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Aim: The real-world benefits of continuous glucose monitoring (CGM) in the broad type 2 diabetes (T2D) population are not well studied. Our study evaluated the impact of CGM use on health care resource utilization over 12 months in adults with T2D., Materials and Methods: This retrospective cohort analysis used Optum's de-identified Market Clarity data of >79 million people to evaluate CGM use in people with T2D who were treated with non-insulin (NIT), basal insulin (BIT) and prandial insulin therapy (PIT). The primary outcomes were changes in all-cause hospitalizations, acute diabetes-related hospitalizations and acute diabetes-related emergency room visits during the 6- and 12-month post-index period following transition from blood glucose monitoring to CGM. A pre-specified subgroup analysis assessed glucose control and medication changes among people with T2D over 1 year., Results: The analysis included 74 679 adults with T2D (NIT; n = 25 269), (BIT; n = 16 264) and (PIT; n = 33 146). Significant reductions in all-cause hospitalizations, acute diabetes-related hospitalizations and acute diabetes-related emergency room visits were observed in the 6-month post-index period that were sustained during the 6-12 month post-index period (NIT, -10.1%, -31.0%, -30.7%; BIT, -13.9%, -47.6%, -28.2%; and PIT, -22.6%, -52.7%, -36.6%, respectively). A subgroup analysis of 6030 people showed mean glycated haemoglobin reductions at approximately 3 months, which were also sustained throughout the post-index period: NIT, -1.1 (0.05)%; BIT, -1.1 (0.06)%; and PIT, -0.9 (0.04)%, p < 0.0001., Conclusions: CGM use in real-life across different therapeutic regimens in adults with T2D was associated with reductions in health care resource utilization with improved glucose control over 1 year., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.) more...

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway that functions in nutrient recycling and as a mechanism of innate immunity. Previously, we reported a novel host-bacteria interaction between cariogenic S. mutans and bitter taste receptor (T2R14) in gingival epithelial cells (GECs), leading to an innate immune response. Further, S. mutans might be using the host immune system to inhibit other Gram-positive bacteria, such as S. aureus . To determine whether these bacteria exploit the autophagic machinery of GEC, it is first necessary to evaluate the role of T2R14 in modulating autophagic flux. So far, the role of T2R14 in the regulation of autophagy is not well characterized. Therefore, in this study, for the first time, we report that T2R14 downregulates autophagy flux in GECs, and T2R14 knockout increases acidic vacuoles. However, the treatments of GEC WT with a T2R14 agonist and antagonist did not lead to a significant change in acidic vacuole formation. Transmission electron microscopy morphometric results also suggested an increased number of autophagic vesicles in T2R14-knockout GEC. Further, our results suggest that S. mutans competence stimulating peptide CSP-1 showed robust intracellular calcium release and this effect is both T2R14- and autophagy protein 7-dependent. In this study, we provide the first evidence that T2R14 modulates autophagy flux in GEC. The results of the current study could help in identifying the impact of T2R in regulation of the immuno-microenvironment of GEC and subsequently oral health. more...

Publications describe the relevance of the AT-rich interactive domain-containing protein 1A ( ARID1a ) mutation in gastric adenocarcinoma, which occurs predominantly in the microsatellite instable (MSI)- and Epstein-Barr virus (EBV)-associated subtypes. It is unclear whether potential therapeutic, prognostic or morphologic descriptions are not epiphenomena of MSI (or EBV). Since personalised therapeutics are largely lacking for oesophageal adenocarcinoma (EAC), clinical trials investigating the efficacy of these therapeutics specifically in this subgroup are useful. To the best of our knowledge, this was the first study analysing the relevant tumour subset of microsatellite-stable (MSS) EAC with loss of function of ARID1a. A total of 875 patients with EAC and data from The Cancer Genome Atlas (TCGA) were analysed. Statistical analyses associating previously known molecular characteristics of the present tumour cohort, overall survival, morphological growth patterns and tumour heterogeneity issues were considered. Subsequently, 10% of EAC were ARID1a -deficient, the majority of which were MSS (7.5%). There was no characteristic growth pattern. Approximately 60% of tumours were PD-L1 positive to varying degrees. TP53 mutations occurred together with ARID1a defective EAC in the present cohort and in the TCGA collective. The extent of 7.5% MSS-EAC with ARID1a loss was unaffected by neoadjuvant therapy. ARID1a loss was often detected to be homogeneous (92%). ARID1a loss is not an epiphenomenon of MSI in EAC. The high homogeneity of ARID1a loss tumour clones could be considered an argument for the effectiveness of potential therapeutics. Since the majority of genomic ARID1a alterations result in protein loss, immunohistochemistry is a useful screening technique, especially in the absence of morphological characteristics., Competing Interests: All authors declare that they had no competing interests., (Copyright © 2023, Spandidos Publications.) more...

