopic bariatric surgery. Intraoperative oxygenation was excellent despite using fixed PEEP and no recruitment manoeuvres, but deteriorated after extubation, indicating a need for future studies aimed at improving the emergence procedure.CLINICAL TRIAL NUMBER AND REGISTRYwww.clinicaltrials.gov, NCT 04150276.

BACKGROUND The prerequisites for the early formation of anaesthesia-related atelectasis are pre-oxygenation with its resulting high alveolar oxygen content, and airway closure. Airway closure increases with age, so it seems counterintuitive that atelectasis formation during anaesthesia does not. One proposed explanation is that pre-oxygenation is impaired in the elderly by airway closure present in the waking state. The extent of airway closure cannot be assessed at the bedside, but arterial partial pressure of oxygen (P aO2) as a surrogate variable of the resulting ventilation to perfusion mismatch can. OBJECTIVE The primary aim was to test the hypothesis that a decreased efficacy of pre-oxygenation, measured as the fraction of end-tidal oxygen (FE’O2) after 3 min of pre-oxygenation, correlates with decreased P aO2 on room air. We also re-investigated the influence on FE’O2 by age. DESIGN Prospective observational study. SETTING Two regional hospitals, Västerås and Köping County Hospitals, Västmanland, Sweden, between 30 October 2018 and 17 September 2021. PARTICIPANTS We included 120 adults aged 40 to 79 years presenting for elective noncardiac surgery. INTERVENTION An arterial blood gas was sampled before commencing pre-oxygenation. RESULTS No linear correlation was found between FE’O2 at 3 min and P aO2 or age (Pearson's r = −0.038, P = 0.684; and Pearson's r = −0.113, P = 0.223, respectively). The mean ± SD FE’O2 at 3 min for the population studied was 0.87 ± 0.05. CONCLUSION The lack of correlation between FE’O2 at 3 min and P aO2 or age during pre-oxygenation has implications for further studies concerning the interaction between airway closure and atelectasis. After 3 min of pre-oxygenation, FE’O2, even in the elderly, indicated a high enough alveolar oxygen concentration to promote atelectasis after induction, therefore, it is still unclear why atelectasis formation diminishes after middle age. TRIAL REGISTRATION ClinicalTrials.gov NCT03395782

Background Plasma levels of cell - free DNA (cf-DNA) are known to be elevated in sepsis and high levels are associated with a poor prognosis. Mechanical ventilation affects systemic inflammation in which lung-protective ventilation attenuates the inflammatory response. The aim was to study the effect of a lung protective ventilator regime on arterial and organ-specific venous blood as well as on trans-organ differences in cf-DNA levels in a porcine post-operative sepsis model. Method One group of anaesthetised, domestic-breed, 9–12 weeks old, pigs were ventilated with protective ventilation (V T 6 mL x kg − 1 , PEEP 10 cmH 2 O) n = 20. Another group, ventilated with a medium high tidal volume and lower PEEP, served as a control group (V T 10 mL x kg − 1 , PEEP 5 cm H 2 O) n = 10. Blood samples were taken from four sources: artery, hepatic vein, portal vein and, jugular bulb. A continuous endotoxin infusion at 0.25 μg x kg − 1 x h − 1 for 5 h was started following 2 h of laparotomy, which simulated a surgical procedure. Inflammatory cytokines and cf-DNA in plasma were analysed and trans-organ differences calculated. Results The protective ventilation group had lower levels of cf-DNA in arterial ( p = 0.02) and hepatic venous blood ( p = 0.03) compared with the controls. Transhepatic differences in cf-DNA were lower in the protective group, compared with the controls ( p = 0.03). No differences between the groups were noted as regards the transcerebral, transsplanchnic or the transpulmonary cf-DNA differences. Conclusions Protective ventilation suppresses arterial levels of cf-DNA. The liver seems to be a net contributor to the systemic cf-DNA levels, but this effect is attenuated by protective ventilation.

