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Simple Summary: This multicenter study (n = 1133, inclusion criteria: 3.5 cm maximum tumor size and preoperative indication for a boost) provides detailed data on acute and long-term toxicities in breast cancer patients undergoing breast-conserving surgery combined with an anticipated intraoperative boost with low-energy X-rays followed by whole breast irradiation. Toxicity assessments, based on LENT SOMA criteria, were performed annually up to 10 years of follow-up. IORT boost was completed in 90% and EBRT in 97% of cases. No grade 3 or 4 acute toxicities were observed, with mild acute side effects reported in a small proportion of patients. Chronic toxicities were seen in 16.2% of patients with teleangiectasia, 14.3% with grade ≥ 2 fibrosis, 3.4% with grade ≥ 2 pain, and 1.1% with hyperpigmentation. The results show that the therapy is safe and feasible in terms of toxicity and confirms intraoperative boost as a standard method of boost application in a large prospective cohort. In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1–120, 20.4% dropped out), with a median age of 61 years (range 30–90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation. [ABSTRACT FROM AUTHOR]

Objective: Fetal magnetic resonance imaging (MRI) is broadly used as a method for assessing prognosis in congenital diaphragmatic hernia (CDH). In addition to the extent of lung hypoplasia, determined by measuring the lung volume, cardiac impairment due to pulmonary hypertension and left cardiac hypoplasia is decisive for the prognosis. The percentage area of left ventricle (pALV) describes the percentage of the inner area of the left ventricle in relation to the total area, whereas the mediastinal shift angle (MSA) quantifies the extent of cardiac displacement. The prognostic value of pALV and MSA should be evaluated in terms of survival, the need for extracorporeal membrane oxygenation (ECMO) therapy, and the development of chronic lung disease (CLD). Methods: In a total of 122 fetal MRIs, the MSA and pALV were measured retrospectively and complete outcome parameters were determined regarding survival for all 122 subjects, regarding ECMO therapy in 109 cases and about the development of CLD in 78 cases. The prognostic value regarding the endpoints was evaluated using logistic regression and ROC analysis. Results: The MSA was significantly higher in children who received ECMO therapy (p = 0.0054), as well as in children who developed CLD (p = 0.0018). ROC analysis showed an AUC of 0.68 for ECMO requirement and 0.77 with respect to CLD development. The pALV showed a tendency towards higher levels in children who received ECMO therapy (p = 0.0824). The MSA and the pALV had no significant effect on survival (MSA: p = 0.4293, AUC = 0.56; pALV: p = 0.1134, AUC = 0.57). Conclusions: The MSA determined in fetal MRI is a suitable prognostic parameter for ECMO requirement and CLD development in CDH patients and can possibly be used as a supplement to the established parameters. [ABSTRACT FROM AUTHOR]

The primary aim of this study was to assess the incidence of a difficult airway and emergency tracheostomy in patients with orofacial infections originating in the mandible, and a secondary aim was to determine the potential predictors of difficult intubation. This retrospective single-center study included all patients who were referred between 2015 and 2022 with an orofacial infection originating in the mandible and who were surgically drained under intubation anesthesia. The incidence of a difficult airway regarding ventilation, laryngoscopy, and intubation was analyzed descriptively. Associations between potential influencing factors and difficult intubation were examined via multivariable analysis. A total of 361 patients (mean age: 47.7 years) were included in the analysis. A difficult airway was present in 121/361 (33.5%) patients. Difficult intubation was most common in patients with infections of the massetericomandibular space (42.6%), followed by infections of the mouth floor (40%) and pterygomandibular space (23.5%). Dyspnea and stridor were not associated with the localization of infection (p = 0.6486/p = 0.4418). Multivariable analysis revealed increased age, restricted mouth opening, higher Mallampati scores, and higher Cormack–Lehane classification grades as significant predictors of difficult intubation. Higher BMI, dysphagia, dyspnea, stridor and a non-palpable mandibular rim did not influence the airway management. Patients with a difficult airway were more likely to be admitted to the ICU after surgery than patients with regular airway were (p = 0.0001). To conclude, the incidence of a difficult airway was high in patients with orofacial infections originating in the mandible. Older age, limited mouth opening, a higher Mallampati score, and a higher Cormack–Lehane grade were reliable predictors of difficult intubation. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine the factors influencing the development of recurrence after the surgical treatment of odontogenic maxillary sinusitis in an oral and maxillofacial surgery clinic over a 7-year period. Demographic and anamnesis data, clinical and radiological findings, treatment and outcome were analyzed. A multivariable analysis was performed to find associations between patient age, causative focus, surgical access for sinus revision, multilayer closure with a buccal fat pad, inferior meatal antrostomy (IMA) for temporary sinus drainage and sinusitis recurrence. A total of 164 patients with a mean age of 51.7 years were included. Sinusitis recurrence was observed in nine patients (5.48%) within 6 months after primary surgery. No significant correlation was detected between patient age, causative focus, surgical access for sinus revision, multilayer closure with a buccal fat pad, IMA for sinus drainage and the development of recurrence (p > 0.05). Patients with a history of antiresorptive-related osteonecrosis of the jaw showed a significant tendency toward disease recurrence (p = 0.0375). In conclusion, except for antiresorptive administration, none of the investigated variables were related to a higher risk of sinusitis recurrence. We encourage a combined approach of intraoral removal of the infective focus and sinus drainage via FESS, as well as an individual treatment decision in a multidisciplinary setting with collaboration between dentistry, maxillofacial surgery and otorhinolaryngology to avoid sinusitis recurrence. [ABSTRACT FROM AUTHOR]