Recent progress in clinical development of KRAS inhibitors has raised interest in predicting the tumor dependency on frequently mutated RAS-pathway oncogenes. However, even without such activating mutations, RAS proteins represent core components in signal integration of several membrane-bound kinases. This raises the question of applications of specific inhibitors independent from the mutational status. Here, we examined CRISPR/RNAi data from over 700 cancer cell lines and identified a subset of cell lines without KRAS gain-of-function mutations (KRAS wt ) which are dependent on KRAS expression. Combining machine learning-based modeling and whole transcriptome data with prior variable selection through protein-protein interaction network analysis by a diffusion kernel successfully predicted KRAS dependency in the KRAS wt subgroup and in all investigated cancer cell lines. In contrast, modeling by RAS activating events (RAE) or previously published RAS RNA-signatures did not provide reliable results, highlighting the heterogeneous distribution of RAE in KRAS wt cell lines and the importance of methodological references for expression signature modeling. Furthermore, we show that predictors of KRAS wt models contain non-substitutable information signals, indicating a KRAS dependency phenotype in the KRAS wt subgroup. Our data suggest that KRAS dependent cancers harboring KRAS wild type status could be targeted by directed therapeutic approaches. RNA-based machine learning models could help in identifying responsive and non-responsive tumors., (© 2022. The Author(s).) more...

This chapter details the generation of atrial fibrin-based engineered heart tissue (EHT) in standard 24-well format as a 3D model for the human atrium. Compared to 2D cultivation, human-induced pluripotent stem cells (hiPSCs)-derived atrial cardiomyocytes demonstrated a higher degree of maturation in 3D format. Furthermore, we have demonstrated in previous work that the model displayed atrial characteristics in terms of contraction and gene expression patterns, electrophysiology, and pharmacological response. Here, we describe how to embed atrial cardiomyocytes differentiated from hiPSCs in a fibrin hydrogel to form atrial EHT attached to elastic silicone posts, allowing auxotonic contraction. In addition, we describe how force and other contractility parameters can be derived from these beating atrial EHTs by video-optical monitoring. The presented atrial EHT model is suitable to study chamber-specific mechanisms, drug effects and to serve for disease modeling., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.) more...

Introduction: TP53 and KEAP1 are frequently mutated in NSCLC, but their prognostic value is ambiguous, particularly in localized stage tumors., Methods: This retrospective cohort study included a total of 6297 patients with NSCLC who were diagnosed between November 1998 and February 2020. The primary end point was overall survival. Patients were diagnosed in a central pathology laboratory as part of the Network Genomic Medicine collaboration, encompassing more than 300 lung cancer-treating oncology centers in Germany. All patients underwent molecular testing, including targeted next-generation panel sequencing and in situ hybridization., Results: A total of 6297 patients with NSCLC were analyzed. In 1518 surgically treated patients (Union for International Cancer Control [UICC] I-IIIA), truncating TP53 mutations and KEAP1 mutations were independent negative prognostic markers in multivariable analysis (hazard ratio [HR] TP53truncating  = 1.43, 95% confidence interval [CI]: 1.07-1.91, p = 0.015; HR KEAP1mut  = 1.68, 95% CI:1.24-2.26, p = 0.001). Consistently, these mutations were associated with shorter disease-free survival. In 4779 patients with advanced-stage (UICC IIIB-IV) tumors, TP53 mutations did not predict outcome in univariable analysis. In contrast, KEAP1 mutations remained a negative prognostic factor (HR KEAP1mut  = 1.40, 95% CI: 1.23-1.61, p < 0.001) in patients with advanced-stage tumors. Furthermore, those with KEAP1-mutant tumors with co-occurring TP53 missense mutations had longer overall survival than those with KEAP1-mutant tumors with wild-type or truncating TP53 mutations., Conclusions: This study found that TP53 and KEAP1 mutations were prognostic for localized and advanced-stage NSCLC. The increased relative hazard of harboring TP53 or KEAP1 mutations was comparable to an increase in one UICC stage. Our data suggest that molecular stratification on the basis of TP53 and KEAP1 mutation status should be implemented for localized and advanced-stage NSCLC to optimize and modify clinical decision-making., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.) more...