Background: Great advances have been made in the molecular characterisation of advanced breast cancer (ABC). Still, clinical practice has not changed in terms of assessment of response to therapy. Radiologic imaging and clinical examination help determine disease burden and treatment efficacy. However, imaging heavily relies on the expertise of the radiologist and oncologist and has high intra- and inter-reader variability. Circulating tumor cells (CTCs) enumeration with CellSearchâ has confirmed independent prognostic value compared to conventional radiology and serum markers such as CA15-3. Similarly, quantification of circulating tumor DNA (ctDNA) has also prognostic value in ABC. ctDNA analysis further provides critical information on the mutational status of specific genes which can predict sensitivity to specific targeted therapeutics. Trial design: The SCAN-B-rec (NCT03758976) is a prospective multi-center observational study that aims to explore the value provided by ctDNA analysis to determine treatment efficacy when compared to CTCs and conventional radiological imaging in a "real-world" setting. A total of 350 patients with pathologically-confirmed ABC will be recruited. Plasma ctDNA will be extracted and analysed before treatment start (T0) and after three months of therapy (T1). The relative change in mutant allele frequency (MAF) between these two time-points will be calculated. Response to treatment will be defined using pre-specified cut-offs. A comparison with response to treatment according to conventional radiological imaging (RECIST criteria) and CTC enumeration at the same time points will be performed. The primary objective is to establish the prognostic value of ctDNA to predict overall survival. The study will also explore the added value provided by ctDNA mutational analysis to determine biomarkers of sensitivity and resistance to targeted therapeutics approved to treat ABC or other solid tumors that could be used "off-label". We expect that ctDNA quantification will give a more accurate read-out of treatment response, providing better prognostic information in ABC as well as information on drug sensitivity/resistance in a large proportion of ABC patients. Clinical trial identification: SCAN-B-rec (NCT03758976). Legal entity responsible for the study: Lund University Hospital (Region Skane). Funding: BioCARE, Cancer Fonden, ALF (Region Skåne) and Svenska Läkaresällskapet. Disclosure: A. Bosch: Advisory board meetings: Pfizer, Novartis in Sweden. These have been non-remunarated. L. Saal: CEO: AGA Diagnostics. All other authors have declared no conflicts of interest.

High-Resolution Time-Resolved Phase-Contrast Synchrotron CT for Mapping Cardiac-Induced Lung Motion

Abstract Background: Detection and enumeration of circulating tumor cells (CTCs) allows real time monitoring of disease evolvement. In women with metastatic breast cancer (MBC), a CTC count of ≥5 CTCs is associated with decreased progression-free survival (PFS) and overall survival (OS). Serial sampling after therapy initiation has indicated that longitudinal CTC enumeration adds prognostic information, but data from long time sampling is sparse. The aim of this study was to evaluate if prospective longitudinal detection of CTC count and CTC clusters in women with newly diagnosed MBC can improve prognostication and monitoring of patients in the clinical setting. Methods: Longitudinal blood samples were collected at baseline (BL) and after 1, 3 and 6 months in 156 women with MBC scheduled for 1st line systemic therapy. CTC enumeration and cluster detection were performed by the CellSearch® system in a prospective monitoring trial (NCT01322893). 115 patients had evaluable samples at all time-points. Primary endpoint was PFS and secondary endpoint was OS at BL in relation to CTC count and as landmark analyses during treatment. In addition, change in CTC count during therapy was compared to progressive disease (PD) versus non-PD. Structured clinical and radiological evaluation for PD was performed every 3rd month. Results: Seventy-nine (52%) of 152 evaluable patients had ≥5 CTC and 14/79 patients had CTC-clusters (33 clustered CTC) at BL. Median follow-up time was 25 (7-69) months. Patients with ≥5 CTCs had inferior PFS and OS in uni-(data not shown) and multivariable analysis (HRPFS 1.91 (1.26-2.91), P=0.003) (HROS 3.57 (2.02-6.31), P<0.001) at BL. Presence of clusters at BL was prognostic for OS (HROS 2.37 (1.25-4.51), P=0.008). Longitudinal landmark analysis of number of CTCs and presence of CTC clusters showed a time-dependent increase in HR during treatment for CTCs and CTC-clusters and predicted worse PFS and OS at all time-points. Stratifying patients based on CTC count and presence of clusters revealed four risk groups (0, 1-4, ≥5 CTC, ≥5 CTC + clusters) where patients with clusters had inferior PFS and OS at all time points. Change in CTC count from BL to 1 and 3 months, and from 3 to 6 months was significantly related to evaluation at 3 and 6 months (PD vs non-PD, P=0.013 (3 months), P=0.016 (6 months)) and change in CTC count from BL to 1, 3 and 6 months was also significantly predictive of both PFS and OS. Notably, survival was significantly inferior for patients with persistent CTC ≥5 during treatment. Discussion: CTC is an independent prognostic factor for MBC patients scheduled for 1st line systemic therapy. By longitudinal monitoring during treatment, the prognostic information by presence of ≥5 CTC and clusters increases over time and supports long time monitoring of patients. Importantly, detection of CTC-clusters identifies a subgroup of patients with dismal prognosis at all time-points indicating that CTC-clusters renders important clinical information. Change in CTC count during systemic therapy is related to outcome of evaluation and prognosis at all time-points. Citation Format: Larsson A-M, Jansson S, Bendahl P-O, Baker S, Graffman C, Lundgren C, Loman N, Aaltonen KE, Rydén L. Improved prognostic information by serial monitoring of CTC enumeration and CTC-clusters from baseline to six months in patients with metastatic breast cancer scheduled for 1st line systemic therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-01-03.

