Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

Optimized Continuous Application of Hyperpolarized Xenon to Liquids.

In recent years, NMR with hyperpolarized (HP) xenon inside functionalized host structures (e.g., cryptophanes) have become a potential candidate for the direct observation of metabolic processes (i.e., molecular imaging). A critical issue for real applications is the dissolution of the HP-gas in the liquid which contains the host. In this work, we present recent developments for an improved and controlled dissolution of HP-Xe in liquids using hollow fiber membranes and different compressor systems. The designed apparatus consists of a compressor and a membrane unit. The compressor provides HP-129Xe continuously at small adjustable pressures and in a polarization-preserving way. The membrane unit enables a molecular solution of the HP-gas in aqueous liquids, avoiding the formation of bubbles or even foams. Two different types of compressors were tested in terms of function and useful materials. Special emphasis was put on a systematic reduction of transfer losses in the gas and liquid phase. In order to optimize the system parameters, several physical models were developed to describe the transport and the losses of nuclear polarization. Finally, the successful implementation was demonstrated in several experiments. HP-Xe was dissolved in an aqueous cryptophane-A-(OCH2COOH)6 solution, and stable Xe signals could be measured over 35 min, only limited by the size of the gas reservoir. Such long and stable experimental conditions enabled the study of chemical exchange of xenon between cryptophane and water environments even for a time-consuming 2D NMR experiment. The good signal stability over the measurement time allowed an exact determination of the residence time of the Xe atom inside the cryptophane, resulting in an average residence time of 44.5 ± 2.7 ms.

How to Reach a Thousand-Second in-Plane Polarization Lifetime with 0.97-GeV/c Deuterons in a Storage Ring.

We observe a deuteron beam polarization lifetime near 1000 s in the horizontal plane of a magnetic storage ring (COSY). This long spin coherence time is maintained through a combination of beam bunching, electron cooling, sextupole field corrections, and the suppression of collective effects through beam current limits. This record lifetime is required for a storage ring search for an intrinsic electric dipole moment on the deuteron at a statistical sensitivity level approaching 10^{-29} e cm.

Is pelvic organ support different between young nulliparous African and Caucasian women?

OBJECTIVE: There seems to be substantial variation in the prevalence of pelvic floor disorders between different ethnic groups. This may be due partially to differences in pelvic floor structure and functional anatomy. To date, data on this issue are sparse. The aim of this study was to compare hiatal dimensions, pelvic organ descent and levator biometry in young, healthy nulliparous Caucasian and African women. METHODS: Healthy nulliparous non-pregnant volunteers attending a local nursing school in Uganda were invited to participate in this study during two fistula camps. All volunteers underwent a simple physician-administered questionnaire and a four-dimensional translabial ultrasound examination. Offline analysis was performed to assess hiatal dimensions, pelvic organ descent, levator muscle thickness and area. To compare findings with those obtained in nulliparous non-pregnant Caucasians, we retrieved the three-dimensional/four-dimensional ultrasound volume datasets of a previously published study. RESULTS: The dataset of 76 Ugandan and 49 Caucasian women was analyzed. The two groups were not matched but they were comparable in age and body mass index. All measurements of hiatal dimensions and pelvic organ descent were significantly higher among the Ugandans (all P ≤ 0.01); however, muscle thickness and area were not significantly different between the two groups. CONCLUSIONS: Substantial differences between Caucasian and Ugandan non-pregnant nulliparae were identified in this study comparing functional pelvic floor anatomy. It appears likely that these differences in functional anatomy are at least partly genetic in nature. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

New Method for a Continuous Determination of the Spin Tune in Storage Rings and Implications for Precision Experiments.

A new method to determine the spin tune is described and tested. In an ideal planar magnetic ring, the spin tune-defined as the number of spin precessions per turn-is given by ν(s)=γG (γ is the Lorentz factor, G the gyromagnetic anomaly). At 970 MeV/c, the deuteron spins coherently precess at a frequency of ≈120 kHz in the Cooler Synchrotron COSY. The spin tune is deduced from the up-down asymmetry of deuteron-carbon scattering. In a time interval of 2.6 s, the spin tune was determined with a precision of the order 10^{-8}, and to 1×10^{-10} for a continuous 100 s accelerator cycle. This renders the presented method a new precision tool for accelerator physics; controlling the spin motion of particles to high precision is mandatory, in particular, for the measurement of electric dipole moments of charged particles in a storage ring.

