Risk factors and outcomes associated with type of uterine rupture.

PURPOSE: To identify risk factors associated with the occurrence of complete uterine rupture (CUR) in comparison to partial uterine rupture (PUR) to further investigate to what extent a standardized definition is needed and what clinical implications can be drawn. METHODS: Between 2005 and 2017 cases with CUR and PUR at Charité University Berlin, Germany were retrospectively identified. Demographic, obstetric and outcome variables were analyzed regarding the type of rupture. Binary multivariate regression analysis was conducted to identify risk factors associated with CUR. In addition, the intended route of delivery (trial of labor after cesarean delivery (TOLAC) and elective repeat cesarean delivery (ERCD)), divided according to the type of rupture, was compared. RESULTS: 92 cases with uterine rupture were identified out of a total of 64.063 births (0.14%). Puerperal complications were more frequent in CUR (67.9 versus 41.1%, p = 0.021). Multiparity ≥ 3 was more frequent in CUR (31 versus 10.7%, p = 0.020). Factors increasing the risk for CUR were parity ≥ 3 (OR = 3.8, p = 0.025), previous vaginal birth (OR = 4.4, p = 0.011), TOLAC (OR = 6.5, p < 0.001) and the use of oxytocin (OR = 2.9, p = 0.036). After multivariate analysis, the only independent risk factor associated with CUR was TOLAC (OR = 7.4, p = 0.017). CONCLUSION: TOLAC is the only independent risk factor for CUR. After optimized antenatal counselling TOLAC and ERCD had comparable short-term maternal and fetal outcomes in a high resource setting. A high number of previous vaginal births does not eliminate the risk of uterine rupture. A clear distinction between CUR and PUR is essential to ensure comparability among studies.

Incidence of incisional hernia after laparoscopic liver resection.

BACKGROUND: Minimally invasive techniques have been broadly introduced to liver surgery during the last couple of years. In this study, we aimed to report the incidence and potential risk factors for incisional hernia (IH) as well as health-related quality of life (HRQoL) after laparoscopic liver resections (LLR). METHODS: All patients undergoing LLR between January 2014 and June 2017 were contacted for an outpatient hernia examination. In all eligible patients, photo documentation of the scar was performed and IH was evaluated by clinical examination and by ultrasound. Patients also completed a questionnaire to evaluate IH-specific symptoms and HRQoL. Obtained results were retrospectively analyzed with regard to patients' characteristics, perioperative outcomes and applied minimally invasive techniques, such as multi-incision laparoscopic liver surgery or hand-assisted/single-incision laparoscopic surgery (HALS/SILS). RESULTS: Of 184 patients undergoing surgery, 161 (87.5%) met the inclusion criteria and 49 patients (26.6%) participated in this study. After a median time of 26 months (range 19-50 months) after surgery, we observed an overall incidence of IH of 12%. Five of 6 patients were overweight or obese (BMI ≥ 25) and 5 of 6 hernias were located at the umbilical site. Univariate analysis suggested the performance status at time of operation (ASA score ≥ 3; HR 5.616, 95% CI 1.012-31.157, p = 0.048) and the approach (HALS/SILS, HR 6.571, 95% CI 1.097-39.379, p = 0.039) as potential risk factors for IH. A higher frequency of hernia-related physical restrictions (HRR; p = 0.058) and a decreased physical functioning (p = 0.17) were noted in patients with IH; however, both being short of statistical significance. CONCLUSION: Advantages of laparoscopic surgery with regard to low rates of IH can be translated to minimally invasive liver surgery. Even though there are low rates of IH, patients with poor performance status at the time of operation should be monitored closely. While patients' characteristics are hard to influence, it might be worth focusing on surgical factors such as the approach and the closure of the umbilical site to further minimize the rate of IH.

A propensity-matched study of full laparoscopic versus hand-assisted minimal-invasive liver surgery.