The primary aim was to evaluate the compliance of cranial CT indication with the national guideline-based decision rules in patients after mTBI. The secondary aim was to determine the incidence of CT pathologies among justified and unjustified CT scans and to investigate the diagnostic value of these decision rules. This is a retrospective, single-center study on 1837 patients (mean age = 70.7 years) referred to a clinic of oral and maxillofacial surgery following mTBI over a five-year period. The current national clinical decision rules and recommendations for mTBI were retrospectively applied to calculate the incidence of unjustified CT imaging. The intracranial pathologies among the justified and unjustified CT scans were presented using descriptive statistical analysis. The performance of the decision rules was ascertained by calculating the sensitivity, specificity, and predictive values. A total of 123 intracerebral lesions were radiologically detected in 102 (5.5%) of the study patients. Most (62.1%) of the CT scans strictly complied with the guideline recommendations, and 37.8% were not justified and likely avoidable. A significantly higher incidence of intracranial pathology was observed in patients with justified CT scans compared with patients with unjustified CT scans (7.9% vs. 2.5%, p < 0.0001). Patients with loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of cranial fractures presented pathologic CT findings more frequently (p < 0.05). The decision rules identified CT pathologies with 92.28% sensitivity and 39.08% specificity. To conclude, compliance with the national decision rules for mTBI was low, and more than a third of the CT scans performed were identified as "likely avoidable". A higher incidence of pathologic CT findings was detected in patients with justified cranial CT imaging. The investigated decision rules showed a high sensitivity but low specificity for predicting CT pathologies. [ABSTRACT FROM AUTHOR]

The primary aim was to determine the clinical indicators for primary cranial CT imaging in patients after mild traumatic brain injury (mTBI). The secondary aim was to evaluate the need for post-traumatic short-term hospitalization based on primary clinical and CT findings. This was an observational retrospective single-centre study of all the patients who were admitted with mTBI over a five-year period. Demographic and anamnesis data, the clinical and radiological findings, and the outcome were analyzed. An initial cranial CT (CT0) was performed at admission. Repeat CT scans (CT1) were performed after positive CT0 findings and in cases with in-hospital secondary neurological deterioration. Intracranial hemorrhage (ICH) and the patient's outcome were evaluated using descriptive statistical analysis. A multivariable analysis was performed to find associations between the clinical variables and the pathologic CT findings. A total of 1837 patients (mean age: 70.7 years) with mTBI were included. Acute ICH was detected in 102 patients (5.5%), with a total of 123 intracerebral lesions. In total, 707 (38.4%) patients were admitted for 48 h for in-hospital observation and six patients underwent an immediate neurosurgical intervention. The prevalence of delayed ICH was 0.05%. A Glasgow Coma Scale (GCS) of <15, loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of fracture were identified as clinical factors with significantly higher risk of acute ICH. None of the 110 CT1 presented clinical relevance. A GCS of <15, loss of consciousness, amnesia, seizures, cephalgia, somnolence, dizziness, nausea, and clinical signs of cranial fractures should be considered absolute indicators for primary cranial CT imaging. The reported incidence of immediate and delayed traumatic ICH was very low and hospitalization should be decided individually considering both the clinical and CT findings. [ABSTRACT FROM AUTHOR]

Simple Summary: There is still a lack of reliable molecular predictors to achieve major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) in the therapeutic management of newly diagnosed chronic myeloid leukemia (CML). Employing a proprietary fluorogenic flow cytometry assay, we recently identified separase proteolytic activity as a potential marker of molecular response and BCR::ABL1 positivity of CD34+ cells in TKI-treated CML patients. Here, we analyzed the expression and predictive value of ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin interacting protein transcript levels in white blood cells of CML patients (n = 97) at the time of diagnosis by means of qRT-PCR. We establish a novel distance (cut-off) score based on ESPL1, PTTG1 and PTTG1IP gene expression levels that can serve as predictors of TKI non-response in about 10% of analyzed non-responding patients and may have potential benefit for the risk stratification of CML patients. The achievement of major molecular response (MMR, BCR::ABL1 ≤ 0.1% IS) within the first year of treatment with tyrosine kinase inhibitors (TKI) is a milestone in the therapeutic management of patients with newly diagnosed chronic myeloid leukemia (CML). We analyzed the predictive value of gene expression levels of ESPL1/Separase, PTTG1/Securin and PTTG1IP/Securin interacting protein for MMR achievement within 12 months. Relative expression levels (normalized to GUSB) of ESPL1, PTTG1 and PTTG1IP in white blood cells of patients (responders n = 46, non-responders n = 51) at the time of diagnosis were comparatively analyzed by qRT-PCR. 3D scatter plot analysis combined with a distance analysis performed with respect to a commonly calculated centroid center resulted in a trend to larger distances for non-responders compared to the responder cohort (p = 0.0187). Logistic regression and analysis of maximum likelihood estimates revealed a positive correlation of distance (cut-off) with non-achieving MMR within 12 months (p = 0.0388, odds ratio 1.479, 95%CI: 1.020 to 2.143). Thus, 10% of the tested non-responders (cut-off ≥ 5.9) could have been predicted already at the time of diagnosis. Future scoring of ESPL1, PTTG1 and PTTG1IP transcript levels may be a helpful tool in risk stratification of CML patients before initiation of TKI first = line treatment. [ABSTRACT FROM AUTHOR]