[Alterations of vertebrocerebral arterial branches in children and adolescents - current aspects of epidemiology, diagnostics, treatment, outcome and follow-up including a representative case report]. / Alterationen hirnversorgender Arterien bei Kindern und Jugendlichen - aktuelle Aspekte von Epidemiologie, Diagnostik, Therapie, Outcome und Nachsorge inkl. repräsentativem Fallbericht.

INTRODUCTION: Vascular alterations such as arterial lesions themselves or caused by injuries (external site) occur only rarely in children and adolescents. By means of a narrative review including our own clinical experience and a representative case report, vascular alterations in children and adolescents are discussed. Complex Patient- & clinical Finding-associated Aspects: - Dissections of vertebrocerebral arterial branches: usually, the aetiopathogenesis reveals external factors or primary alterations of the vascular wall. The therapeutic approach comprises anticoagulation or surgical, sometimes endovascular intervention in cases of recurrent ischaemic symptoms. - Aneurysm of the carotid artery: the therapeutic approach is characterised by surgical and interventional treatment according to the individual case-specific finding, alternatives in vascular reconstruction can be derived from the classification by de Jong et al. Representative Case Report: An 11 year old boy was diagnosed with intracranial dissection of the left vertebral artery initially treated with anticoagulation (6 months) and a consecutive neurosurgical approach (trepanation and coverage of the dissecting aneurysm) and, subsequently (within the 16th year of age), he underwent interventional treatment (coil embolisation) because of an expansion of the aneurysm. In addition, an aneurysm of the right internal carotid artery was found, which was approached surgically with interposition of a vena-saphena-magna segment. CONCLUSION: Vascular alterations such as dissections and aneurysms of vertebrocerebral arterial branches in children and adolescents are challenging. Dissections should be treated with anticoagulation. In the case of recurrent ischaemic symptoms or in cases of pressure phenomenon including neurological alterations, interventional or surgical treatment is indicated. In the case of an aneurysm of the carotid artery, there is an indication for surgical treatment: In children and teenagers, venous segments for interposition and single-stitch sutures are usually used. Competent decision-making for treatment and periinterventional management require appropriate interdisciplinary expertise.

[Acute scrotum in childhood]. / Akutes Skrotum im Kindesalter.

BACKGROUND: Due to the variety of differential diagnoses causing acute scrotum and their possible consequences, this finding is a challenge for diagnostic and therapeutic management in the daily clinical practice of paediatric medicine. PATIENTS AND METHODS: Through a defined time period, all consecutive paediatric patients of a tertiary surgical centre aged up to 16 years who were diagnosed with and treated for primary acute scrotum were prospectively registered and retrospectively evaluated for patient, finding and treatment (intervention) associated specifics in this systematic unicentric observational study (design: case series) to reflect daily clinical practice. RESULTS: A total of 141 cases with acute scrotum were enrolled in the study during the 10-year period from January 2000 to December 2009. Eight percent of cases (n = 11) showed bilateral findings. There were two age peaks: newborns and puberty. The most common diagnoses were epididymitis and orchitis (26 %), torsion of the testicular appendix (22 %) and testicular torsion (21 %). Trauma, hydrocele, inguinal hernia, idiopathic scrotal oedema and tumours were rather rare differential diagnoses as possible causes for an acute scrotum. The mean period of discomfort, complaints and symptoms up to presenting in the outpatient clinic was 24 hours. For sixty percent (n = 84, i.e., all patients treated conservatively and 43 % of the operated patients) an imaging study was obtained with ultrasound or Doppler ultrasonography, respectively. Two thirds of the patients underwent an operative exploration. The orchiectomy rate in testicular torsion amounted to 40 %. In one newborn, a bilateral orchiectomy was necessary. In patients with unilateral orchiectomy, a prophylactic fixation of the contralateral testis was performed preferentially at 4-8 weeks after the initial intervention even though a simultaneous procedure is being increasingly used. CONCLUSIONS: In approximately one fifth of registered patients, a testicular torsion is present causing the acute scrotum, and leading to an obligatory surgical intervention. Various causative differential diagnoses can be clarified by precise medical history and exact physical examination. Imaging procedures can be helpful in decision-finding. Finally, the clinical finding is crucial and decisive. If a testicular torsion cannot reliably be excluded by clinical investigation or imaging, an immediate surgical exploration of the testis has to be performed.

[Trauma-associated vascular injuries and the vascular surgical/interventional options for vascular reconstruction]. / Traumaassoziierte Gefäßverletzungen und deren gefäßchirurgische/interventionelle Rekonstruktionsmöglichkeiten.