BACKGROUND AND AIM: The implications of multi-incision (MILS) and hand-assisted (HALS) laparoscopic techniques for minimally invasive liver surgery with regard to perioperative outcomes are not well defined. The purpose of this study was to compare MILS and HALS using propensity score matching. METHODS: 309 patients underwent laparoscopic liver resections (LLR) between January 2013 and June 2018. Perioperative outcomes were analyzed after a 1:1 propensity score match. Subgroup analyses of matched groups, i.e., radical lymphadenectomy (LAD) as well as resections of posterosuperior segments (VII and/or VIII), were performed. RESULTS: MILS was used in 187 (65.2%) and HALS in 100 (34.8%) cases, with a significant decrease of HALS resections over time (p = 0.001). There were no significant differences with regard to age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) Score, previous abdominal surgery and cirrhosis between both groups. Patients scheduled for HALS were characterized by a significantly higher rate of malignant tumors (p < 0.001) and major resections (p < 0.001). After propensity score matching (PMS), 70 cases remained in each group and all preoperative variables as well as resection extend were well balanced. A significantly higher rate of radical LAD (p = 0.039) and posterosuperior resections was found in the HALS group (p = 0.021). No significant differences between the matched groups were observed regarding operation time, conversion rate, frequency of major complications, length of intensive care unit (ICU) stay, overall hospital stay and R1 rate. CONCLUSION: Our analysis suggests MILS and HALS to be equivalent regarding postoperative outcomes. HALS might be particularly helpful to accomplish complex surgical procedures during earlier stages of the learning curve.

[Management of patients with chronic pain in acute and perioperative medicine : An interdisciplinary challenge]. / Management von Patienten mit chronischen Schmerzen in der Akut- und perioperativen Medizin : Eine interdisziplinäre Herausforderung.

Chronic pain is a frequent comorbidity of patients in hospitals and has an influence on the clinical course and the duration of hospitalization. There is a need to have a better understanding of chronic pain as a comorbidity and it should be considered to a greater extent in understanding diseases, in treatment concepts and hospital structures to ensure a resource-oriented and high-quality care. This begins on admission by identifying pre-existing pain and related risk factors with the medical history and taking these into account in the treatment regimen. A multimodal treatment approach that involves medicinal, educational, psychological and physiotherapeutic expertise is required in these patients. A unimodal approach in the treatment is not effective. A pain physician should be involved in the treatment team as early as possible. Furthermore, psychological joint supervision should be available for these patients as several studies have demonstrated positive perioperative effects of psychological approaches on the treatment in this patient group.

Laparoscopic versus open hemihepatectomy-a cost analysis after propensity score matching.

INTRODUCTION: Cost efficiency is important for hospitals in order to provide high-quality health care for all patients. As hemihepatectomies are increasingly being performed laparoscopically, the aims of this study were to evaluate the costs of laparoscopic hemihepatectomy and to compare them to conventional open techniques. PATIENTS AND METHODS: This is a retrospective analysis of clinical outcomes and financial calculations of all patients who underwent hemihepatectomy between January 2015 and December 2016 at the Department of Surgery, Campus Charité Mitte and Campus Charité Virchow-Klinikum, Berlin, Germany, being allocated to the DRG (diagnosis-related group) H01A (complex operations of the liver and pancreas with complex intensive care treatment) or H01B (operations of the liver and pancreas without complex intensive care treatment). To overcome selection bias, a 1:1 propensity score matching (PSM) analysis was performed. RESULTS: After PSM, a total of 64 patients were identified; 32 patients underwent laparoscopic hemihepatectomy (LH); and 32 patients received open hemihepatectomy (OH). After PSM, no significant differences were observed in clinical baseline characteristics. The duration of surgery was significantly longer for patients undergoing LH compared to OH (LH, 334 min, 186-655 min; OH, 274 min, 176-454 min; p = 0.005). Patients in the LH group had a significantly shortened median hospital stay of 5 d, when compared to OH (LH, 9.5 d, 3-35 d; OH, 14.5 d, 7-37d; p = 0.005). We observed a significant higher rate of postoperative complication in the OH group (p = 0.022). Cost analysis showed median overall costs of 17,369.85€ in the LH group and 16,103.64€ in the OH group (p = 0.390). CONCLUSION: Our data suggest that higher intraoperative costs of laparoscopic liver surgery, e.g., for surgical devices and due to longer operation times, are compensated by fewer postoperative complications and consecutive shorter length of stay when compared with OH.

Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence.

Major depressive disorder (MDD) is a complex illness caused by both genetic and environmental factors. Antidepressant resistance also has a genetic component. To date, however, very few genes have been identified for major depression or antidepressant resistance. In this study, we investigated whether outbred heterogeneous stock (HS) rats would be a suitable model to uncover the genetics of depression and its connection to antidepressant resistance. The Wistar Kyoto (WKY) rat, one of the eight founders of the HS, is a recognized animal model of juvenile depression and is resistant to fluoxetine antidepressant treatment. We therefore hypothesized that adolescent HS rats would exhibit variation in both despair-like behavior and response to fluoxetine treatment. We assessed heritability of despair-like behavior and response to sub-acute fluoxetine using a modified forced swim test (FST) in 4-week-old HS rats. We also tested whether blood transcript levels previously identified as depression biomarkers in adolescent human subjects are differentially expressed in HS rats with high vs. low FST immobility. We demonstrate heritability of despair-like behavior in 4-week-old HS rats and show that many HS rats are resistant to fluoxetine treatment. In addition, blood transcript levels of Amfr, Cdr2 and Kiaa1539, genes previously identified in human adolescents with MDD, are differentially expressed between HS rats with high vs. low immobility. These data demonstrate that FST despair-like behavior will be amenable to genetic fine-mapping in adolescent HS rats. The overlap between human and HS blood biomarkers suggest that these studies may translate to depression in humans.

Activation of Akt/FKHR in the medulla oblongata contributes to spontaneous respiratory recovery after incomplete spinal cord injury in adult rats.

After incomplete spinal cord injury (SCI), patients and animals may exhibit some spontaneous functional recovery which can be partly attributed to remodeling of injured neural circuitry. This post-lesion plasticity implies spinal remodeling but increasing evidences suggest that supraspinal structures contribute also to the functional recovery. Here we tested the hypothesis that partial SCI may activate cell-signaling pathway(s) at the supraspinal level and that this molecular response may contribute to spontaneous recovery. With this aim, we used a rat model of partial cervical hemisection which injures the bulbospinal respiratory tract originating from the medulla oblongata of the brainstem but leads to a time-dependent spontaneous functional recovery of the paralyzed hemidiaphragm. We first demonstrate that after SCI the PI3K/Akt signaling pathway is activated in the medulla oblongata of the brainstem, resulting in an inactivation of its pro-apoptotic downstream target, forkhead transcription factor (FKHR/FOXO1A). Retrograde labeling of medullary premotoneurons including respiratory ones which project to phrenic motoneurons reveals an increased FKHR phosphorylation in their cell bodies together with an unchanged cell number. Medulla infusion of the PI3K inhibitor, LY294002, prevents the SCI-induced Akt and FKHR phosphorylations and activates one of its death-promoting downstream targets, Fas ligand. Quantitative EMG analyses of diaphragmatic contractility demonstrate that the inhibition of medulla PI3K/Akt signaling prevents spontaneous respiratory recovery normally observed after partial cervical SCI. Such inhibition does not however affect either baseline contractile frequency or the ventilatory reactivity under acute respiratory challenge. Together, these findings provide novel evidence of supraspinal cellular contribution to the spontaneous respiratory recovery after partial SCI.

A single gene defect causing claustrophobia.

Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia.

Using 2H labeling with neutron radiography for the study of solid polymer electrolyte water transport properties.

A method combining (2)H labeling of different sources of H atoms (hydrogen, water vapor) with neutron imaging for the analysis of transport parameters in the bulk and at the interfaces of Nafion polymer electrolyte membranes is proposed. The use of different isotope compositions in the steady state allows evaluation of the relation between bulk and interface transport parameters, but relies on literature data for evaluating absolute values. By using transients of isotope composition, absolute values of these parameters including the self-diffusion coefficient of H can be extracted, making this method an attractive alternative to self-diffusion measurements using nuclear magnetic resonance (NMR), allowing measurements in precisely controlled conditions in real fuel cell structures. First measurements were realized on samples with and without electrodes and we report values of the self-diffusion coefficient of the same order of magnitude as values measured using NMR, although with slightly higher numbers. In our particular case, lower interfacial exchange rates for water transport were observed for samples with an electrode.