Background: Human engineered heart tissue (EHT) transplantation represents a potential regenerative strategy for patients with heart failure and has been successful in preclinical models. Clinical application requires upscaling, adaptation to good manufacturing practices, and determination of the effective dose., Methods: Cardiomyocytes were differentiated from 3 different human induced pluripotent stem cell lines including one reprogrammed under good manufacturing practice conditions. Protocols for human induced pluripotent stem cell expansion, cardiomyocyte differentiation, and EHT generation were adapted to substances available in good manufacturing practice quality. EHT geometry was modified to generate patches suitable for transplantation in a small-animal model and perspectively humans. Repair efficacy was evaluated at 3 doses in a cryo-injury guinea pig model. Human-scale patches were epicardially transplanted onto healthy hearts in pigs to assess technical feasibility., Results: We created mesh-structured tissue patches for transplantation in guinea pigs (1.5×2.5 cm, 9-15×10 6 cardiomyocytes) and pigs (5×7 cm, 450×10 6 cardiomyocytes). EHT patches coherently beat in culture and developed high force (mean 4.6 mN). Cardiomyocytes matured, aligned along the force lines, and demonstrated advanced sarcomeric structure and action potential characteristics closely resembling human ventricular tissue. EHT patches containing ≈4.5, 8.5, 12×10 6 , or no cells were transplanted 7 days after cryo-injury (n=18-19 per group). EHT transplantation resulted in a dose-dependent remuscularization (graft size: 0%-12% of the scar). Only high-dose patches improved left ventricular function (+8% absolute, +24% relative increase). The grafts showed time-dependent cardiomyocyte proliferation. Although standard EHT patches did not withstand transplantation in pigs, the human-scale patch enabled successful patch transplantation., Conclusions: EHT patch transplantation resulted in a partial remuscularization of the injured heart and improved left ventricular function in a dose-dependent manner in a guinea pig injury model. Human-scale patches were successfully transplanted in pigs in a proof-of-principle study. more...

Coronavirus disease 2019 (COVID-19) has wreaked havoc and distressed economies worldwide. Countries have gone on lockdown of their economies to prevent the spread of the disease. This obviously led to collateral damage in the form of worsening healthcare for non-COVID-related conditions and is playing havoc with the world economy. Herein, we suggest novel strategies to prevent COVID-19 related complications, keeping in view the pathophysiology of the disease., (© 2020 Vishal Sehgal, Amit Kalra, Surender Singh, Brian Ulmer, published by Sciendo.) more...

