Interclavicularis anticus digastricus muscle in a female body donor: a case report.

BACKGROUND AND OBJECTIVES: Muscular variations of the ventral thoracic wall are generally common and of great clinical interest. MATERIALS AND METHODS: An unusual muscular variation of the ventral thoracic wall was observed and dissected in a West-European female body donor. RESULTS: An interclavicularis anticus digastricus muscle was observed and studied. It originated from the manubrium sterni and inserted bilaterally to the clavicles. Both muscle bellies were interconnected by a tendon on the ventral surface of the manubrium sterni. The muscle was innervated by branches of the lateral pectoral nerve. CONCLUSIONS: The interclavicularis anticus digastricus muscle is a muscular variation of the ventral thoracic wall of unknown prevalence. This variation might be of clinical interest in orthopaedics and thoracic surgery. It is also a vulnerable structure during infraclavicular insertion of a subclavian vein catheter or fractures of the clavicle.

DNA damage and repair in peripheral blood mononuclear cells after internal ex vivo irradiation of patient blood with 131I.

AIM: The aim of this study was to provide a systematic approach to characterize DNA damage induction and repair in isolated peripheral blood mononuclear cells (PBMCs) after internal ex vivo irradiation with [131I]NaI. In this approach, we tried to mimic ex vivo the irradiation of patient blood in the first hours after radioiodine therapy. MATERIAL AND METHODS: Blood of 33 patients of two centres was collected immediately before radioiodine therapy of differentiated thyroid cancer (DTC) and split into two samples. One sample served as non-irradiated control. The second sample was exposed to ionizing radiation by adding 1 ml of [131I]NaI solution to 7 ml of blood, followed by incubation at 37 °C for 1 h. PBMCs of both samples were isolated, split in three parts each and (i) fixed in 70% ethanol and stored at - 20 °C directly (0 h) after irradiation, (ii) after 4 h and (iii) 24 h after irradiation and culture in RPMI medium. After immunofluorescence staining microscopically visible co-localizing γ-H2AX + 53BP1 foci were scored in 100 cells per sample as biomarkers for radiation-induced double-strand breaks (DSBs). RESULTS: Thirty-two of 33 blood samples could be analysed. The mean absorbed dose to the blood in all irradiated samples was 50.1 ± 2.3 mGy. For all time points (0 h, 4 h, 24 h), the average number of γ-H2AX + 53BP1 foci per cell was significantly different when compared to baseline and the other time points. The average number of radiation-induced foci (RIF) per cell after irradiation was 0.72 ± 0.16 at t = 0 h, 0.26 ± 0.09 at t = 4 h and 0.04 ± 0.09 at t = 24 h. A monoexponential fit of the mean values of the three time points provided a decay rate of 0.25 ± 0.05 h-1, which is in good agreement with data obtained from external irradiation with γ- or X-rays. CONCLUSION: This study provides novel data about the ex vivo DSB repair in internally irradiated PBMCs of patients before radionuclide therapy. Our findings show, in a large patient sample, that efficient repair occurs after internal irradiation with 50 mGy absorbed dose, and that the induction and repair rate after 131I exposure is comparable to that of external irradiation with γ- or X-rays.

α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients.

PURPOSE: One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. METHODS: Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. RESULTS: The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h - 4 weeks after administration), the α-track frequency remained elevated. CONCLUSION: The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from ß-emitters based on damage geometry.

Cardiogenic oscillations to detect intratidal derecruitment and overdistension in a porcine model of healthy and atelectatic lungs.

BACKGROUND: Low positive end-expiratory pressure (PEEP) can result in alveolar derecruitment, and high PEEP or high tidal volume (VT) in lung overdistension. We investigated cardiogenic oscillations (COS) in the airway pressure signal to investigate whether these oscillations can assess unfavourable intratidal events. COS induce short instantaneous compliance increases within the pressure-volume curve, and consequently in the compliance-volume curve. We hypothesised that increases in COS-induced compliance reflect non-linear intratidal respiratory system mechanics. METHODS: In mechanically ventilated anaesthetised pigs with healthy (n=13) or atelectatic (n=12) lungs, pressure-volume relationships and the ECG were acquired at a PEEP of 0, 5, 10, and 15 cm H2O. During inspiration, the peak compliance of successive COS (CCOS) was compared with intratidal respiratory system compliance (CRS) within incremental volume steps up to the full VT of 12 ml kg-1. We analysed whether CCOS variation corresponded with systolic arterial pressure variation. RESULTS: CCOS-volume curves showed characteristic intratidal patterns depending on the PEEP level and on atelectasis. Increasing CRS- or CCOS-volume patterns were associated with intratidal derecruitment with low PEEP, and decreasing patterns above 6 ml kg-1 and high PEEP showed overdistension. CCOS was not associated with systolic arterial pressure variations. CONCLUSIONS: Heartbeat-induced oscillations within the course of the inspiratory pressure-volume curve reflect non-linear intratidal respiratory system mechanics. The analysis of these cardiogenic oscillations can be used to detect intratidal derecruitment and overdistension and, hence, to guide PEEP and VT settings that are optimal for respiratory system mechanics.