AIM: The aim of this work is to illustrate the diversity of vascular injuries in terms of vascular segments or body regions, accident mechanisms and specific patient constellations. METHOD: A representative case collection was compiled based on current and relevant scientific references in PubMed, own clinical experiences, vascular surgical and novel image-guided interventional options. RESULTS: The diagnostics of vascular injuries in the context of trauma and fractures are based on a thorough physical examination. In addition, the hard and soft signs preferred by the Western Trauma Association should be included in the decision. Doppler ultrasonography examination is the safest and gentlest noninvasive examination procedure for a suspected vascular injury due to repeatable and comparative measurements. The stabilization of a fracture, ideally using an external fixator, should be performed before vascular reconstruction whenever possible, unless massive bleeding, hypovolemic shock or a rapidly spreading hematoma represent an immediate indication for surgery. In pediatric supracondylar fractures, avascular injury without relevant ischemia has frequently been described (pink pulseless hand). In this case, the fracture should first be reduced as the pulse often recovers. Due to the increasing availability, good technical handling and high technical success rate as well as the relatively limited interventional trauma, endovascular treatment of traumatic vascular injuries has become widely accepted. Traumatic aortic ruptures are associated with a high mortality even at the accident site. Rapid endovascular treatment using a stent prosthesis significantly increases the injured person's chances of survival. CONCLUSION: Vascular injuries in connection with fractures or multiple injuries require interdisciplinary cooperation between the specialties involved.

Is levator avulsion a predictor of cystocele recurrence following anterior vaginal mesh placement?

OBJECTIVE: Levator avulsion has been shown to be a predictor of cystocele recurrence following anterior colporrhaphy. The aim of this study was to determine if levator avulsion is a risk factor for prolapse recurrence following anterior colporrhaphy with mesh. METHODS: This was a retrospective analysis of data obtained from three surgical audits for subjective and objective outcomes following anterior colporrhaphy with mesh. Recurrence was defined as cystocele ≥ Stage 2 on the prolapse quantification system of the International Continence Society; symptoms of vaginal lump/bulge; or cystocele on ultrasound, defined as maximum bladder descent to ≥ 10 mm below the symphysis pubis. Levator avulsion was diagnosed using tomographic ultrasound imaging. RESULTS: Two hundred and nine patients were followed up at a mean of 2.2 years (range, 3 months to 5.6 years) after anterior vaginal mesh placement. 24% (51/209) had recurrent prolapse symptoms, 33% (68/209) clinical cystocele recurrence ≥ Stage 2, and 26% (54/209) a recurrent cystocele on ultrasound. Twenty-eight out of 80 (35%) women with levator avulsion had significant sonographic cystocele recurrence (odds ratio (OR), 2.24 (95% confidence interval (CI), 1.13-4.43)). This finding was confirmed after adjusting for potential predictors of prolapse recurrence on multivariate logistic regression (OR, 2.13 (95% CI, 1.04-4.39); P = 0.04). CONCLUSION: Levator avulsion doubles the risk of cystocele recurrence after anterior colporrhaphy with transobturator mesh.

Anterior compartment mesh: a descriptive study of mesh anchoring failure.

OBJECTIVES: To define types of support failure after anterior compartment mesh placement and to investigate any association with predictors of recurrence. METHODS: This was a retrospective study on patients ≥ 3 months after anterior mesh placement. All patients underwent a standardized interview, clinical examination using the International Continence Society Pelvic Organ Prolapse Quantification system (ICS POP-Q) and three-dimensional/four-dimensional (3D/4D) translabial ultrasound. Mesh failure was defined as recurrence of anterior/central compartment prolapse seen on ultrasound. Failures were classified as anterior, global and apical. Their association with hiatal area on Valsalva maneuver and levator avulsion was tested. RESULTS: Three hundred and one patients were seen initially, of whom five were excluded because of missing data, leaving 296. Mean follow-up was 1.8 (range, 0.3-5.6) years. Mean age was 65 (range, 32-88) years. One hundred and thirty-nine (47%) women were fitted with a Perigee mesh, 66 (22%) with an Anterior Prolift mesh and 91 (31%) with an Anterior Elevate mesh. Recurrent symptoms (lump/drag) were reported in 65 (22%), a recurrent cystocele was noted in 128 clinically (43%) and in 105 on ultrasound (35%). Avulsion was diagnosed in 117 patients (40%). Mean hiatal area on Valsalva was 33.3 (range, 14.1-60.0) cm2. Mesh failure was diagnosed in 112 patients (38%), comprising global failure in 81 (27%), apical failure in 23 (8%) and anterior failure in eight (3%). Apical and global failures were significantly associated with hiatal area, associations that remained after controlling for potential confounders. CONCLUSIONS: Mesh failure, i.e. anterior or central compartment recurrent prolapse, was noted in 38% of patients on average 1.8 years after placement of anterior compartment mesh. Global and apical failures together constituted 93% of all mesh failures, both types of failure being significantly associated with hiatal area on Valsalva maneuver.