Acta Psychiatrica ScandinavicaVolume 135, Issue 3 p. 266-267 Letter to the Editor Anxiolytic effect of warmth in anorexia nervosa M. Zandian, M. Zandian Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorE. Holmstedt, E. Holmstedt Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorA. Larsson, A. Larsson Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorC. Bergh, C. Bergh Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorU. Brodin, U. Brodin Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorP. Södersten, P. Södersten per.sodersten@ki.se Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this author M. Zandian, M. Zandian Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorE. Holmstedt, E. Holmstedt Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorA. Larsson, A. Larsson Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorC. Bergh, C. Bergh Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorU. Brodin, U. Brodin Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this authorP. Södersten, P. Södersten per.sodersten@ki.se Karolinska Institutet, Section of Applied Neuroendocrinology, Mandometer Clinic, Huddinge, SwedenSearch for more papers by this author First published: 02 January 2017 https://doi.org/10.1111/acps.12691Citations: 13Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume135, Issue3March 2017Pages 266-267 RelatedInformation

The presence of circulating tumor cells (CTCs) in the blood of patients with breast cancer is by now a well-recognized prognosticator for poor prognosis but the selection of systemic therapy based on characteristics of CTCs is still under investigation. We present methods to characterize CTCs with respect to protein biomarker expression and genomic changes in individually selected CTCs. Blood samples spiked with cell line cells (SKBr3, MCF7, BT474, Colo205) were used for method optimization and all applications were further validated in patient samples from the CTC-MBC study of metastatic breast cancer (Clinical Trials NCT01322893). CTCs were enriched with the FDA-approved CellSearch® system (Janssen Diagnostics) and subsequently fixated on glass slides using the CTC-DropMount method. Here, we present additional applications for characterization of fixated CTCs. We have established a multiplex fluorescence staining procedure for detection of the established treatment predictive markers human epidermal growth factor receptor 2 (HER2) and estrogen receptor α (ERα), concurrent with positive and negative staining for CTCs according to a pre-defined evaluation protocol. In addition, we have now optimized fluorescence staining for programmed death-ligand 1 (PD-L1) expression on CTCs. This marker is suggested to be associated with response to immune checkpoint regulators. A protocol for HER2 gene amplification analysis has also been established using fluorescence in situ hybridization (FISH). Moreover, we have isolated individually selected CTCs using laser capture microdissection (PALM MicroBeam, Zeiss). Following whole genome amplification of the selected cells, the DNA quality suggests that a variety of genomic analyses could be employed to further characterize CTCs with regard to treatment predictive mutations, as well as to increase our understanding of tumor evolution. CTCs are easily accessible in patient blood samples and could be used for further improvement of treatment selection as well as for monitoring treatment response. We have optimized methods to characterize CTCs following enrichment with the CellSearch® system. Clinical trial identification: Verification of the methods presented in the abstract has been performed in patient samples from the CTC-MBC study (Clinical Trials NCT01322893). Legal entity responsible for the study: N/A Funding: The Swedish Research Council, The Cancer Foundation, Governmental ALF-funding, Leander's Foundation, BioCare Disclosure: All authors have declared no conflicts of interest.

