Three-year follow-up analysis of the short-stitch versus long-stitch technique for elective midline abdominal closure randomized-controlled (ESTOIH) trial.

BACKGROUND: Clinical trials have shown reduced incisional hernia rates 1 year after elective median laparotomy closure using a short-stitch technique. With hernia development continuing beyond the first postoperative year, we aimed to compare incisional hernias 3 years after midline closure using short or long stitches in patients from the ESTOIH trial. METHODS: The ESTOIH trial was a prospective, multicenter, parallel-group, double-blind, randomized-controlled study of primary elective midline closure. Patients were randomized to fascia closure using a short- or long-stitch technique with a poly-4-hydroxybutyrate-based suture. A predefined 3-year follow-up analysis was performed with the radiological imaging-verified incisional hernia rate as the primary endpoint. RESULTS: The 3-year intention-to-treat follow-up cohort consisted of 414 patients (210 short-stitch and 204 long-stitch technique) for analysis. Compared with 1 year postoperatively, incisional hernias increased from 4.83% (20/414 patients) to 9.02% (36/399 patients, p = 0.0183). The difference between the treatment groups at 3 years (short vs. long stitches, 15/198 patients (7.58%) vs. 21/201 (10.45%)) was not significant (OR, 1.4233; 95% CI [0.7112-2.8485]; p = 0.31). CONCLUSION: Hernia rates increased significantly between one and 3 years postoperatively. The short-stitch technique using a poly-4-hydroxybutyrate-based suture is safe in the long term, while no significant advantage was found at 3 years postoperatively compared with the standard long-stitch technique. TRIAL REGISTRY: NCT01965249, registered on 18 October 2013.

Effects of the short-stitch technique for midline abdominal closure: short-term results from the randomised-controlled ESTOIH trial.

PURPOSE: The short-stitch technique for midline laparotomy closure has been shown to reduce hernia rates, but long stitches remain the standard of care and the effect of the short-stitch technique on short-term results is not well known. The aim of this study was to compare the two techniques, using an ultra-long-term absorbable elastic suture material. METHODS: Following elective midline laparotomy, 425 patients in 9 centres were randomised to receive wound closure using the short-stitch (USP 2-0 single thread, n = 215) or long-stitch (USP 1 double loop, n = 210) technique with a poly-4-hydroxybutyrate-based suture material (Monomax®). Here, we report short-term surgical outcomes. RESULTS: At 30 (+10) days postoperatively, 3 (1.40%) of 215 patients in the short-stitch group and 10 (4.76%) of 210 patients in the long-stitch group had developed burst abdomen [OR 0.2830 (0.0768-1.0433), p = 0.0513]. Ruptured suture, seroma and hematoma and other wound healing disorders occurred in small numbers without differences between groups. In a planned Cox proportional hazard model for burst abdomen, the short-stitch group had a significantly lower risk [HR 0.1783 (0.0379-0.6617), p = 0.0115]. CONCLUSIONS: Although this trial revealed no significant difference in short-term results between the short-stitch and long-stitch techniques for closure of midline laparotomy, a trend towards a lower rate of burst abdomen in the short-stitch group suggests a possible advantage of the short-stitch technique. TRIAL REGISTRY: NCT01965249, registered October 18, 2013.

Isolation of primary human B lymphocytes from tonsils compared to blood as alternative source for ex vivo application.

B lymphocytes ('B cells') are components of the human immune system with obvious potential for medical and biotechnological applications. Here, we discuss the isolation of primary human B cells from both juvenile and adult tonsillar material using a two-step procedure based on gradient centrifugation followed by separation on a nylon wool column as alternative to the current gold standard, i.e., negative immunosorting from buffy coats by antibody-coated magnetic beads. We show that the nylon wool separation is a low-cost method well suited to the isolation of large amounts of primary B cells reaching purities ≥ 80%. More importantly, this method allows the preservation of all B cell subsets, while MACS sorting seems to be biased against a certain B cell subtype, namely the CD27+ B cells. Importantly, compared to blood, the excellent recovery yield during purification of tonsillar B cells provides high number of cells, hence increases the number of subsequent experiments feasible with identical cell material, consequently improving comparability of results. The cultivability of the isolated B cells was demonstrated using pokeweed mitogen (PWM) as a stimulatory substance. Our results showed for the first time that the proliferative response of tonsillar B cells to mitogens declines with the age of the donor. Furthermore, we observed that PWM treatment stimulates the proliferation of a dedicated subpopulation and induces some terminal differentiation with ASCs signatures. Taken together this indicates that the proposed isolation procedure preserves the proliferative capability as well as the differentiation capacity of the B cells.

Remote entanglement between a single atom and a Bose-Einstein condensate.