[Age-dependent visceral medicine: paediatric visceral medicine - visceral medical paediatrics - considerations on the short bowel syndrome in childhood]. / Altersabhängige Viszeralmedizin: pädiatrische Viszeralmedizin - viszeralmedizinische Pädiatrie - Überlegungen zum Kurzdarmsyndrom im Kindesalter.

There are several reasons for the possible development of a short bowel syndrome, which, however, occurs only rarely. The main causes consist of extended intestinal resections in cases of congenital anomalies (e.g., gastroschisis, intestinal atresia or dysplasia) or ischaemic lesions due to a volvulus. In addition, an intestinal stoma at a more upper segment of the GI tract can result in the functional manifestation of a short bowel syndrome. The differentiation between temporary and persisting types is essential for initiation of an adequate treatment. Loss or exclusion of organic resorption area at the inner surface of the (small) intestine can be associated with numerous pathological consequences requiring treatment. As a principle consideration from the paediatric point of view, the potential of intestinal adaptation needs to be assessed. Basic conservative treatment options are parenteral and enteral nutrition regimens, in particular, to prevent complications (such as D-lactate acidosis). The main surgical approaches are the procedures called LILT (longitudinal intestinal lengthening and tailoring) according to Bianchi and STEP (serial transverse enteroplasty). The technique to create intestinal segments of antiperistalsis has been abandoned. Because of the encouraging results of intestinal transplantation, this novel treatment option has gained greater attention over the past few years and is now also an option for paediatric patients. The limiting factor and thus major complication is the central venous catheter for long-term treatment. Catheter-related complications are still the main reason for a considerable mortality in these children.

Evaluation of functional MR-urography in complex obstructive uropathy of infants: comparison to the conventional diagnostic algorithm--a pilot study.

OBJECTIVES: To analyze the impact of functional magnetic resonance urography (fMRU) on the therapeutic management in infants with complex obstructive uropathy (OU) compared to the conventional diagnostic algorithm [CDA, ultrasound, radioisotope nephrography (RN)]. METHODS: Retrospective analysis on 10 consecutive infants [female, n=3; male, n=7; age, 10.7 (2-17) months] with OU. Patients were examined according to CDA. If CDA revealed inconclusive results, fMRU was performed additionally. Split kidney function was assessed by RN [single kidney function (SKF)] and fMRU [volumetric differential renal function (vDRF)]. Findings were presented to an interdisciplinary truth-panel in a 2-step decision process (with and without fMRU). Clinical decision was determined. RESULTS: CDA indicated surgical intervention in 8 patients and conservative treatment in 2. Information by fMRU changed treatment strategy in 3 patients and led to the modification of the initially chosen surgical approach in 8 cases. The comparison of SKF and vDRF was not possible in 1 patient, whereas concordance was observed in 7 patients. SKF and vDRF differed >5% in 2 patients. CONCLUSIONS: fMRU has potential to improve therapeutic management of OU in infants. If surgical treatment is advised, the morphological information by fMRU has to be emphasized. Regarding kidney function estimation preliminary results are encouraging.

[Therapeutic options for haemangiomas of infancy]. / Überblick der Therapiemöglichkeiten im Management von Säuglingshämangiomen.

The necessity of haemangioma treatment in infants has been controversially discussed for years. One reason is the favoured clinical observation of a potential spontaneous involution without any therapeutic approach or medical treatment, thus avoiding their specific risks. On the other hand, there are several reports on serious cases with -rapidly growing haemangiomas including severe consequences. There are potential complications such as loss of visus in cases of periorbital manifestation. A basic problem is the lack of a unique systematic classification, on the basis of which -diagnostic measures, therapeutic indications and modes could be compared. Such a classification would be much more competent including a sufficient comparison of treatment results. The basic aim in management is to achieve control of the haemangioma growth and induction of its sub-sequent involution back to only a cosmetic detraction. Each threatening functional loss can be classified as an urgent indication for treatment. There is a need to consider the treatment options and their values; in particular, cryotherapy or laser therapy in localised manifestations are mostly -favoured because of the convincing evidence from available data. In the case of a more disseminated haemangioma manifestation, the initiation of propranol medication is possible, a novel drug for this indication. However, there are no follow-up data on the mid-term or long-term outcome available at this time. Further studies on the subject are therefore required.