Dissociation of accumulated genetic risk and disease severity in patients with schizophrenia.

Genotype-phenotype correlations of common monogenic diseases revealed that the degree of deviation of mutant genes from wild-type structure and function often predicts disease onset and severity. In complex disorders such as schizophrenia, the overall genetic risk is still often >50% but genotype-phenotype relationships are unclear. Recent genome-wide association studies (GWAS) replicated a risk for several single-nucleotide polymorphisms (SNPs) regarding the endpoint diagnosis of schizophrenia. The biological relevance of these SNPs, however, for phenotypes or severity of schizophrenia has remained obscure. We hypothesized that the GWAS 'top-10' should as single markers, but even more so upon their accumulation, display associations with lead features of schizophrenia, namely positive and negative symptoms, cognitive deficits and neurological signs (including catatonia), and/or with age of onset of the disease prodrome as developmental readout and predictor of disease severity. For testing this hypothesis, we took an approach complementary to GWAS, and performed a phenotype-based genetic association study (PGAS). We utilized the to our knowledge worldwide largest phenotypical database of schizophrenic patients (n>1000), the GRAS (Göttingen Research Association for Schizophrenia) Data Collection. We found that the 'top-10' GWAS-identified risk SNPs neither as single markers nor when explored in the sense of a cumulative genetic risk, have any predictive value for disease onset or severity in the schizophrenic patients, as demonstrated across all core symptoms. We conclude that GWAS does not extract disease genes of general significance in schizophrenia, but may yield, on a hypothesis-free basis, candidate genes relevant for defining disease subgroups.

Adhesion and proliferation of cells on new polymers modified biomaterials.

Up to today, several techniques have been used to maintain cells in culture for studying many aspects of cell biology and physiology. More often, cell culture is dependent on proper anchorage of cells to the growth surface. Poly-l-lysine is commonly used as adhesive molecule. In this study, we present, as an alternative to poly-l-lysine, new polymer film substrates, realized by electropolymerization of different monomers on fluorine-doped tin oxide (FTO) surfaces since electropolymerization is a good method to coat selectively metallic or semiconducting electrodes with polymer films. So, the adhesion, proliferation and morphology of rat neuronal cell lines were investigated on polymer treated surfaces. Several amine-based biocompatible polymers were tested: polyethyleneimine (PEI), polypropyleneimine (PPI), polypyrrole (PPy) and poly(p-phenylenediamine) (PPPD). These polymer films were coated on FTO surfaces by electrochemical oxidation. After 8 h in a culture medium, a high percentage of cells was found to be attached to PEI and PPI compared to the other polymers and to the reference surfaces (glass and FTO uncovered). After 24 and 72 h in the culture medium, cells were found to proliferate faster on PEI and PPI than on other polymers and reference surfaces. Consequently, cells have a greater fold expansion on PEI and PPI than on PPPD, PPy or glass and FTO uncoated. From these results, we deduce that PEI and PPI can be useful as coating surface to cultivate neuronal cells.

Accumulation of Ym1/2 protein in the mouse olfactory epithelium during regeneration and aging.