Entanglement between stationary systems at remote locations is a key resource for quantum networks. We report on the experimental generation of remote entanglement between a single atom inside an optical cavity and a Bose-Einstein condensate (BEC). To produce this, a single photon is created in the atom-cavity system, thereby generating atom-photon entanglement. The photon is transported to the BEC and converted into a collective excitation in the BEC, thus establishing matter-matter entanglement. After a variable delay, this entanglement is converted into photon-photon entanglement. The matter-matter entanglement lifetime of 100 µs exceeds the photon duration by 2 orders of magnitude. The total fidelity of all concatenated operations is 95%. This hybrid system opens up promising perspectives in the field of quantum information.

Finite-temperature collective dynamics of a Fermi gas in the BEC-BCS crossover.

We report on experimental studies on the collective behavior of a strongly interacting Fermi gas with tunable interactions and variable temperature. A scissors mode excitation in an elliptical trap is used to characterize the dynamics of the quantum gas in terms of hydrodynamic or near-collisionless behavior. We obtain a crossover phase diagram for collisional properties, showing a large region where a nonsuperfluid strongly interacting gas shows hydrodynamic behavior. In a narrow interaction regime on the BCS side of the crossover, we find a novel temperature-dependent damping peak, suggesting a relation to the superfluid phase transition.

Precision measurements of collective oscillations in the BEC-BCS crossover.

We report on precision measurements of the frequency of the radial compression mode in a strongly interacting, optically trapped Fermi gas of (6)Li atoms. Our results allow for a test of theoretical predictions for the equation of state in the BEC-BCS crossover. We confirm recent quantum Monte Carlo results and rule out simple mean-field BCS theory. Our results show the long-sought beyond-mean-field effects in the strongly interacting Bose-Einstein condensation (BEC) regime.

Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation.

OBJECTIVES: The incidence of obesity-hypoventilation syndrome (OHS) has greatly increased over time, but data on long-term outcome are limited. We investigated survival and prognostic factors in these patients undergoing noninvasive positive pressure ventilation (NPPV). DESIGN: Retrospective descriptive analysis of patients with OHS and NPPV up to 10 years. METHODS: Long-term mortality and predictors of survival were assessed. Additionally, we evaluated changes in lung function, blood gas and laboratory parameters 5.7 +/- 2.5 months after initiation of NPPV. RESULTS: 126 patients (BMI 44.6 +/- 7.8 kg m(-2); PaCO(2) 55.5 +/- 7.7 mmHg) were followed for 41.3 +/- 27.6 months. Upon follow-up, blood gases (daytime and nighttime), as well as pulmonary function improved, whilst haemoglobin and BMI decreased (P < 0.001 each). Adherence to NPPV was high (94.5% continuing NPPV 6.5 +/- 2.3 h day(-1)). All-cause mortality was 12.7%, with 1-, 2- and 5-year survival of 97.1%, 92.0% and 70.2%, respectively. In univariate analysis, patients with PaO(2) <50 mmHg, C-reactive protein > or = 5.1 mg L(-1), leucocytes > or = 7.8 x 10(3) microl(-1), or pH > or = 7.44 at baseline had poor prognosis (P < 0.05 each). In Cox multivariate analysis, PaO(2), pH and leucocytes were independent predictors of mortality. Reduction in nocturnal PaCO(2) by > or =23.0% and haemoglobin at follow-up was associated with improved survival (P < 0.05 each) whilst a decrease in pH was a predictor of increased mortality. In contrast, neither baseline BMI nor its change was linked to survival. CONCLUSION: Gas exchange and lung function in OHS were improved after initiation of NPPV. Hypoxemia, high pH and elevated inflammation markers predicted poor survival. Overall, NPPV was well tolerated and survival was excellent when compared with data from historical matched controls.

Tenascin C and annexin II expression in the process of pancreatic carcinogenesis.

Tenascin C (TNC) is a component of the provisional extracellular matrix (ECM) that characterizes solid tumours. Cell surface annexin II is a high-affinity receptor for large TNC splice variants. The aim of this study was to analyse whether TNC and annexin II play a role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by a rich ECM populated by pancreatic stellate cells, which play a crucial role in pancreatic desmoplasia. The mRNA and protein levels of TNC and of annexin II were analysed in pancreatic tissues by DNA array, quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and immunohistochemistry. TNC large splice variants were detected by RT-PCR. Enzyme linked immunosorbent assay (ELISA) was used to measure TNC levels in serum and culture supernatants. TNC and annexin II mRNA levels were significantly higher in pancreatic cancer tissues than in the normal pancreas. TNC expression was detected with increased frequency in the progression from PanIN-1 lesions to PDAC, and a parallel switch from cytoplasmic to cell surface expression of annexin II was observed. Large TNC transcripts were found in pancreatic cancer and in chronic pancreatitis, but not in the normal pancreas. TNC expression was demonstrated in pancreatic stellate cells, where it could be induced by tumour necrosis factor alpha (TNFalpha), transforming growth factor beta1 (TGF-beta1) and by cancer cell supernatants supplemented with TGF-beta1. In conclusion, the expression of TNC and cell surface annexin II increases in the progression from low-grade PanIN lesions to pancreatic cancer. Pancreatic stellate cells are identified as a source of TNC in pancreatic tissues, possibly under the influence of soluble factors released by the tumour cells.