[Complication rate after femoral shaft fractures in childhood and adolescence depending on patient factors and treatment measures]. / Die Komplikationsrate nach Femurschaftfrakturen im Kindes- und Jugendalter in Abhängigkeit von Patientenfaktoren und Behandlungsmaßnahmen.

BACKGROUND: The treatment of pediatric femoral shaft fractures has undergone an increasing change in recent years. The previously predominant treatment procedures were extensively replaced by minimally invasive techniques (e.g. elastic stable intramedullary nailing, ESIN). The aim of this study was the comparison of complication rates depending on patient factors as well as various treatment procedures. MATERIAL AND METHODS: This study involved a retrospective X­ray morphometric evaluation of data. The patient files and X­rays of 101 children who were treated at 2 level I trauma centers were analyzed. RESULTS: Conservative treatment was carried out in 19% of the cases. Among the surgical procedures the ESIN technique was predominant (n = 60). Complications that needed revision occurred in 10% of the children after conservative treatment. Revision surgery had to be carried out in more than 6% of the cases in children who were surgically treated. Among the surgical procedures ESIN stabilization demonstrated the lowest revision rate with only 3%. Children under three years and adolescents had a higher risk for developing complications. If the ESIN wires used were too thin in relation to the diameter of the medullary cavity there was an increased probability of complications of around 30%. CONCLUSION: This study revealed a moderate risk of complications in the treatment of femoral shaft fractures in children. The risk of complications after external fixation and conservative treatment was the highest in this study. Overall, the ESIN technique showed the lowest risk of complications. The results of this study could confirm the known limitations of the ESIN technique depending on age and body weight.

ECM-transmitted shear stress induces apoptotic cell extrusion in early breast gland development.

Epithelial cells of human breast glands are exposed to various mechanical ECM stresses that regulate tissue development and homeostasis. Mechanoadaptation of breast gland tissue to ECM-transmitted shear stress remained poorly investigated due to the lack of valid experimental approaches. Therefore, we created a magnetic shear strain device that enabled, for the first time, to analyze the instant shear strain response of human breast gland cells. MCF10A-derived breast acini with basement membranes (BM) of defined maturation state and basoapical polarization were used to resemble breast gland morphogenesis in vitro. The novel biophysical tool was used to apply cyclic shear strain with defined amplitudes (≤15%, 0.2 Hz) over 22 h on living spheroids embedded in an ultrasoft matrix (<60 Pa). We demonstrated that breast spheroids gain resistance to shear strain, which increased with BM maturation and basoapical polarization. Most intriguingly, poorly developed spheroids were prone to cyclic strain-induced extrusion of apoptotic cells from the spheroid body. In contrast, matured spheroids were insensitive to this mechanoresponse-indicating changing mechanosensing or mechanotransduction mechanisms during breast tissue morphogenesis. Together, we introduced a versatile tool to study cyclic shear stress responses of 3D cell culture models. It can be used to strain, in principle, all kinds of cell clusters, even those that grow only in ultrasoft hydrogels. We believe that this approach opens new doors to gain new insights into dynamic shear strain-induced mechanobiological regulation circuits between cells and their ECM.

Physical degradation of proteins in well-defined fluid flows studied within a four-roll apparatus.

In most applications of biotechnology and downstream processing proteins are exposed to fluid stresses in various flow configurations which often lead to the formation of unwanted protein aggregates. In this paper we present physical degradation experiments for proteins under well-defined flow conditions in a four-roll apparatus. The flow field was characterized numerically by computational fluid dynamics (CFD) and experimentally by particle image velocimetry (PIV). The local shear strain rate as well as the local shear and elongation rate was used to characterize the hydrodynamic stress environment acting on the proteins. Lysozyme was used as a model protein and subjected to well-defined fluid stresses in high and low stress environment. By using in situ turbidity measurements during stressing the aggregate formation was monitored directly in the fluid flow. An increase in absorbance at 350 nm was attributed to a higher content of visible particles (>1 µm). In addition to lysozyme, the formation of aggregates was confirmed for two larger proteins (bovine serum albumin and alcohol dehydrogenase). Thus, the presented experimental setup is a helpful tool to monitor flow-induced protein aggregation with high reproducibility. For instance, screening experiments for formulation development of biopharmaceuticals for fill and finish operations can be performed in the lab-scale in a short time-period if the stress distributions in the application are transferred and applied in the four-roll mill.