The human central nervous system (CNS) is separated from the blood by distinct cellular barriers, including the blood–brain barrier (BBB) and the blood–cerebrospinal fluid (CFS) barrier (BCSFB). Whereas at the center of the BBB are the endothelial cells of the brain capillaries, the BCSFB is formed by the epithelium of the choroid plexus. Invasion of cells of either the BBB or the BCSFB is a potential first step during CNS entry by the Gram-positive bacterium Listeria monocytogenes (Lm). Lm possesses several virulence factors mediating host cell entry, such as the internalin protein family—including internalin (InlA), which binds E-cadherin (Ecad) on the surface of target cells, and internalin B (InlB)—interacting with the host cell receptor tyrosine kinase Met. A further family member is internalin (InlF), which targets the intermediate filament protein vimentin. Whereas InlF has been shown to play a role during brain invasion at the BBB, its function during infection at the BCSFB is not known. We use human brain microvascular endothelial cells (HBMEC) and human choroid plexus epithelial papilloma (HIBCPP) cells to investigate the roles of InlF and vimentin during CNS invasion by Lm. Whereas HBMEC present intracellular and surface vimentin (besides Met), HIBCPP cells do not express vimentin (except Met and Ecad). Treatment with the surface vimentin modulator withaferin A (WitA) inhibited invasion of Lm into HBMEC, but not HIBCPP cells. Invasion of Lm into HBMEC and HIBCPP cells is, however, independent of InlF, since a deletion mutant of Lm lacking InlF did not display reduced invasion rates. [ABSTRACT FROM AUTHOR]

Ureteral stenosis and urinary leakage are relevant problems after kidney transplantation. A standardized definition of ureterovesical anastomosis complications after kidney transplantation has not yet been established. This study was designed to demonstrate the predictive power of quantitative indocyanine green (ICG) fluorescence angiography. This bicentric historic cohort study, conducted between November 2015 and December 2019, included 196 kidney transplantations. The associations between quantitative perfusion parameters of near-infrared fluorescence angiography with ICG and the occurrence of different grades of ureterovesical anastomosis complications in the context of donor, recipient, periprocedural, and postoperative characteristics were evaluated. Post-transplant ureterovesical anastomosis complications occurred in 18%. Complications were defined and graded into three categories. They were associated with the time on dialysis (p = 0.0025), the type of donation (p = 0.0404), and the number of postoperative dialysis sessions (p = 0.0173). Median ICG ingress at the proximal ureteral third was 14.00 (5.00–33.00) AU in patients with and 23.50 (4.00–117.00) AU in patients without complications (p = 0.0001, cutoff: 16 AU, sensitivity 70%, specificity 70%, AUC = 0.725, p = 0.0011). The proposed definition and grading of post-transplant ureterovesical anastomosis complications is intended to enable valid comparisons between studies. ICG Fluorescence angiography allows intraoperative quantitative assessment of ureteral microperfusion during kidney transplantation and is able to predict the incidence of ureterovesical anastomosis complications. Registration number: NCT-02775838. [ABSTRACT FROM AUTHOR]

Background: The coefficient of friction (CoF) serves as an indicator for the mechanical properties of natural and regenerated articular cartilage (AC). After tribological exposure, a height loss (HL) of the cartilage pair specimens can be measured. Our aim was to determine the CoF and HL of regenerated AC tissue and compare them with those of natural AC from non-operated joints and AC from joints where the regenerated tissues had been created after different treatments. Methods: In partial-thickness defects of the trochleae of the stifle joints of 60 Göttingen Minipigs, regenerated AC was created. In total, 40 animals received a Col I matrix, 20 laden with autologous chondrocytes, and 20 without. The defects of 20 animals were left empty. The healing periods were 24 and 48 weeks. A total of 10 not-operated animals, delivered the "external" control specimens. Osteochondral pins were harvested from defect and non-defect areas, the latter serving as "internal" controls. Using a pin-on-plate tribometer, we measured the CoF and the HL. Results: The CoF of the regenerated AC ranged from 0.0393 to 0.0688, and the HL, from 0.22 mm to 0.3 mm. The differences between the regenerated AC of the six groups and the "external" controls were significant. The comparison with the "internal" controls revealed four significant differences for the CoF and one for the HL in the operated groups. No differences were seen within the operated groups. Conclusions: The mechanical quality of the regenerated AC tissue showed inferior behavior with regard to the CoF and HL in comparison with natural AC. The comparison of regenerated AC tissue with AC from untreated joints was more promising than with AC from the treated joints. [ABSTRACT FROM AUTHOR]

Simple Summary: In biomechanical research, fresh frozen cadaver material and embalmed specimens are often used to evaluate surgical approaches. Unlike, biomechanical research using fresh cadaver material is rare. There are no reliable data on the point of time when rigor mortis starts to have an impact on results with fresh cadaver material. In this study, the authors have conducted measurements using fresh porcine cadaver tendons of the supraspinatus muscle post mortem to determine the time of onset and the influence of rigor mortis on specimen tissue. 151 min post mortem, a significant decrease in tendon mobility was observed. Therefore, the authors of the presented study concluded that the onset of rigor mortis started 151 min post mortem and decreased the mobility of the tendon. Hence, biomechanical research using fresh cadaver material should ideally be conducted within 150 min post mortem to obtain in vivo-like results without being impacted by rigor mortis. (1) Many biomechanical studies are performed using fresh frozen cadavers or embalmed specimens, although the biomechanical characteristics do not match the characteristics of in vivo tendons. Therefore, a fresh in vivo-like cadaver model has been introduced recently. As a limitation for studies with fresh cadavers, rigor mortis must be considered. The aim of this study was to evaluate the impact of the biomechanical properties and time of occurrence of rigor mortis in a fresh cadaver model. (2) For this study, 15 fresh porcine cadaver shoulders were used in an established biomechanical in vitro model to evaluate the onset of rigor mortis. Measurements took place at ten points of time (t1–t10) beginning 103 min post mortem (pm). The mobility of the supraspinatus tendon was measured in Newton (N) with a modified sensor-enhanced arthroscopic grasper. (3) The mean load measured at the time point t1 was 28.0 ± 11.2 N. The first significant decrease of mobility occurred 151 min post mortem (t4) at a mean load of 30.2 ± 13.7 N. From 227 min pm to 317 min pm, there was no further significant increase. (4) Tendon mobility decreases significantly within the first three hours after the killing. Therefore, reliable results can be obtained within 150 min post mortem before the onset of rigor mortis alters the biomechanical properties. [ABSTRACT FROM AUTHOR]

Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 kidney recipients by visual and formal perfusion assessment, duplex sonography, and quantitative microperfusion assessment using O2C spectrometry and ICG fluorescence angiography. The O2C tissue spectrometry device provides a quantitative method of microperfusion assessment that can be employed during kidney transplantation as an easy-to-use and highly sensitive alternative to ICG fluorescence angiography. Intraoperative microvascular flow and velocity in the allograft cortex after reperfusion predicted DGF with a sensitivity of 100% and a specificity of 82%. Threshold values of 57 A.U. for microvascular flow and 13 A.U. for microvascular velocity were identified by an ROC analysis. This study, therefore, confirmed that impairment of microperfusion of the allograft cortex directly after reperfusion was a key indicator for the occurrence of DGF after kidney transplantation. Our results support the combined use of intraoperative duplex sonography, for macrovascular quality control, and quantitative microperfusion assessment, such as O2C spectrometry, for individual risk stratification to guide subsequent postoperative management. [ABSTRACT FROM AUTHOR]

One potential comorbidity after congenital diaphragmatic hernia (CDH) is gastroesophageal reflux (GER), which can have a substantial effect on patients' quality of life, thriving, and complications later in life. Efforts have been made to reduce gastroesophageal reflux with a preventive anti-reflux procedure at the time of CDH repair. In this follow-up study of neonates participating in a primary RCT study on preventive anti-reflux surgery, symptoms of GER were assessed longitudinally. Long-term data with a median follow-up time of ten years was available in 66 patients. Thirty-one neonates received an initial fundoplication. Secondary anti-reflux surgery was necessary in 18% and only in patients with large defects. It was required significantly more often in patients with intrathoracic herniation of liver (p = 0.015) and stomach (p = 0.019) and patch repair (p = 0.03). Liver herniation was the only independent risk factor identified in multivariate regression analysis. Primary fundopexy and hemifundoplication did not reveal a protective effect regarding the occurrence of GER symptoms, the need for secondary antireflux surgery or the gain of body weight regardless of defect size neither in the short nor in the long term. Symptoms of GER must be assessed carefully especially in children with large defects, as these are prone to require secondary anti-reflux surgery in the long-term. Routine evaluation of GER including endoscopy and impedance measurement should be recommended especially for high-risk patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Factors secreted from irradiated mesenchymal stromal cells (MSC) may exert genotoxic effects in human CD34+ cells, thereby potentially contributing to the pathogenesis of hematologic disorders such as leukemias. In a proteomics approach, we recently identified four key proteins in the secretome of X-ray-irradiated MSC, among them the three chaperones GRP78, CALR, and PDIA3, and one glycolytic enzyme GPI. Here, we demonstrate that recombinant GRP78, CALR, PDIA3 and GPI induce significant levels of genetic instability in human CD34+ cells. Our data suggest that GRP78, CALR, PDIA3 and GPI released from irradiated MSC act as mediators of genetic instability in human CD34+ cells with potential implications for radiation-induced hematologic disorders. Soluble factors released from irradiated human mesenchymal stromal cells (MSC) may induce genetic instability in human CD34+ cells, potentially mediating hematologic disorders. Recently, we identified four key proteins in the secretome of X-ray-irradiated MSC, among them three endoplasmic reticulum proteins, the 78 kDa glucose-related protein (GRP78), calreticulin (CALR), and protein disulfide-isomerase A3 (PDIA3), as well as the glycolytic enzyme glucose-6-phosphate isomerase (GPI). Here, we demonstrate that exposition of CD34+ cells to recombinant GRP78, CALR, PDIA3 and GPI induces substantial genetic instability. Increased numbers of γH2AX foci (p < 0.0001), centrosome anomalies (p = 0.1000) and aberrant metaphases (p = 0.0022) were detected in CD34+ cells upon incubation with these factors. Specifically, γH2AX foci were found to be induced 4–5-fold in response to any individual of the four factors, and centrosome anomalies by 3–4 fold compared to control medium, which contained none of the recombinant proteins. Aberrant metaphases, not seen in the context of control medium, were detected to a similar extent than centrosome anomalies across the four factors. Notably, the strongest effects were observed when all four factors were collectively provided. In summary, our data suggest that specific components of the secretome from irradiated MSC act as mediators of genetic instability in CD34+ cells, thereby possibly contributing to the pathogenesis of radiation-induced hematologic disorders beyond direct radiation-evoked DNA strand breaks. [ABSTRACT FROM AUTHOR]