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have enormous potential for the study of human cardiac disorders. However, their physiological immaturity severely limits their utility as a model system and their adoption for drug discovery. Here, we describe maturation media designed to provide oxidative substrates adapted to the metabolic needs of human iPSC (hiPSC)-CMs. Compared with conventionally cultured hiPSC-CMs, metabolically matured hiPSC-CMs contract with greater force and show an increased reliance on cardiac sodium (Na + ) channels and sarcoplasmic reticulum calcium (Ca 2+ ) cycling. The media enhance the function, long-term survival, and sarcomere structures in engineered heart tissues. Use of the maturation media made it possible to reliably model two genetic cardiac diseases: long QT syndrome type 3 due to a mutation in the cardiac Na + channel SCN5A and dilated cardiomyopathy due to a mutation in the RNA splicing factor RBM20. The maturation media should increase the fidelity of hiPSC-CMs as disease models., Competing Interests: Declaration of Interests The authors declare no competing interests. A patent application related to this work has been submitted., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent an unlimited source of human CMs that could be a standard tool in drug research. However, there is concern whether hiPSC-CMs express all cardiac ion channels at physiological level and whether they might express non-cardiac ion channels. In a control hiPSC line, we found large, "noisy" outward K + currents, when we measured outward potassium currents in isolated hiPSC-CMs. Currents were sensitive to iberiotoxin, the selective blocker of big conductance Ca 2+ -activated K + current (I BK,Ca ). Seven of 16 individual differentiation batches showed a strong initial repolarization in the action potentials (AP) recorded from engineered heart tissue (EHT) followed by very early afterdepolarizations, sometimes even with consecutive oscillations. Iberiotoxin stopped oscillations and normalized AP shape, but had no effect in other EHTs without oscillations or in human left ventricular tissue (LV). Expression levels of the alpha-subunit (K Ca 1.1) of the BK Ca correlated with the presence of oscillations in hiPSC-CMs and was not detectable in LV. Taken together, individual batches of hiPSC-CMs can express sarcolemmal ion channels that are otherwise not found in the human heart, resulting in oscillating afterdepolarizations in the AP. HiPSC-CMs should be screened for expression of non-cardiac ion channels before being applied to drug research. more...

One of the dreaded life-threatening complications of diabetes mellitus (DM) is diabetic ketoacidosis (DKA). American Diabetic Association (ADA) came out with 2018 guidelines on the management of DM and its complications, but these are woefully silent on the clinical conundrums that accompany DKA in elderly patients. In elderly patients, DKA is often complicated by sepsis, atrial fibrillation, polypharmacy, nonketotic hyperosmolar states, atypical clinical presentations, acute kidney injury (AKI), dementia, and noncompliance with medications. Here in we highlight these conundrums that need to be addressed to improve morbidity and mortality in elderly patients., Competing Interests: Conflict of Interest None declared. more...

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with greater resemblance to human heart tissue in comparison to standard technique of 2D monolayer (ML) format. I Na was measured in ML or EHT using the standard patch-clamp technique. I Na density was ~1.8 fold larger in EHT (-18.5 ± 1.9 pA/pF; n = 17) than in ML (-10.3 ± 1.2 pA/pF; n = 23; p < 0.001), approaching densities reported for human CM. Inactivation kinetics, voltage dependency of steady-state inactivation and activation of I Na did not differ between EHT and ML and were similar to previously reported values for human CM. Action potential recordings with sharp microelectrodes showed similar upstroke velocities in EHT (219 ± 15 V/s, n = 13) and human left ventricle tissue (LV, 253 ± 7 V/s, n = 25). EHT showed a greater resemblance to LV in CM morphology and subcellular Na V 1.5 distribution. I Na in hiPSC-CM showed similar biophysical properties as in human CM. The EHT format promotes I Na density and action potential upstroke velocity of hiPSC-CM towards adult values, indicating its usefulness as a model for excitability of human cardiac tissue. more...

Since the advent of the generation of human induced pluripotent stem cells (hiPSCs), numerous protocols have been developed to differentiate hiPSCs into cardiomyocytes and then subsequently assess their ability to recapitulate the properties of adult human cardiomyocytes. However, hiPSC-derived cardiomyocytes (hiPSC-CMs) are often assessed in single-cell assays. A shortcoming of these assays is the limited ability to characterize the physiological parameters of cardiomyocytes, such as contractile force, due to random orientations. This protocol describes the differentiation of cardiomyocytes from hiPSCs, which occurs within 14 d. After casting, cardiomyocytes undergo 3D assembly. This produces fibrin-based engineered heart tissues (EHTs)-in a strip format-that generate force under auxotonic stretch conditions. 10-15 d after casting, the EHTs can be used for contractility measurements. This protocol describes parallel expansion of hiPSCs; standardized generation of defined embryoid bodies, growth factor and small-molecule-based cardiac differentiation; and standardized generation of EHTs. To carry out the protocol, experience in advanced cell culture techniques is required. more...