A unique feature of the olfactory system is its efficiency to produce new neurons in the adult. Thus, destruction of the olfactory receptor neurons (ORNs) using chemical (intranasal perfusion with ZnSO4) or surgical (axotomy or bulbectomy) methods, leads to an enhanced rate of proliferation of their progenitors and to complete ORNs regeneration. The aim of our study was to identify new factors implied in this regenerative process. Using an electrophoretic method, we observed the accumulation of a 42 kDa protein after axotomy in the olfactory mucosa, but not in the olfactory bulb. Its expression started after a few days following injury and increased massively during the phase of ORN regeneration. The purification and the sequence characterization revealed that this protein was Ym1/2, recently identified in activated macrophages present in various tissues during inflammation. Western blotting analysis of Ym1/2 confirmed the accumulation of this protein in the regenerating olfactory mucosa consecutively to olfactory axotomy or bulbectomy but also after ZnSO4 irrigation of the nasal cavity. In the olfactory mucosa of control mice, Ym1/2 was hardly detectable in young animals and became more and more abundant with increasing age. In injured and aged mice, Ym1/2 mainly accumulates in the cytoplasm of supporting cells as well as in other cells located throughout the olfactory epithelium. Our results suggest that Ym1/2 is involved in olfactory epithelium remodeling following several kinds of lesions of the adult olfactory mucosa and support the view of a critical role of inflammatory cues in neurodegeneration and aging.

[Optimized image processing with modified preprocessing of image data sets of a transparent imaging plate by way of the lateral view of the cervical spine]. / Optimierte Bildverarbeitung durch ein modifiziertes Pre-Processing von Bilddatensätzen eines transparenten Speicherfoliensystems am Beispiel der seitlichen HWS-Aufnahme.

PURPOSE: To improve the diagnostic quality of lateral radiographs of the cervical spine by pre-processing the image data sets produced by a transparent imaging plate with both-side reading and to evaluate any possible impact on minimizing the number of additional radiographs and supplementary investigations. MATERIAL AND METHODS: One hundred lateral digital radiographs of the cervical spine were processed with two different methods: processing of each data set using the system-imminent parameters and using the manual mode. The difference between the two types of processing is the level of the latitude value. Hard copies of the processed images were judged by five radiologists and three neurosurgeons. The evaluation applied the image criteria score (ICS) without conventional reference images. RESULTS: In 99 % of the lateral radiographs of the cervical spine, all vertebral bodies could be completed delineated using the manual mode, but only 76 % oft the images processed by the system-imminent parameters showed all vertebral bodies. Thus, the manual mode enabled the evaluation of up to two additional more caudal vertebral bodies. The manual mode processing was significantly better concerning object size and processing artifacts. This optimized image processing and the resultant minimization of supplementary investigations was calculated to correspond to a theoretical dose reduction of about 50 %. CONCLUSION: The introduction of optimized organ programs for the upper and lower cervical spine based on the 12-bit data of the images should improve the evaluation of the lateral radiograph of the cervical spine without reducing the latitude value.

[First clinical experience with a full-size, flat-panel detector for imaging the peripheral skeleton - Part II: Post-processing with a newly developed adaptive autowindow algorithm]. / Erste klinische Erfahrungen mit einem grossformatigen Flächendetektorsystem bei Aufnahmen des peripheren Skelettsystems - Teil 2 : Nachverarbeitung mit einem neu entwickelten adaptiven Autofensteralgorithmus -

PURPOSE: of the second part of the investigation was the evaluation of a newly developed adaptive autowindow algorithm in comparison to the system processing radiographs of the wrist and ankle to further optimize the image quality with softcopy reading. MATERIAL AND METHODS: All 120 radiographs of the wrist and all 100 radiographs of the ankle used in the 1st part of this paper were processed with the adaptive autowindow algorithm. The evaluation was again performed by 5 radiologists with softcopy reading. For the data analysis a variation of the Visual Grading Analysis (VGA) was used. RESULTS: Up to 19 % of the wrist radiographs and 2 % of the ankle radiographs processed with the system software had to be processed manually afterwards to get acceptable results. By the application of the adaptive autowindow algorithm a manual post-processing was no longer necessary. Highly significant (p less-than-or-equal 0.001) differences for all criteria to be evaluated were found for the wrist radiographs and in the case of the ankle radiographs for the bone contrast, the contrast in soft-tissue regions, the fine details in the bone and the artifacts, the adaptive autowindow algorithm performed always better than the system software. CONCLUSION: Using half of the exposition dose on a flat-panel detector, an optimized post-processing leads to comparable or better results compared to the conventional film-screen-system concerning the image quality.