Targeting XIAP for the treatment of malignancy.

X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family of caspase inhibitors that selectively binds and inhibits caspases-3, -7 and -9, but not caspase-8. As such, XIAP blocks a substantial portion of the apoptosis pathway and is an attractive target for novel therapeutic agents for the treatment of malignancy. Antisense oligonucleotides directed against XIAP are effective in vitro and are currently being evaluated in clinical trials. Small molecule XIAP inhibitors that target the baculovirus IAP repeat (BIR) 2 or BIR 3 domain are in preclinical development and are advancing toward the clinic. This review will discuss the progress being made in developing antisense and small-molecule XIAP inhibitors.

Mutational spectrum of steroid 21-hydroxylase and the genotype-phenotype association in Middle European patients with congenital adrenal hyperplasia.

OBJECTIVE: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotype- phenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. DESIGN AND METHODS: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. RESULTS: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype-phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical- (NC) and even SV-CAH. CONCLUSIONS: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94-99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.

Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a meal-related pattern.

OBJECTIVE: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utilization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail. DESIGN: 24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m(2)) and compared with GH, insulin and glucose levels. METHODS: Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated. RESULTS: An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels. CONCLUSIONS: This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition, GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.

[Patient compliance and efficacy of diagnostic procedures in the surveillance of colorectal cancer: experience from a cancer center]. / Patientencompliance und Stellenwert diagnostischer Verfahren in der Tumornachsorge beim kolorektalen Karzinom: Erfahrungen aus einem Tumorzentrum.

Postoperative surveillance is an important part of the curative therapy of colorectal cancer patients. The effort and effectiveness of these surveillance programs are controversially discussed. We analyzed the practiced follow-up of patients who had undergone a curative resection of colorectal cancer to demonstrate the difficulty to validate the performed surveillance program and to point out possible improvements. For a follow-up period of 37 months (median) we included 530 patients with at least one postoperative examination. 70 patients ended the follow-up prematurely - out of these 56 % quit the surveillance during the first 18 months. Another 68 patients died during the follow-up period. Cancer recurred in 28 % of the patients (n = 109 metastasis, n = 26 local recurrences, 18 patients developed a secondary cancer). 90 % of these recurrences occurred within the first three years. 3525 follow-up examinations took place within 79 months. Patient histories and physical examinations were not helpful for the diagnosis of local recurrences; neither were laboratory routine screenings meaningful. Carcinoembryonic antigen (CEA) and CA 19 - 9 tests, ultrasonographic studies, chest XD-rays and colonoscopic procedures had a higher diagnostic value on the other hand. We demonstrated the problematic nature of the evaluation of different follow-up tests concerning their validity as they were part of a complex postoperative surveillance program. It is also important to point out that the success of the postoperative surveillance depends strongly on the compliance of the patients. To increase this compliance we suggest that the follow-up of patients should be more strongly oriented towards the incidence of recurrences.

Precise determination of 6Li cold collision parameters by radio-frequency spectroscopy on weakly bound molecules.

We employ radio-frequency spectroscopy on weakly bound (6)Li(2) molecules to precisely determine the molecular binding energies and the energy splittings between molecular states for different magnetic fields. These measurements allow us to extract the interaction parameters of ultracold (6)Li atoms based on a multichannel quantum scattering model. We determine the singlet and triplet scattering lengths to be a(s) = 45.167(8)a(0) and a(t) = -2140(18)a(0) (1a(0) = 0.052 917 7 nm), and the positions of the broad Feshbach resonances in the energetically lowest three s-wave scattering channels to be 83.41(15), 69.04(5), and 81.12(10) mT.

Pronounced short stature in a girl with tricho-rhino-phalangeal syndrome II (TRPS II, Langer-Giedion syndrome) and growth hormone deficiency.

We report on a 10-year-old girl with tricho-rhino-phalangeal syndrome type II (TRPS II) and pronounced short stature (-4.8 SD). The patient has an interstitial chromosome 8q24.1 deletion of 12-15 Mb. The deletion spans all genes from CSMD3 to at least ANXA13 including the TRPS1 and EXT1 genes, which are responsible for the TRPS II phenotype. In addition to the features of TRPS II, the patient had growth hormone (GH) deficiency with diminished response in three stimulation tests. Therapy with 0.2 mg GH/kg/week led to an increase of growth velocity from 2.5 to 6.6 cm/year. To our knowledge, such a combination of TRPS II and GH deficiency has not yet been described.