Goosecoid (Gsc) expression marks the primary embryonic organizer in vertebrates and beyond. While functions have been assigned during later embryogenesis, the role of Gsc in the organizer has remained enigmatic. Using conditional gain-of-function approaches in Xenopus and mouse to maintain Gsc expression in the organizer and along the axial midline, neural tube closure defects (NTDs) arose and dorsal extension was compromised. Both phenotypes represent convergent extension (CE) defects, arising from impaired Wnt/planar cell polarity (PCP) signaling. Dvl2 recruitment to the cell membrane was inhibited by Gsc in Xenopus animal cap assays and key Wnt/PCP factors (RhoA, Vangl2, Prickle, Wnt11) rescued Gsc-mediated NTDs. Re-evaluation of endogenous Gsc functions in MO-mediated gene knockdown frog and knockout mouse embryos unearthed PCP/CE-related phenotypes as well, including cartilage defects in Xenopus and misalignment of inner ear hair cells in mouse. Our results assign a novel function to Gsc as an inhibitor of Wnt/PCP-mediated CE. We propose that in the organizer Gsc represses CE as well: Gsc-expressing prechordal cells, which leave the organizer first, migrate and do not undergo CE like the Gsc-negative notochordal cells, which subsequently emerge from the organizer. In this model, Gsc provides a switch between cell migration and CE, i.e. cell intercalation. more...

Neural crest cells (NCCs) migrate throughout the embryo to differentiate into cell types of all germ layers. Initial directed NCC emigration relies on planar cell polarity (PCP), which through the activity of the small GTPases RhoA and Rac governs the actin-driven formation of polarized cell protrusions. We found that the actin binding protein calponin 2 (Cnn2) was expressed in protrusions at the leading edge of migratory NCCs in chicks and frogs. Cnn2 knockdown resulted in NCC migration defects in frogs and chicks and randomized outgrowth of cell protrusions in NCC explants. Morphant cells showed central stress fibers at the expense of the peripheral actin network. Cnn2 acted downstream of Wnt/PCP, as migration defects induced by dominant-negative Wnt11 or inhibition of RhoA function were rescued by Cnn2 knockdown. These results suggest that Cnn2 modulates actin dynamics during NCC migration as an effector of noncanonical Wnt/PCP signaling., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.) more...

Antithyroid medications are the preferred therapy for the treatment of Graves' disease during pregnancy. Propylthiouracil (PTU) is favored over methimazole (MMI) due to potential teratogenic concerns with MMI. This study was to determine the teratogenic potential of MMI and PTU using a validated Xenopus tropicalis embryo model. Embryos were exposed to 1 mM PTU (EC(50)=0.88 mM), 1 mM MMI, or vehicle control (water) from stages 2 to 45. Treated embryos were examined for gross morphological defects, ciliary function, and gene expression by in situ hybridization. Exposure to PTU, but not MMI, led to cardiac and gut looping defects and shortening along the anterior-posterior axis. PTU exposure during gastrulation (stage 8-12.5) was identified as the critical period of exposure leading to left-right (LR) patterning defects. Abnormal cilia polarization, abnormal cilia-driven leftward flow at the gastrocoel roof plate (GRP), and aberrant expression of both Coco and Pitx2c were associated with abnormal LR symmetry observed following PTU exposure. PTU is teratogenic during late blastula, gastrulation, and neurulation; whereas MMI is not. PTU alters ciliary-driven flow and disrupts the normal genetic program involved in LR axis determination. These studies have important implications for women taking PTU during early pregnancy. more...

The mouse transcription factor Noto is expressed in the node and controls node morphogenesis, formation of nodal cilia and left-right asymmetry. Noto acts upstream of Foxj1, which regulates ciliogenesis in other mouse tissues. However, the significance of Foxj1 for the formation of cilia in the mouse node is unclear; in non-amniote species Foxj1 is required for ciliogenesis in the structures equivalent to the node. Here, we analyzed nodes, nodal cilia and nodal flow in mouse embryos in which we replaced the Noto-coding sequence with that of Foxj1, or in embryos that were deficient for Foxj1. We show that Foxj1 expressed from the Noto locus is functional and restores the formation of structurally normal motile cilia in the absence of Noto. However, Foxj1 is not sufficient for the correct positioning of cilia on the cell surface within the plane of the nodal epithelium, and cannot restore normal node morphology. We also show that Foxj1 is essential for ciliogenesis upstream of Rfx3 in the node. Thus, the function of Foxj1 in vertebrate organs of asymmetry is conserved, and Noto regulates node morphogenesis and the posterior localization of cilia on node cells independently of Foxj1. more...