Objective: To explore the relationship between blood pressure categories at baseline and incident hypertension at follow-up in a representative Swedish population. Design and method: A longitudinal study over 10 years in a Swedish population. Main measures were anthropometric data, blood pressure, fasting glucose, LDL, CRP, eGFR, current smoking, leisure time physical activity and medical history. Blood pressures were measured and categorized according to ESH guidelines with optimal blood pressure defined as < 120 mmHg systolic and < 80 mmHg diastolic, normal as 120–129/80–84 mmHg, high normal as 130–139/85–89 mmHg, and unstable as >=140 and/or >=90 mmHg at one or two visits but not on three. Hypertension was defined as ongoing treatment or readings of >=140 and/or >= 90 mmHg at three consecutive visits. Subjects with hypertension at baseline were excluded. Data were analyzed with multivariate binary logistics regression. Results: Among the 1129 participating subjects the proportion with optimal blood pressure at the baseline survey was 56.1% (n=633), normal blood pressure 25.9% (n = 292), high normal blood pressure 12.5% (n = 141), and unstable blood pressure 5.6% (n = 63), respectively. Of those with optimal blood pressure at baseline 18 (2.8%), converted to hypertension during follow up. Corresponding numbers for subjects with normal, high normal and unstable blood pressure were 58 (19.9%), 56 (39.7%) and 47 (74.6%) respectively. Both normal, high normal and unstable baseline blood pressure were associated with an increased risk of development to manifest hypertension compared to optimal blood pressure, with odds ratios (OR (95% CI)) of 5.4 (CI 2.9–9.9), 12.5 (CI 6.3–25) and 88 (CI 33–231), respectively, independent of age and other main cardiovascular risk factors. A trend test showed that the OR for incident hypertension per unit of baseline blood pressure category was 3.8 (CI 2.9–5.0). The progression to hypertension was also independently predicted by age, BMI and heredity for hypertension. Conclusions: Subjects with high normal or unstable blood pressure should be identified in clinical practice and evaluated for global risk accounting for family history of hypertension. Measures should be taken to avoid or postpone the development of hypertension and its complications.

We addressed whether endothelin-1, a marker of endothelial dysfunction, predicts impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in a population study in south-western Sweden. Follow-up after 9.7 years showed an association between circulating endothelin-1 levels at baseline and development of IGT/T2DM in women but not in men.

Objective: Small artery elasticity index (SAEI) have been associated with incident hypertension and incident cardiovascular disease (CVD), independent of relevant risk factors. The aim of this study was to investigate the association between the intensity of LTPA and SAEI at baseline and at follow-up in a prospective design. Design and method: In this longitudinal observational study, a representative cohort (2816 individuals, ∼50% male) in southwestern Sweden, aged 35–75 at baseline was followed for 9.7 ± 1.4 years. Of these, a representative subpopulation of 1062 individuals (534 women and 528 men) had complete information at baseline and follow-up. SAEI, assessed using HDI/Pulse wave CR-2000 (Eagan, MN), and anthropometric were collected at baseline and at follow up. The change in mean SAEI between baseline and follow-up was calculated as (SAEI1-SAEI2)/((SAEI1 + SAEI2)/2). Diabetes was assessed using OGTT and physician diagnosis based on WHO 1999, while hypertension was defined based on JNC7. Information regarding lifestyle was collected using validated questionnaires. The initial 4 levels of self-reported LTPA were dichotomized into two categories: sedentary (level 1–2) and physically active (level 3–4). General linear models with adjustments for possible confounders were used to assess differences between categories. Results: At baseline (after adjustment for age, sex, systolic blood pressure, use of blood pressure lowering drugs, diabetes, waist hip ratio, HOMA-IR and smoking), the sedentary group had significantly lower SAEI than the physically active group (7.85 vs 8.33 ml/mmHg, p < 0.01). Using the same model, similar differences were observed at the follow-up visit (sedentary = 6.56 vs. active = 7.07, p < 0.01). Although a significant decrease in SAEI was observed in the whole group over the follow-up period (from 8.0 to 6.7 ml/mmHg, p < 0.001), the change in SAEI was similar in the two LTPA groups (sedentary = 0.19 vs active = 0.18, p = 0.75). Conclusions: In this cohort, the level of physical activity at baseline did not influence the decrease in SAEI. However, moderate to intensive LTPA was associated with higher SAEI and this association persisted during follow up. These results suggest a long-term beneficial effect of LTPA on the vascular function.