Cell cycle regulation during mouse olfactory neurogenesis.

The development of the nervous system requires a strict control of cell cycle entry and withdrawal. The olfactory epithelium (OE) is noticeable by its ability to yield new neurons not only during development but also continuously during adulthood. The aim of our study was to investigate, by biochemical and immunohistochemical methods, which cell cycle regulators are involved in the control of neuron production during OE development and maturity. At birth, olfactory neural progenitors, the basal cells, exhibited a high mitogenic and neurogenic activity, decreasing in the following weeks together with the drop in expression of several cell cycle regulators. p27Kip1 and p18Ink4c, at birth, were expressed in the whole basal cell layer, whereas p16Ink4a, p19Ink4d, and p21Cip1 were rather located in differentiating or mature neurons. CDK inhibitors may thus act sequentially during this developmental neurogenic process. By comparison, in the adult OE, in which most neural precursors were quiescent, these cells still exhibited p18Ink4c expression but only occasionally p27Kip1 expression. It suggests that p18Ink4c may contribute to maintain basal cells in a quiescent state, whereas p27Kip1 expression in these cells may be rather linked to their neurogenic activity, which declines with age. In keeping with this hypothesis, transgenic mice that lacked p27Kip1 expression displayed a higher rate of cell proliferation versus differentiation in their OE. In these mice, a down-regulation of positive cell cycle regulators was observed that may contribute to compensate for the absence of p27Kip1. Taken together, the present data suggest distinct functions for CDK inhibitors, either in the control of cell cycle exit and differentiation during neurogenesis (respectively, p27Kip1 and p19Ink4d) or in the maintenance of a quiescent state in neural progenitors (p18Ink4c) or neurons (p21Cip1) in adults.

[First clinical experience with a full-size, flat-panel detector for imaging the peripheral skeletal system]. / Erste klinische Erfahrungen mit einem grossformatigen Flächendetektorsystem bei Aufnahmen des peripheren Skelettsystems - Teil 1: halbierte Patientendosis -

PURPOSE: This investigation was intended to show that exposures of the peripheral skeleton system can be done with half of the dose used for conventional screen-film systems with a full-size CsI/a-Si flat panel detector. MATERIAL AN METHODS: 120 exposures of the wrist and 100 exposures of the ankle have been made on a full-size flat panel detector system (43 x 43 cm). The patient dose has been reduced by a factor of two compared to conventional images. Five radiologists evaluated every image as a softcopy and a hardcopy image. For the evaluation, a variation of the Visual Grading Analysis (VGA) without reference images was used. For the determination of the patient entrance dose, measurement of a phantom were performed. RESULTS: A dose reduction of about 50 % is possible with the same or even better image quality in routine diagnostics. Only 3 % of the ankle and approx. 21 % of the wrist exposures required a postprocessing. Exposures with implants did not show any artifacts and some of the those achieved better evaluation results compared with exposures without implants. CONCLUSION: A halving of the patient dose is possible with acceptable results for the image quality. The effect of an improved image processing remains to be evaluated. The patient entrance dose is suitable for an evaluation of a radiographic detector and especially for a dose-referred comparison of digital X-ray units.

Region-specific expression of cell cycle inhibitors in the adult brain.

In the adult brain, neural proliferation is almost absent and neurons are generally not renewed. By contrast, in the olfactory organ, olfactory neurons are produced continuously throughout life. To investigate whether specific cell cycle inhibitors are involved in the control of neural quiescence in adulthood, we compared their expression either in different regions of the adult brain weakly or non neurogenic or, for comparison, in the olfactory mucosa. We show that numerous cell cycle inhibitors are expressed in the adult brain either in an ubiquitous fashion (as p19Ink4d) or in specific brain regions (p15Ink4b in the forebrain, p27Kip1 and p21Cip1 in the cerebellum). By contrast p18Ink4c was expressed detectably only in the highly neurogenic olfactory epithelium. The present data suggest that various CDK inhibitors may be involved in a region-specific fashion in the maintenance of nerve cell quiescence in adults.