Comparative usability of modern anaesthesia ventilators: a human factors study.

BACKGROUND: The anaesthesia ventilator represents the key equipment for intraoperative respiratory care. Improper operation of this device may threaten a patient's health. A self-explanatory interface facilitates handling and decreases the risk of operating errors. This study systematically evaluates the usability of user interfaces in four modern anaesthesia ventilators. METHODS: Twenty naïve operators were asked to execute 20 tasks on each of four different anaesthesia ventilators (Avance CS2™, GE Healthcare; Flow-i™, Maquet; and Perseus™ and Primus™, Dräger) in a randomized order. The success of task execution, frequency of requests for assistance, and processing times were recorded. During the tasks, the operators' visual focus was measured via eye-tracking. Additionally, subjective assessments of usability were evaluated by a standardized questionnaire. For comparison, six experienced operators undertook the same protocol. RESULTS: The overall rate of falsely executed tasks was low. Naïve operators requested assistance least when using the Perseus (26). Pooled processing times were shortest for the Perseus (222 s), followed by the Primus (223 s), the Avance (238 s), and the Flow-i (353 s). Task-specific processing times differed considerably between the devices. Eye-tracking analyses revealed associated interface issues that impeded the operators' performance. Operators rated usability best for the Perseus [mean (sd): 67 (17) arbitrary units] and worst for the Flow-i [50 (16) arbitrary units]. Results from experienced operators support these findings by trend. CONCLUSIONS: The usability of modern anaesthesia ventilators differs considerably. Interface issues of specific tasks impair the operator's efficiency. Eliminating the specific usability issues might improve the operator's performance and, as a consequence, the patient's safety.

Clinical on-site monitoring of ß-lactam antibiotics for a personalized antibiotherapy.

An appropriate antibiotherapy is crucial for the safety and recovery of patients. Depending on the clinical conditions of patients, the required dose to effectively eradicate an infection may vary. An inadequate dosing not only reduces the efficacy of the antibiotic, but also promotes the emergence of antimicrobial resistances. Therefore, a personalized therapy is of great interest for improved patients' outcome and will reduce in long-term the prevalence of multidrug-resistances. In this context, on-site monitoring of the antibiotic blood concentration is fundamental to facilitate an individual adjustment of the antibiotherapy. Herein, we present a bioinspired approach for the bedside monitoring of free accessible ß-lactam antibiotics, including penicillins (piperacillin) and cephalosporins (cefuroxime and cefazolin) in untreated plasma samples. The introduced system combines a disposable microfluidic chip with a naturally occurring penicillin-binding protein, resulting in a high-performance platform, capable of gauging very low antibiotic concentrations (less than 6 ng ml-1) from only 1 µl of serum. The system's applicability to a personalized antibiotherapy was successfully demonstrated by monitoring the pharmacokinetics of patients, treated with ß-lactam antibiotics, undergoing surgery.

Intraoperative compliance profiles and regional lung ventilation improve with increasing positive end-expiratory pressure.

BACKGROUND: Anaesthesia and mechanical ventilation can lead to impaired lung. Intraoperative positive end-expiratory pressure (PEEP) should prevent intratidal recruitment/derecruitment without causing overdistension. The intratidal compliance profile indicates both unwanted phenomena. We hypothesized that a higher than usual PEEP improves the intratidal compliance and the regional lung ventilation of patients with healthy lungs. METHODS: After ethics approval, 30 adult patients scheduled for limb surgery were investigated at PEEP 5, 7 and 9 cm H2 O during mechanical ventilation. We calculated the dynamic compliance of the respiratory system (CRS ) and the intratidal volume-dependent CRS curve. The CRS curve indicated intratidal recruitment/derecruitment and/or overdistension. Regional ventilation was measured using electrical impedance tomography. RESULTS: At PEEP 5, 7 and 9 cm H2 O, intratidal recruitment/derecruitment was observed in 92%, 84% and 46% (P < 0.05) of the patients respectively. Increasing PEEP was associated with recruitment in the dorsal regions of the lungs (P < 0.001). At PEEP 9 cm H2 O, lung overdistension was indicated in two patients. With PEEP levels up to 9 cm H2 O, no significant effects on haemodynamic variables were found. CONCLUSION: We conclude that in most patients, the often applied PEEP of 5 cm H2 O is insufficient to prevent intratidal recruitment/derecruitment and that few patients show overdistension at high PEEP levels. To establish optimal pressure-volume relationships in the respiratory system, the analysis of the individual intratidal compliance profiles could be a means for individualized perioperative PEEP titration.