Necrotizing enterocolitis (NEC) continues to cause high morbidity and mortality. Identifying early predictors for severe NEC is essential to improve therapy and optimize timing for surgical intervention. We present a retrospective study of patients with NEC, treated between 2010 and 2020, trying to identify factors influencing the severity of NEC. Within the study period, 88 affected infants with NEC or NEC-like symptoms are analyzed. A multiple logistic regression analysis reveals the following three independent predictors for NEC in Bell stage III: red blood cell transfusion (p = 0.027 with odds ratio (OR) = 3.298), sonographic findings (p = 0.037; OR = 6.496 for patients with positive vs. patients without pathological findings) and cardiac anatomy (p = 0.015; OR = 1.922 for patients with patent ductus arteriosus (PDA) vs. patients with congenital heart disease (CHD); OR = 5.478/OR = 2.850 for patients with CHD/PDA vs. patients without cardiac disease). Results are summarized in a clinical score for daily application in clinical routine. The score is easy to apply and combines clinically established parameters, helping to determine the timing of surgical intervention. [ABSTRACT FROM AUTHOR]

Background: In sarcopenic patients the skeletal muscle reduction is the primary symptom of age- or disease-related malnutrition, which is linked to postoperative morbidity and mortality. The skeletal muscle mass index (SMI) from magnet resonance imaging (MRI) is increasingly used as a prognostic factor in oncologic and surgical patients, but under-represented in the field of obesity surgery. The bioelectrical impedance analysis (BIA), on the other hand is a commonly used method for the estimation of the body composition of bariatric patients, but still believed to be inaccurate, because of patient-related and environmental factors. The aim of this study was to compare the postoperative SMI values as a direct, imaging measured indicator for muscle mass with the BIA results in patients undergoing Roux-en-Y gastric bypass (RYGB). Methods: We performed a prospective single-center trial. Patients undergoing RYGB between January 2010 and December 2011 at our institution were eligible for this study. MRI and BIA measurements were obtained 1 day before surgery and at 6, 12 and 24 weeks after surgery. Results: A total of 17 patients (four male, 13 female, average age of 41.9 years) were included. SMI values decreased significantly during the postoperative course (p < 0.001). Comparing preoperative and postoperative measurements at 24 weeks after surgery, increasing correlations of SMI values with body weight (r = 0.240 vs. r = 0.628), phase angle (r = 0.225 vs. r = 0.720) and body cell mass (BCM, r = 0.388 vs. r = 0.764) were observed. Conclusions: SMI decreases significantly after RYGB and is correlated to distinct parameters of body composition. These findings show the applicability of the SMI as direct imaging parameter for the measurement of the muscle mass in patients after RYGB, but also underline the important role of the BIA, as a precise tool for the estimation of patients' body composition at low costs. BIA allows a good overview of patients' status post bariatric surgery, including an estimation of sarcopenia. [ABSTRACT FROM AUTHOR]

We performed voxel-guided morphometry (VGM) investigating the mechanisms of brain atrophy in multiple sclerosis (MS) related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w) magnetic resonace imaging (MRI). Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL) (volume increase > 5% in VGM), chronic enlarging lesions (CEL) (pre-existent T1w lesions with volume increase > 5%), or chronic shrinking lesions (CSL) (pre-existent T1w lesions with volume reduction > 5%) in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL) contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain. [ABSTRACT FROM AUTHOR]

Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic vascular complications. Our aim was to identify whether hyperglycemia is able to amplify inflammation via Hb-Hp complex interactions with the immune system. M(IFNγ), M(IL-4), and control M0 macrophages were differentiated out of primary human monocytes in normo- (5 mM) and hyperglycemic (25 mM) conditions. CD163 gene expression was decreased 5.53 times in M(IFNγ) with a further decrease of 1.99 times in hyperglycemia. Hyperglycemia suppressed CD163 surface expression in M(IFNγ) (1.43 times). Flow cytometry demonstrated no impairment of Hb-Hp uptake in hyperglycemia. However, hyperglycemia induced an inflammatory response of M(IFNγ) to Hb-Hp1-1 and Hb-Hp2-2 uptake with different dynamics. Hb-Hp1-1 uptake stimulated IL-6 release (3.03 times) after 6 h but suppressed secretion (5.78 times) after 24 h. Contrarily, Hb-Hp2-2 uptake did not affect IL-6 release after 6h but increased secretion after 24 h (3.06 times). Our data show that hyperglycemia induces an inflammatory response of innate immune cells to Hb-Hp1-1 and Hb-Hp2-2 uptake, converting the silent Hb-Hp complex clearance that prevents vascular damage into an inflammatory process, hereby increasing the susceptibility of diabetic patients to vascular complications. [ABSTRACT FROM AUTHOR]

Febrile seizures (FS) affect up to 5% of children. The pathogen etiology in regard of viral loads has never been investigated. In a prospective cohort study we investigated the correlation between virus type and quantity in nasopharyngeal aspirates (NPAs) and the clinical characteristics in pediatric patients with a FS. From January 2014 to April 2016, 184 children with a FS were prospectively enrolled. The mean age of all included children was 26.7 ± 18.3 months with a male to female ratio of 1.4:1. Males with an acute disease and a short duration or absence of prior symptoms had a higher risk for complex FS. The majority of patients with FS presented with a generalized convulsion (180; 98%) and was admitted to hospital (178; 97%). Overall, 79 (43%) single and in 59 (32%) co-infections were detected. Human herpes virus 6 (HHV6), influenza, adenovirus (AV) and rhinovirus (RV) were the dominant pathogens, all detected with clinically significant high viral loads. HHV6 positive cases were significantly younger and less likely to have a positive family/personal history for FS. Influenza positives showed a higher rate of complex seizures, lower leukocyte and higher monocyte counts. AV positive cases were more likely to have a positive family history for FS and showed higher C-reactive protein values. In conclusion, a high viral load may contribute to the development of a FS in respiratory tract infections. [ABSTRACT FROM AUTHOR]