Interleukin-15 protects from lethal apoptosis in vivo.

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15-IgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.

[What must the (abdominal) surgeon know about paediatric surgery - paediatric surgical aspects in general (abdominal) surgery]. / Was muss der (Viszeral-)Chirurg von der Kinderchirurgie wissen - kinderchirurgische Aspekte in der (Viszeral-)Chirurgie.

Due to the advances in neonatal intensive care medicine, prenatal ultrasound-guided diagnostic measures and paediatric surgical options, conditions have been established to achieve long-term survival in newborns with severe diseases. In addition, this means that the "non-paediatric" physician can be increasingly confronted with patients who would not have survived childhood some decades ago. Therefore, the article summarises concisely selected diseases of premature infants and newborns, e. g., congenital abdominal wall defects, and outlines possible long-term consequences based on the surgical interventions and their basic diseases, respectively, which need to be adequately cared for in the case of a surgical disease of the former patient of paediatric surgery. The overview cannot be considered as a complete revision course; however, it might constitute a basic outline for thought-provoking impulses for personal professional skills and expertise in managing such patients in later age from a surgical perspective.

Motor impairment in liver cirrhosis without and with minimal hepatic encephalopathy.

AIM: Manifest hepatic encephalopathy (HE) goes along with motor symptoms such as ataxia, mini-asterixis, and asterixis. The relevance of motor impairments in cirrhotics without and with minimal HE (mHE) is still a matter of debate. PATIENTS AND METHODS: We tested three different groups of patients with liver cirrhosis: no signs of HE (HE 0), mHE, and manifest HE grade 1 according to the West Haven criteria (HE 1). All patients (n = 24) and 11 healthy control subjects were neuropsychometrically tested including critical flicker frequency (CFF), a reliable measure for HE. Motor abilities were assessed using Fahn Tremor Scale and International Ataxia Rating Scale. Fastest alternating index finger movements were analyzed for frequency and amplitude. RESULTS: Statistical analyses showed an effect of HE grade on tremor and ataxia (P < 0.01). Additionally, both ratings yielded strong negative correlation with CFF (P < 0.01, R = -0.5). Analysis of finger movements revealed an effect of HE grade on movement frequency (P < 0.03). Moreover, decreasing movement frequency and increasing movement amplitude parallel decreasing CFF (P < 0.01, R = 0.6). CONCLUSION: Our results indicate that ataxia, tremor, and slowing of finger movements are early markers for cerebral dysfunction in HE patients even prior to neuropsychometric alterations becoming detectable.

Vaginal repair with mesh versus colporrhaphy for prolapse: a randomised controlled trial.

OBJECTIVE: To compare vaginal repair augmented by mesh with traditional colporrhaphy for the treatment of pelvic organ prolapse. DESIGN: Prospective randomised controlled trial. SETTING: Tertiary teaching hospital. POPULATION: One hundred and thirty-nine women with stage >or=2 prolapse according to the pelvic organ prolapse quantification (POP-Q) system requiring both anterior and posterior compartment repair. METHODS: Subjects were randomised to anterior and posterior vaginal repair with mesh augmentation (mesh group, n = 69) or traditional anterior and posterior colporrhaphy (no mesh group, n = 70). MAIN OUTCOME MEASURES: The primary outcome was the absence of POP-Q stage >or=2 prolapse at 12 months. Secondary outcomes were symptoms, quality-of-life outcomes and satisfaction with surgery. Complications were also reported. RESULTS: For subjects attending the 12-month review, success in the mesh group was 81.0% (51 of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not significantly different (P-value = 0.07). A high level of satisfaction with surgery and improvements in symptoms and quality-of-life data were observed at 12 months compared to baseline in both groups, but there was no significant difference in these outcomes between the two groups. Vaginal mesh exposure occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported by five of 30 (16.7%) sexually active women in the mesh group and five of 33 (15.2%) in the no mesh group at 12 months. CONCLUSION: In this study, vaginal surgery augmented by mesh did not result in significantly less recurrent prolapse than traditional colporrhaphy 12 months following surgery.