In vertebrates, most inner organs are asymmetrically arranged with respect to the main body axis [1]. Symmetry breakage in fish, amphibian, and mammalian embryos depends on cilia-driven leftward flow of extracellular fluid during neurulation [2-5]. Flow induces the asymmetric nodal cascade that governs asymmetric organ morphogenesis and placement [1, 6, 7]. In the frog Xenopus, an alternative laterality-generating mechanism involving asymmetric localization of serotonin at the 32-cell stage has been proposed [8]. However, no functional linkage between this early localization and flow at neurula stage has emerged. Here, we report that serotonin signaling is required for specification of the superficial mesoderm (SM), which gives rise to the ciliated gastrocoel roof plate (GRP) where flow occurs [5, 9]. Flow and asymmetry were lost in embryos in which serotonin signaling was downregulated. Serotonin, which we found uniformly distributed along the main body axes in the early embryo, was required for Wnt signaling, which provides the instructive signal to specify the GRP. Importantly, serotonin was required for Wnt-induced double-axis formation as well. Our data confirm flow as primary mechanism of symmetry breakage and suggest a general role of serotonin as competence factor for Wnt signaling during axis formation in Xenopus., (Copyright © 2012 Elsevier Ltd. All rights reserved.) more...

A field study in an automotive supply industry company was conducted to explore age-differentiated strain of assembly line workers. Subjective and objective data from 23 female workers aged between 27 and 57 years were collected at the workplace belt buckle assembly during morning shifts. Subjects with medication or chronic diseases affecting heart rate and breath rate were excluded. For subjective data generation different questionnaires were used. Before the Work Ability Index and the Munich Chronotype Questionnaire were completed by the subjects. Short questionnaires (strain-ratings, NASA-TLX) directly at begin and end of the work were used for obtaining shift-related data. During the whole shift (6 a.m. - 2.45 p.m.) bodily functions were logged with a wireless chest strap. In addition, the motion of the hand-arm-system was recorded for 30 times, 3 minutes each after a fixed time-schedule. First results show that younger subjects need significant less time for assembly (mean = 14.940 s) compared to older subjects (mean = 17.040 s; t(472.026) = -9.278 , p < 0.01). more...

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition. more...

Background: Blunt chest trauma represents one of the most common injuries in polytrauma patients. Blunt chest injury complicating polytrauma is associated with significant prolongation of intensive care stay. Further, it has a great impact on the timing of fixation of skeletal injuries, possibly contributing to adverse outcome. The purpose of this study is to assess whether there are any differences in the management and outcome of polytrauma patients with blunt chest trauma between trauma units in two different countries. Detailed information about advantages and disadvantages of these two systems might allow optimising the management of blunt chest trauma., Patients and Methods: This investigation was performed using the polytrauma database of the German Trauma Society and the British Trauma Audit Research Network. After the definition of the inclusion abbreviated injury scale (AIS(chest) > or = 3) and injury severity score (ISS > 16) and exclusion (AIS(head/neck) > or = 2, referral from outside institutions) criteria, patients were recruited solely from these databases., Results: 188 patients from the German database and 181 patients from the British database were enrolled in this study. Demographic data and injury pattern of the two patient populations did not significantly differ. The volume of initial red blood cell transfusion and length of the intensive care stay were significantly higher in Germany (p < 0.05). Mortality in the UK was 9% higher than in Germany (p = 0.057). Time to death in non-survivors was also significantly longer in Germany (p < 0.05)., Conclusions: The reasons for the differences regarding survival times and survival rates seem to be multiple. German patients received more red blood cells, had a longer hospital stay in intensive care and a better survival rate. The use of kinetic therapy in Germany, not standard in the UK, may contribute to a more favourable outcome. more...