Non-targeted effects (NTE) of ionizing radiation may initiate myeloid neoplasms (MN). Here, protein mediators (I) in irradiated human mesenchymal stromal cells (MSC) as the NTE source, (II) in MSC conditioned supernatant and (III) in human bone marrow CD34+ cells undergoing genotoxic NTE were investigated. Healthy sublethal irradiated MSC showed significantly increased levels of reactive oxygen species. These cells responded by increasing intracellular abundance of proteins involved in proteasomal degradation, protein translation, cytoskeleton dynamics, nucleocytoplasmic shuttling, and those with antioxidant activity. Among the increased proteins were THY1 and GNA11/14, which are signaling proteins with hitherto unknown functions in the radiation response and NTE. In the corresponding MSC conditioned medium, the three chaperones GRP78, CALR, and PDIA3 were increased. Together with GPI, these were the only four altered proteins, which were associated with the observed genotoxic NTE. Healthy CD34+ cells cultured in MSC conditioned medium suffered from more than a six-fold increase in γH2AX focal staining, indicative for DNA double-strand breaks, as well as numerical and structural chromosomal aberrations within three days. At this stage, five proteins were altered, among them IQGAP1, HMGB1, and PA2G4, which are involved in malign development. In summary, our data provide novel insights into three sequential steps of genotoxic signaling from irradiated MSC to CD34+ cells, implicating that induced NTE might initiate the development of MN. [ABSTRACT FROM AUTHOR]

Genotoxic bystander signals released from irradiated human mesenchymal stromal cells (MSC) may induce radiation-induced bystander effects (RIBEs) in human hematopoietic stem and progenitor cells (HSPC), potentially causing leukemic transformation. Although the source of bystander signals is evident, the identification and characterization of these signals is challenging. Here, RIBEs were analyzed in human CD34+ cells cultured in distinct molecular size fractions of medium, conditioned by 2 Gy irradiated human MSC. Specifically, γH2AX foci (as a marker of DNA double-strand breaks) and chromosomal instability were evaluated in CD34+ cells grown in approximate (I) < 10 kDa, (II) 10–100 kDa and (III) > 100 kDa fractions of MSC conditioned medium and un-/fractionated control medium, respectively. Hitherto, significantly increased numbers of γH2AX foci (p = 0.0286) and aberrant metaphases (p = 0.0022) were detected in CD34+ cells grown in the (II) 10–100 kDa fraction (0.67 ± 0.10 γH2AX foci per CD34+ cell ∨ 3.8 ± 0.3 aberrant metaphases per CD34+ cell sample; mean ± SEM) when compared to (I) < 10 kDa (0.19 ± 0.01 ∨ 0.3 ± 0.2) or (III) > 100 kDa fractions (0.23 ± 0.04 ∨ 0.4 ± 0.4) or un-/fractionated control medium (0.12 ± 0.01 ∨ 0.1 ± 0.1). Furthermore, RIBEs disappeared after heat inactivation of medium at 75 °C. Taken together, our data suggest that RIBEs are mainly mediated by the heat-sensitive (II) 10–100 kDa fraction of MSC conditioned medium. We postulate proteins as RIBE mediators and in-depth proteome analyses to identify key bystander signals, which define targets for the development of next-generation anti-leukemic drugs. [ABSTRACT FROM AUTHOR]

In systemic mastocytosis (SM), qualitative and serial quantitative assessment of the KIT D816V mutation is of diagnostic and prognostic relevance. We investigated peripheral blood and bone marrow samples of 161 patients (indolent SM (ISM), n = 40; advanced SM, AdvSM, n = 121) at referral and during follow-up for the KIT D816V variant allele frequency (VAF) at the DNA-level and the KIT D816V expressed allele burden (EAB) at the RNA-level. A round robin test with four participating laboratories revealed an excellent correlation (r > 0.99, R2 > 0.98) between three different DNA-assays. VAF and EAB strongly correlated in ISM (r = 0.91, coefficient of determination, R2 = 0.84) but only to a lesser extent in AdvSM (r = 0.71; R2 = 0.5). However, as compared to an EAB/VAF ratio ≤2 (cohort A, 77/121 patients, 64%) receiver operating characteristic (ROC) analysis identified an EAB/VAF ratio of >2 (cohort B, 44/121 patients, 36%) as predictive for an advanced phenotype and a significantly inferior median survival (3.3 vs. 11.7 years; p = 0.005). In terms of overall survival, Cox-regression analysis was only significant for the EAB/VAF ratio >2 (p = 0.006) but not for VAF or EAB individually. This study demonstrates for the first time that the transcriptional activity of KIT D816V may play an important role in the pathophysiology of SM. [ABSTRACT FROM AUTHOR]

Simple Summary: Although introducing minimally invasive surgery reduced postoperative morbidity after esophagectomy esophageal cancer still is a malignancy with poor prognosis. This study aimed to investigate whether preoperative sarcopenia has an influence on short-term postoperative outcome after esophagectomy in esophageal cancer patients. Our findings suggest that preoperative sarcopenia is no independent prognostic factor for postoperative outcome after esophagectomy but that patients' nutritional status consists of more factors than only body mass index (BMI) and muscle mass. Prehabilitation and preoperative optimization of the patients' nutritional status seems to be an important factor for short-term postoperative outcome after esophagectomy. By introducing minimally invasive surgery the rate of postoperative morbidity in esophageal cancer patients could be reduced. But esophagectomy is still associated with a relevant risk of postoperative morbidity and mortality. Patients often present with nutritional deficiency and sarcopenia even at time of diagnosis. This study focuses on the influence of skeletal muscle index (SMI) on postoperative morbidity and mortality. Fifty-two patients were included in this study. SMI was measured using computer tomographic images at the time of diagnosis and before surgery. Then, SMI and different clinicopathological and demographic features were correlated with postoperative morbidity. There was no correlation between SMI before neoadjuvant therapy (p = 0.5365) nor before surgery (p = 0.3530) with the short-term postoperative outcome. Regarding cholesterol level before surgery there was a trend for a higher risk of complications with lower cholesterol levels (p = 0.0846). Our findings suggest that a low preoperative SMI does not necessarily predict a poor postoperative outcome in esophageal cancer patients after esophagectomy but that there are many factors that influence the nutritional status of cancer patients. To improve nutritional status, cancer patients at our clinic receive specialized nutritional counselling during neoadjuvant treatment as well as after surgery. [ABSTRACT FROM AUTHOR]

Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood–brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood–cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis. [ABSTRACT FROM AUTHOR]

Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on subsequent ALL transmigration across the barrier was studied in a human BCSFB in vitro model based on the HiBCPP cell line. The various cell lines markedly differed regarding exosome uptake to HiBCPP and biological significance. SD-1-derived exosomes associated to target cells unspecifically without detectable cellular effects. Whereas Nalm-6 and P12-derived exosomes incorporated by dynamin-dependent endocytosis, uptake in the latter could be diminished by integrin blocking. In addition, only P12-derived exosomes led to facilitated transmigration of the parental leukemia cells. In conclusion, we provide evidence that, to a varying extent, leukemia-derived exosomes may facilitate CNS invasion of ALL across the BCSFB without destruction of the barrier integrity. [ABSTRACT FROM AUTHOR]

Background: The aim is to compare the machine learning-based coronary-computed tomography fractional flow reserve (CT-FFRML) and coronary-computed tomographic morphological plaque characteristics with the resting full-cycle ratio (RFRTM) as a novel invasive resting pressure-wire index for detecting hemodynamically significant coronary artery stenosis. Methods: In our single center study, patients with coronary artery disease (CAD) who had a clinically indicated coronary computed tomography angiography (cCTA) and subsequent invasive coronary angiography (ICA) with pressure wire-measurement were included. On-site prototype CT-FFRML software and on-site CT-plaque software were used to calculate the hemodynamic relevance of coronary stenosis. Results: We enrolled 33 patients (70% male, mean age 68 ± 12 years). On a per-lesion basis, the area under the receiver operating characteristic curve (AUC) of CT-FFRML (0.90) was higher than the AUCs of the morphological plaque characteristics length/minimal luminal diameter4 (LL/MLD4; 0.80), minimal luminal diameter (MLD; 0.77), remodeling index (RI; 0.76), degree of luminal diameter stenosis (0.75), and minimal luminal area (MLA; 0.75). Conclusion: CT-FFRML and morphological plaque characteristics show a significant correlation to detected hemodynamically significant coronary stenosis. Whole CT-FFRML had the best discriminatory power, using RFRTM as the reference standard. [ABSTRACT FROM AUTHOR]

Background: Machine-learning-based computed-tomography-derived fractional flow reserve (CT-FFRML) obtains a hemodynamic index in coronary arteries. We examined whether it could reduce the number of invasive coronary angiographies (ICA) showing no obstructive lesions. We further compared CT-FFRML-derived measurements to clinical and CT-derived scores. Methods: We retrospectively selected 88 patients (63 ± 11years, 74% male) with chronic coronary syndrome (CCS) who underwent clinically indicated coronary computed tomography angiography (cCTA) and ICA. cCTA image data were processed with an on-site prototype CT-FFRML software. Results: CT-FFRML revealed an index of >0.80 in coronary vessels of 48 (55%) patients. This finding was corroborated in 45 (94%) patients by ICA, yet three (6%) received revascularization. In patients with an index ≤ 0.80, three (8%) of 40 were identified as false positive. A total of 48 (55%) patients could have been retained from ICA. CT-FFRML (AUC = 0.96, p ≤ 0.0001) demonstrated a higher diagnostic accuracy compared to the pretest probability or CT-derived scores and showed an excellent sensitivity (93%), specificity (94%), positive predictive value (PPV; 93%) and negative predictive value (NPV; 94%). Conclusion: CT-FFRML could be beneficial for clinical practice, as it may identify patients with CAD without hemodynamical significant stenosis, and may thus reduce the rate of ICA without necessity for coronary intervention. [ABSTRACT FROM AUTHOR]

DNA damage and alterations in the DNA damage response (DDR) are critical sources of genetic instability that might be involved in BCR-ABL1 kinase-mediated blastic transformation of chronic myeloid leukemia (CML). Here, increased DNA damage is detected by γH2AX foci analysis in peripheral blood mononuclear cells (PBMCs) of de novo untreated chronic phase (CP)-CML patients (n = 5; 2.5 γH2AX foci per PBMC ± 0.5) and blast phase (BP)-CML patients (n = 3; 4.4 γH2AX foci per PBMC ± 0.7) as well as CP-CML patients with loss of major molecular response (MMR) (n = 5; 1.8 γH2AX foci per PBMC ± 0.4) when compared to DNA damage in PBMC of healthy donors (n = 8; 1.0 γH2AX foci per PBMC ± 0.1) and CP-CML patients in deep molecular response or MMR (n = 26; 1.0 γH2AX foci per PBMC ± 0.1). Progressive activation of erroneous non-homologous end joining (NHEJ) repair mechanisms during blastic transformation in CML is indicated by abundant co-localization of γH2AX/53BP1 foci, while a decline of the DDR is suggested by defective expression of (p-)ATM and (p-)CHK2. In summary, our data provide evidence for the accumulation of DNA damage in the course of CML and suggest ongoing DNA damage, erroneous NHEJ repair mechanisms, and alterations in the DDR as critical mediators of blastic transformation in CML. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the impact of postoperative complications on overall survival (OS) after radical resection for gastric cancer. Methods: A retrospective analysis of our institutional database for surgical patients with gastroesophageal malignancies was performed. All consecutive patients who underwent R0 resection for M0 gastric cancer between October 1972 and February 2014 were included. The impact of postoperative complications on OS was evaluated in the entire cohort and in a subgroup after exclusion of 30 day and in-hospital mortality. Results: A total of 1107 patients were included. In the entire cohort, both overall complications (p < 0.001) and major surgical complications (p = 0.003) were significant risk factors for decreased OS in univariable analysis. In multivariable analysis, overall complications were an independent risk factor for decreased OS (p < 0.001). After exclusion of patients with complication-related 30 day and in-hospital mortality, neither major surgical (p = 0.832) nor overall complications (p = 0.198) were significantly associated with decreased OS. Conclusion: In this study, postoperative complications influenced OS due to complication-related early postoperative deaths. In patients successfully rescued from early postoperative complications, neither overall complications nor major surgical complications were risk factors for decreased survival. [ABSTRACT FROM AUTHOR]