Increasing positive end-expiratory pressure (re-)improves intraoperative respiratory mechanics and lung ventilation after prone positioning.

BACKGROUND: Turning a patient prone, changes the respiratory mechanics and potentially the level of positive end-expiratory pressure (PEEP) that is necessary to prevent alveolar collapse. In this prospective clinical study we examined the impact of PEEP on the intratidal respiratory mechanics and regional lung aeration in the prone position. We hypothesized that a higher PEEP is required to maintain compliance and regional ventilation in the prone position. METHODS: After ethical approval, 45 patients with healthy lungs undergoing lumbar spine surgery were examined in the supine position at PEEP 6 cm H2O and in the prone position at PEEP (6, 9 and 12 cm H2O). Dynamic compliance (CRS) and intratidal compliance-volume curves were determined and regional ventilation was measured using electrical impedance tomography. The compliance-volume curves were classified to indicate intratidal derecruitment, overdistension, or neither. RESULTS: CRS did not differ between postures and PEEP levels (P>0.28). At a PEEP of 6 cm H2O a compliance-volume profile indicating neither derecruitment nor overdistension was observed in 38 supine, but only in 20 prone positioned patients (P<0.001). The latter increased to 33 and 37 (both P<0.001) when increasing PEEP to 9 and 12 cm H2O, respectively. Increasing PEEP from 6 to 9 cm H2O in the prone position increased peripheral ventilation significantly. CONCLUSIONS: Respiratory system mechanics change substantially between supine and prone posture, which is not demonstrated in routine measurements. The intratidal compliance analysis suggests that in most patients a PEEP above commonly used settings is necessary to avoid alveolar collapse in the prone position. CLINICAL TRIAL REGISTRATION: DRKS 00005692.

Double-lumen tubes and auto-PEEP during one-lung ventilation.

BACKGROUND: Double-lumen tubes (DLT) are routinely used to enable one-lung-ventilation (OLV) during thoracic anaesthesia. The flow-dependent resistance of the DLT's bronchial limb may be high as a result of its narrow inner diameter and length, and thus potentially contribute to an unintended increase in positive end-expiratory pressure (auto-PEEP). We therefore studied the impact of adult sized DLTs on the dynamic auto-PEEP during OLV. METHODS: In this prospective clinical study, dynamic auto-PEEP was determined in 72 patients undergoing thoracic surgery, with right- and left-sided DLTs of various sizes. During OLV, air trapping was provoked by increasing inspiration to expiration ratio from 1:2 to 2:1 (five steps). Based on measured flow rate, airway pressure (Paw) and bronchial pressure (Pbronch), the pressure gradient across the DLT (ΔPDLT) and the total auto-PEEP in the respiratory system (i.e. the lungs, the DLT and the ventilator circuit) were determined. Subsequently the DLT's share in total auto-PEEP was calculated. RESULTS: ΔPDLT was 2.3 (0.7) cm H2O over the entire breathing cycle. At the shortest expiratory time the mean total auto-PEEP was 2.9 (1.5) cm H2O (range 0-5.9 cm H2O). The DLT caused 27 to 31% of the total auto-PEEP. Size and side of the DLT's bronchial limb did not impact auto-PEEP significantly. CONCLUSIONS: Although the DLT contributes to the overall auto-PEEP, its contribution is small and independent of size and side of the DLT's bronchial limb. The choice of DLT does not influence the risk of auto-PEEP during OLV to a clinically relevant extent. CLINICAL TRIAL REGISTRATION: DRKS00005648.

Biomechanical validation of computer assisted planning of periacetabular osteotomy: A preliminary study based on finite element analysis.