Patients with valvular myxoma are usually candidates for surgery because of the high incidence of life-threatening embolism. In some cases, the tumor is sessile or presents with a large peduncle: complete excision may then lead to valve replacement. We report two cases of atrioventricular valve myxoma where replacement was avoided. In one patient, a mitral myxoma appended from the edge of the anterior leaflet close to the chordae insertion; safe excision implied destruction of the two chordae and a peritumoral section of the anterior leaflet. A chordal transposition technique was used to preserve valve competence. In a second patient, a tricuspid myxoma causing syncopal episodes was resected; this was characterized by a large stalk, located on the anterior tricuspid leaflet away from chordal attachment and the valvular annulus. Treatment was by resection and the leaflet reconstructed with a pericardial patch. Techniques for conservative treatment of degenerative valvular disease or endocarditis, when monitored peroperatively by transesophageal echocardiography, may be successful in the surgical resection of atrioventricular myxoma. more...

Breast cancer is the most common cancer in women and is the second (after lung cancer) leading cause of cancer deaths in women. Knowledge of breast cancer and its epidemlology, natural course, and response to treatment continue to evolve, making the survival rates for patients with breast cancer more optimistic. Women with breast cancer must decide, in partnership with expert physicians and nurses, what their options are for screening, diagnosis, and treatment. This article provides an overview of options available to women diagnosed with breast cancer. more...

Isolated internal iliac aneurysms are rare, and although most are of atherosclerotic origin the cause may also be congenital, traumatic, associated with pregnancy or infectious. A 56-year-old man presented with a swollen, painful left lower limb. Within a few days, weakness of the limb developed with fever and an acute abdomen with free air on x-ray. At emergency laparotomy a small perforation was found in the ascending colon. Examination of the left iliac fossa revealed a ruptured left internal iliac artery aneurysm. Extra-anatomic cross-femoral bypass grafting was done to revascularize the left lower extremity. The patient recovered without complication. At discharge the weakness had improved but knee flexion and extension were weak. Culture of the aneurysm contents grew Staphylococcus aureus and Pseudomonas aeruginosa. The authors discuss the presentation and management of infected internal iliac artery aneurysms. more...

A case of therapeutic overdosage in a 58-year-old woman is reported. Lithium plasma level was 3.7 mmol.l. All clinical and biological disturbances regressed in 3 days after controlled rehydration only. Aetiology, clinical picture, biological characteristics and treatment according to the severity of the lithium poisoning are discussed. more...

A 25-year-old man experienced rapidly progressing Budd-Chiari syndrome. Despite extensive radiological investigations, no atrial mass could be identified. At operation, a right atrial myxoma was found that originated from the eustachian valve and prolapsed into the inferior vena cava. Following successful removal of the myxoma, the ascites and peripheral edema resolved completely. Right atrial myxoma is a rare cardiac tumor that may present with embolic, obstructive, or constitutional signs and symptoms and is a potentially curable cause of Budd-Chiari syndrome. more...

Arthroplasties of the hips in dogs using a biodegradable poly-L-lactide cup to protect the regenerating cartilage following removal of normal articular cartilage and the drilling of multiple full thickness defects into subchondral bone were performed to determine whether or not the repair response could be improved. The poly-L-lactide cup degraded in approximately 60 days. The regenerating cartilage was much better in the experimental than the control dogs initially, but ultimately failed, perhaps due to inadequate duration of protection of the immature cartilage by the arthroplasty material. more...

Seven infants aged 6 days to 9 months were tested for the use by rubbing of a pomade containing 1 mg trinitrine. The study was interrupted because of high blood passage of trinitrine. The authors emphasize the difficulty of any comparison with the use of this drug in adults. They indicate that there was no clinically appreciable side-effect but they advise to delay, until further studies, the use of this technique, with the only objective of improving the technique of intravenous injections or sampling. more...

Microcystic cystadenoma of the pancreas is a well-recognized although rare pathological entity. All previously reported examples of this tumor have been uniformly benign in behavior. In this case report, we present a primary tumor of the pancreas that was histologically indistinguishable from microcystic adenoma, but which behaved in a malignant fashion. Metastases were found in the stomach and liver. We believe that this case represents a new entity, which we have termed "serous cystadenocarcinoma of the pancreas." more...