Observation of the pairing gap in a strongly interacting Fermi gas.

We studied fermionic pairing in an ultracold two-component gas of 6Li atoms by observing an energy gap in the radio-frequency excitation spectra. With control of the two-body interactions through a Feshbach resonance, we demonstrated the dependence of the pairing gap on coupling strength, temperature, and Fermi energy. The appearance of an energy gap with moderate evaporative cooling suggests that our full evaporation brought the strongly interacting system deep into a superfluid state.

Collective excitations of a degenerate gas at the BEC-BCS crossover.

We study collective excitation modes of a fermionic gas of (6)Li atoms in the BEC-BCS crossover regime. While measurements of the axial compression mode in the cigar-shaped trap close to a Feshbach resonance confirm theoretical expectations, the radial compression mode shows surprising features. In the strongly interacting molecular BEC regime, we observe a negative frequency shift with increasing coupling strength. In the regime of a strongly interacting Fermi gas, an abrupt change in the collective excitation frequency occurs, which may be a signature for a transition from a superfluid to a collisionless phase.

Crossover from a molecular Bose-Einstein condensate to a degenerate Fermi gas.

We demonstrate a reversible conversion of a 6Li2 molecular Bose-Einstein condensate to a degenerate Fermi gas of atoms by adiabatically crossing a Feshbach resonance. By optical in situ imaging, we observe a smooth change of the cloud size in the crossover regime. On the Feshbach resonance, the ensemble is strongly interacting and the measured cloud size is 75(7)% of the one of a noninteracting zero-temperature Fermi gas. The high condensate fraction of more than 90% and the adiabatic crossover suggest our Fermi gas to be cold enough to form a superfluid.

Validation of a mathematical model predicting the response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency.

OBJECTIVE: To validate a mathematical model developed by Ranke et al. (J Clin Endocrinol Metab 1999;84:1174-7783) to predict the GH response during the first years of GH replacement therapy. PATIENTS AND METHODS: 38 children with idiopathic GH deficiency (GHD) met all inclusion criteria for the prediction model, but the group differed in some characteristics from the cohort from which the model was derived. RESULTS: Using the model for the 1st year including maximum GH after stimulation and the equation for the 6th year, the predicted value corresponded well with actual height gain. Differences were found when the growth response of the 1st year excluding maximum GH and that of the 2nd-5th year were calculated, resulting in a significant underestimation of actual height gain (-0.63 to -1.07 cm/year). CONCLUSION: The mathematical prediction model tended to underpredict the growth response to GH treatment in our patients with pronounced GHD. The severity of GHD seems to be an important parameter for the 1st year prediction.

[Modern operating room management in the workflow of surgery. Spectrum of tasks and challenges of the future]. / Modernes Operationsmanagement im Workflow Operation. Aufgabenspektrum und Herausforderungen der Zukunft.

The operating unit is one of the cost-intensive facilities in a surgical clinic with a pacemaking function for most of the internal procedures. The power of performance of the operating unit is based on the cooperation of all disciplines and professions involved. The key to management of the operating unit is not only to coordinate the daily procedures, but also to interact with support personnel. To ensure successful OR management, the internal structure of the OR must fit the clinical tasks and the available quantity of personnel in each profession must be coordinated. Sufficient utilization of resources and equipment must be guaranteed without cost-intensive over-capacities and patient flow must be orientated to OR capacities. The development of such a business structure requires the management to clearly define the goal, to know the actual on-site data in detail with regard to the idiosyncratic workings of each specialty and to clearly assign the competence of each member of the team working in the OR. Coordination of the operating unit is the main task of OR management, which must ensure the following: transparent and coordinated schedule management in the various operative specialties, goal-directed changes of the schedule with incorporation of emergencies, as well as effective organization of staff. In order to realize these tasks, it is reasonable to implement interdisciplinary rules of procedures. In addition, the assignment of a neutral decision-making body within the OR and the creation of an information center for all OR personnel. The challenge of OR organization in the future is to implement more effective documentation systems and active controlling within the OR. One can ensure adequate utilization of resources in the OR with prospectively oriented planning. Better transparency of operations in the OR contributes to increased efficiency. Implementation of quality management is the foundation for a successfully operating surgical hospital. Not only the productivity of individual members of the staff, but also the precise documentation of the quality of results will become important parameters in a successful surgical hospital, whose nucleus is the OR.

Bose-Einstein condensation of molecules.

We report on the Bose-Einstein condensation of more than 10(5) Li2 molecules in an optical trap starting from a spin mixture of fermionic lithium atoms. During forced evaporative cooling, the molecules are formed by three-body recombination near a Feshbach resonance and finally condense in a long-lived thermal equilibrium state. We measured the characteristic frequency of a collective excitation mode and demonstrated the magnetic field-dependent mean field by controlled condensate spilling.