Periacetabular Osteotomy (PAO) is a joint preserving surgical intervention intended to increase femoral head coverage and thereby to improve stability in young patients with hip dysplasia. Previously, we developed a CT-based, computer-assisted program for PAO diagnosis and planning, which allows for quantifying the 3D acetabular morphology with parameters such as acetabular version, inclination, lateral center edge (LCE) angle and femoral head coverage ratio (CO). In order to verify the hypothesis that our morphology-based planning strategy can improve biomechanical characteristics of dysplastic hips, we developed a 3D finite element model based on patient-specific geometry to predict cartilage contact stress change before and after morphology-based planning. Our experimental results demonstrated that the morphology-based planning strategy could reduce cartilage contact pressures and at the same time increase contact areas. In conclusion, our computer-assisted system is an efficient tool for PAO planning.

Claudin-3, claudin-7, and claudin-10 show different distribution patterns during decidualization and trophoblast invasion in mouse and human.

Implantation of the mammalian embryo requires profound endometrial changes for successful pregnancy, including epithelial-mesenchymal transition of the luminal epithelium and stromal-epithelial transition of the stromal cells resulting in decidualization. Claudins (Cldn) determine the variability in tight junction paracellular permeability and may play a role during these epithelial and decidual changes. We here localized Cldn3, Cldn7 and Cldn10 proteins in the different compartments of murine endometrium up to day 8.5 of pregnancy (dpc) as well as in human endometrium and first trimester decidua. In murine estrous endometrium, luminal and glandular epithelium exhibited Cldn3 and Cldn7, whereas Cldn10 was only detectable in glandular epithelium. At 4.5 dpc, Cldn3 protein shifted to an apical localization, whereas Cldn7 vanished in the epithelium of the implantation chamber. At this stage, there was no stromal signal for Cldn3 and Cldn7, but a strong induction of Cldn10 in the primary decidual zone. Cldn3 proteins emerged at 5.5 dpc spreading considerably from 6.5 dpc onward in the endothelial cells of the decidual blood sinusoids and in the decidual cells of the compact antimesometrial region. In addition to Cldn3, Cldn10 was identified in human endometrial epithelia. Both proteins were not detected in human first trimester decidual cells. Cldn3 was shown in murine trophoblast giant cells as well as in human extravillous trophoblast cells and thus may have an impact on trophoblast invasion in both species. We here showed a specific claudin signature during early decidualization pointing to a role in decidual angiogenesis and regulation of trophoblast invasion.

Intraoperative positive end-expiratory pressure evaluation using the intratidal compliance-volume profile.

BACKGROUND: Lung-protective mechanical ventilation during general surgery including the application of PEEP can reduce postoperative pulmonary complications. In a prospective clinical observation study, we evaluated volume-dependent respiratory system compliance in adult patients undergoing ear-nose-throat surgery with ventilation settings chosen empirically by the attending anaesthetist. METHODS: In 40 patients, we measured the respiratory variables during intraoperative mechanical ventilation. All measurements were subdivided into 5 min intervals. Dynamic compliance (CRS) and the intratidal volume-dependent CRS curve was calculated for each interval and classified into one of the six specific compliance profiles indicating intratidal recruitment/derecruitment, overdistension or all. We retrospectively compared the occurrences of the respective compliance profiles at PEEP levels of 5 cm H2O and at higher levels. RESULTS: The attending anaesthetists set the PEEP level initially to 5 cm H2O in 29 patients (83%), to 7 cm H2O in 5 patients (14%), and to 8 cm H2O in 2 patients (6%). Across all measurements the mean CRS was 61 (11) ml cm H2O(-1) (40-86 ml cm H2O(-1)) and decreased continuously during the procedure. At PEEP of 5 cm H2O the compliance profile indicating strong intratidal recruitment/derecruitment occurred more often (18.6%) compared with higher PEEP levels (5.5%, P<0.01). Overdistension was practically never observed. CONCLUSIONS: In most patients, a PEEP of 5 cm H2O during intraoperative mechanical ventilation is too low to prevent intratidal recruitment/derecruitment. The analysis of the intratidal compliance profile provides the rationale to individually titrate a PEEP level that stabilizes the alveolar recruitment status of the lung during intraoperative mechanical ventilation. TRIAL REGISTRATION NUMBER: DRKS00004286.

Flow-controlled expiration: a novel ventilation mode to attenuate experimental porcine lung injury.