Malignant hematopoietic cells of myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemias (CMML) and acute myeloid leukemias (AML) may be vulnerable to inhibition of poly(ADP ribose) polymerase 1/2 (PARP1/2) and apurinic/apyrimidinic endonuclease 1 (APE1). PARP1/2 and APE1 are critical enzymes involved in single-strand break repair and base excision repair, respectively. Here, we investigated the cytotoxic efficacy of talazoparib and APE1 inhibitor III, inhibitors of PARP1/2 and APE1, in primary CD34+ MDS/CMML cell samples (n = 8; 4 MDS and 4 CMML) and in primary CD34+ or CD34− AML cell samples (n = 18) in comparison to healthy CD34+ donor cell samples (n = 8). Strikingly, talazoparib and APE1 inhibitor III demonstrated critical antileukemic efficacy in selected MDS/CMML and AML cell samples. Low doses of talazoparib and APE1 inhibitor III further increased the cytotoxic efficacy of decitabine in MDS/CMML and AML cells. Moreover, low doses of APE1 inhibitor III increased the cytotoxic efficacy of talazoparib in MDS/CMML and AML cells. In summary, talazoparib and APE1 inhibitor III demonstrated substantial antileukemic efficacy as single agents, in combination with decitabine, and combined with each other. Hence, our findings support further investigation of these agents in sophisticated clinical trials. [ABSTRACT FROM AUTHOR]

Regulation of particular genes during the formation of neural crest (NC) cells is also described during progression of malignant melanoma. In this context, it is of paramount importance to develop neural crest models allowing the identification of candidate genes, which could be used as biomarkers for melanoma prognosis. Here, we used a human induced Pluripotent Stem Cells (iPSC)-based approach to present novel NC-associated genes, expression of which was upregulated in melanoma. A list of 8 candidate genes, based on highest upregulation, was tested for prognostic value in a tissue microarray analysis containing samples from advanced melanoma (good versus bad prognosis) as well as from high-risk primary melanomas (early metastasizing versus non or late-metastasizing). CD271, GLDC, and ERRFI1 showed significantly higher expression in metastatic patients who died early than the ones who survived at least 30 months. In addition, GLDC and TWIST showed a significantly higher immunohistochemistry (IHC) score in primary melanomas from patients who developed metastases within 12 months versus those who did not develop metastases in 30 months. In conclusion, our iPSC-based study reveals a significant association of NC marker GLDC protein expression with melanoma prognosis. [ABSTRACT FROM AUTHOR]

Background and objectives: The laryngeal mask is the method of choice for airway management in children during minor surgical procedures. There is a paucity of data regarding optimal management of mechanical ventilation in these patients. The Supreme™ airway laryngeal mask offers the option to insert a gastric tube to empty the stomach contents of air and/or gastric juice. The aim of this investigation was to evaluate the impact of positive end-expiratory positive pressure (PEEP) levels on ventilation parameters and gastric air insufflation during general anesthesia in children using pressure-controlled ventilation with laryngeal mask. Materials and Methods: An observational trial was carried out in 67 children aged between 1 and 11 years. PEEP levels of 0, 3 and 5 mbar were tested for 5 min in each patient during surgery and compared with ventilation parameters (dynamic compliance (mL/cmH 2 O), etCO 2 (mmHg), peak pressure (mbar), tidal volume (mL), respiratory rate (per minute), FiO 2 and gastric air (mL)) were measured at each PEEP. Air was aspirated from the stomach at the start of the sequence of measurements and at the end. Results : Significant differences were observed for the ventilation parameters: dynamic compliance (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001), peak pressure (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001) and tidal volume (PEEP 5 vs. PEEP 3: p = 0.0048, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001). All parameters increased significantly with higher PEEP, with the exception of etCO 2 (significant decrease) and respiratory rate (no significant difference). We also showed different values for air quantity in the comparisons between the different PEEP levels (PEEP 5: 2.8 ± 3.9 mL, PEEP 3: 1.8 ± 3.0 mL; PEEP 0: 1.6 ± 2.3 mL) with significant differences between PEEP 5 and PEEP 3 ( p = 0.0269) and PEEP 5 and PEEP 0 ( p = 0.0209). Conclusions : Our data suggest that ventilation with a PEEP of 5 mbar might be more lung protective in children using the Supreme™ airway laryngeal mask, although gastric air insufflation increased with higher PEEP. We recommend the use of a laryngeal mask with the option of inserting a gastric tube to evacuate potential gastric air.