BACKGROUND: Whereas the effects of various inspiratory ventilatory modifications in lung injury have extensively been studied, those of expiratory ventilatory modifications are less well known. We hypothesized that the newly developed flow-controlled expiration (FLEX) mode provides a means of attenuating experimental lung injury. METHODS: Experimental acute respiratory distress syndrome was induced by i.v. injection of oleic acid in 15 anaesthetized and mechanically ventilated pigs. After established lung injury ([Formula: see text]ratio <27 kPa), animals were randomized to either a control group receiving volume-controlled ventilation (VCV) or a treatment group receiving VCV with additional FLEX (VCV+FLEX). At predefined times, lung mechanics and oxygenation were assessed. At the end of the experiment, the pigs were killed, and bronchoalveolar fluid and lung biopsies were taken. Expression of inflammatory cytokines was analysed in lung tissue and bronchoalveolar fluid. Lung injury score was determined on the basis of stained tissue samples. RESULTS: Compared with the control group (VCV; n=8), the VCV+FLEX group (n=7) demonstrated greater dynamic lung compliance and required less PEEP at comparable [Formula: see text] (both P<0.05), had lower regional lung wet-to-dry ratios and lung injury scores (both P<0.001), and showed less thickening of alveolar walls (an indicator of interstitial oedema) and de novo migration of macrophages into lung tissue (both P<0.001). CONCLUSIONS: The newly developed FLEX mode is able to attenuate experimental lung injury. FLEX could provide a novel means of lung-protective ventilation.

Monitoring of intratidal lung mechanics: a Graphical User Interface for a model-based decision support system for PEEP-titration in mechanical ventilation.

In mechanical ventilation, a careful setting of the ventilation parameters in accordance with the current individual state of the lung is crucial to minimize ventilator induced lung injury. Positive end-expiratory pressure (PEEP) has to be set to prevent collapse of the alveoli, however at the same time overdistension should be avoided. Classic approaches of analyzing static respiratory system mechanics fail in particular if lung injury already prevails. A new approach of analyzing dynamic respiratory system mechanics to set PEEP uses the intratidal, volume-dependent compliance which is believed to stay relatively constant during one breath only if neither atelectasis nor overdistension occurs. To test the success of this dynamic approach systematically at bedside or in an animal study, automation of the computing steps is necessary. A decision support system for optimizing PEEP in form of a Graphical User Interface (GUI) was targeted. Respiratory system mechanics were analyzed using the gliding SLICE method. The resulting shapes of the intratidal compliance-volume curve were classified into one of six categories, each associated with a PEEP-suggestion. The GUI should include a graphical representation of the results as well as a quality check to judge the reliability of the suggestion. The implementation of a user-friendly GUI was successfully realized. The agreement between modelled and measured pressure data [expressed as root-mean-square (RMS)] tested during the implementation phase with real respiratory data from two patient studies was below 0.2 mbar for data taken in volume controlled mode and below 0.4 mbar for data taken in pressure controlled mode except for two cases with RMS < 0.6 mbar. Visual inspections showed, that good and medium quality data could be reliably identified. The new GUI allows visualization of intratidal compliance-volume curves on a breath-by-breath basis. The automatic categorisation of curve shape into one of six shape-categories provides the rational decision-making model for PEEP-titration.

Determination of respiratory system mechanics during inspiration and expiration by FLow-controlled EXpiration (FLEX): a pilot study in anesthetized pigs.

BACKGROUND: Differences between inspiratory and expiratory lung mechanics result in the hysteresis of the pressure volume-loop. While hysteresis area is a global parameter describing the difference between inspiration and expiration in mechanics under quasi-static conditions, a detailed analysis of this difference under the dynamic conditions of mechanical ventilation is feasible once inspiratory and expiratory compliance (Cin/Cex) are determined separately. This requires uncoupling of expiratory flow rate and volume (V). METHODS: Five piglets were mechanically ventilated at positive end-expiratory pressure (PEEP) levels ranging from 0 to 15 cmH2O. Expiratory flow rate was linearized by a computer-controlled resistor (flow-controlled expiration). The volume-dependent Cin(V) and Cex(V) profiles were calculated from the tracheal pressure volume-loops. RESULTS: The intratidal curve-progression of Cex(V) was altogether higher with a steeper slope compared to Cin(V). With increasing positive end-expiratory pressure (PEEP) dynamic hysteresis area decreased and Cex(V) tended to run more parallel to Cin(V). CONCLUSION: The relation between inspiratory and expiratory compliance profiles is associated with the hysteresis area and behaves PEEP dependent. Analysing the Cin-Cex-relation might therefore potentially offer a new approach to titrate PEEP and tidal volume.