[Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders]. / Prävalenz schlafbezogener Atmungsstörungen bei stationären Patienten mit psychischen Erkrankungen.

BACKGROUND: Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders. METHODS: In 10 psychiatric hospitals in Germany and 1 hospital in Switzerland, a total of 249 inpatients underwent an 8­channel sleep polygraphy to investigate the prevalence of sleep apnea in this group of patients. RESULTS: With a conspicuous screening result of 23.7% of the subjects, a high prevalence of sleep-related breathing disorders was found to occur among this group of patients. Male gender, higher age and high body mass index (BMI) were identified as positive risk factors for the detection of OSAS. DISCUSSION: The high prevalence indicates that sleep apnea is a common sleep disorder among psychiatric patients. Although OSAS can lead to substantial disorders of the mental state and when untreated is accompanied by serious somatic health problems, screening procedures are not part of the routine work-up in psychiatric hospitals; therefore, sleep apnea is presumably underdiagnosed in psychiatric patients. In view of the results of this and previous studies, this topic complex should be the subject of further research studies.

Unilateral laminoplasty with lateral mass screw fixation for less invasive decompression of the cervical spine: a biomechanical investigation.

PURPOSE: To compare the stabilization behavior of additional unilateral mass screw fixation with current standard procedures in patients with cervical spondylotic myelopathy (CSM) in a biomechanical study. METHODS: Ten human C2-C7 cervical specimens were tested under various segment conditions: native (NAT), laminoplasty (LP), laminoplasty with unilateral (LPU) or bilateral (LPB) stabilization, laminectomy with bilateral stabilization (LCB), and laminectomy. The instrumented level was from C3 to C6. For each segment condition, in vitro flexibility tests were performed using a spinal simulator and an applied load of ±2.5 Nm. The three-dimensional kinematics of the entire cervical segment in three main loading directions [flexion-extension (FE), lateral bending (LB), and axial rotation (AR)] was measured with an ultrasonic motion analysis system. Analysis of variance followed by a post hoc test was used to determine differences under the specific segment conditions to assess the parameters range of motion (ROM) and neutral zone (NZ). RESULTS: For FE, the total ROM of laminoplasty (-6.3% difference to NAT) and laminectomy (+6.4%) remained at the level of native (p > 0.56), whereas the instrumentations LPU (-37.1%), LPB (-44%), and LCB (-43.2%) lead to significant reductions (p < 0.01) without significant differences in LPU to LPB and LCB (p > 0.38). The same results were found with LB. For AR, the stabilization of all instrumentations was less pronounced, but had the same tendency seen for FE and AR. The results for the NZ showed equivalent values as that for ROM. CONCLUSION: The degree of stabilization was as expected for LC and LCB; namely, no stabilization for LC and maximal stabilization for LCB. LPU exhibited almost the same degree of stabilization as LCB. LPU could be a new treatment option for less invasive decompression for multilevel CSM.

Prognostic significance of neuroepithelial transforming gene 1 in adenocarcinoma of the oesophagogastric junction.

BACKGROUND: Neuroepithelial transforming gene 1 (NET1) mediates tumour invasion and metastasis in a number of cancers, including gastric adenocarcinoma. It is an indicator of poor prognosis in breast cancer and glioma. This study examined NET1 expression and its prognostic significance in patients with adenocarcinoma of the oesophagogastric junction (AOG). METHODS: NET1 expression was measured by immunohistochemistry in a tissue microarray, constructed from biobanked tissue collected over a 10-year interval, and linked to a prospectively maintained clinical database. RESULTS: Using the Siewert classification for AOG, type I tumours expressed significantly higher levels of NET1, with lowest expression in type III and intermediate levels in type II (P = 0.001). In patients with AOG type III, NET1-positive patients were more likely to be female (P = 0.043), have advanced stage cancer (P = 0.035), had a higher number of transmural cancers (P = 0.006) and had a significantly higher median number of positive lymph nodes (P = 0.029). In this subgroup, NET1-positive patients had worse median overall (15 versus 23 months; P = 0·025) and disease-free (11 versus 36 per cent; P = 0.025) survival compared with NET1-negative patients. CONCLUSION: Although existing data show differences in clinical and prognostic indices across AOG subtypes, there are no studies showing differences in tumour biology. These data suggest NET1, a known mediator of an aggressive tumour phenotype in a number of gastrointestinal cancers, is expressed differentially across AOG subtypes and may be of prognostic significance in the clinical management of this condition.

Cortical thickness of superior frontal cortex predicts impulsiveness and perceptual reasoning in adolescence.

Impulsiveness is a pivotal personality trait representing a core domain in all major personality inventories. Recently, impulsiveness has been identified as an important modulator of cognitive processing, particularly in tasks that require the processing of large amounts of information. Although brain imaging studies have implicated the prefrontal cortex to be a common underlying representation of impulsiveness and related cognitive functioning, to date a fine-grain and detailed morphometric analysis has not been carried out. On the basis of ahigh-resolution magnetic resonance scans acquired in 1620 healthy adolescents (IMAGEN), the individual cortical thickness (CT) was estimated. Correlations between Cloninger's impulsiveness and CT were studied in an entire cortex analysis. The cluster identified was tested for associations with performance in perceptual reasoning tasks of the Wechsler Intelligence Scale for Children (WISC IV). We observed a significant inverse correlation between trait impulsiveness and CT of the left superior frontal cortex (SFC; Monte Carlo Simulation P<0.01). CT within this cluster correlated with perceptual reasoning scores (Bonferroni corrected) of the WISC IV. On the basis of a large sample of adolescents, we identified an extended area in the SFC as a correlate of impulsiveness, which appears to be in line with the trait character of this prominent personality facet. The association of SFC thickness with perceptual reasoning argues for a common neurobiological basis of personality and specific cognitive domains comprising attention, spatial reasoning and response selection. The results may facilitate the understanding of the role of impulsiveness in several psychiatric disorders associated with prefrontal dysfunctions and cognitive deficits.

The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care--an observational analysis on non-small-cell lung cancer patients.

PURPOSE: To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective. RESULTS: A total of 120 consecutive NSCLC patients (mean age, 63.0 ± 8.4 (SD) years; men, 64.2%; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3%; tumour stage III/IV, 85%; history of comorbidity, 93.3%) receiving 130 CT lines were evaluated. 80% of CT lines were associated with grade 3 or 4 ADRs, 22.3% developed potential life-threatening complications, 77.7% were associated with at least one hospital stay (inpatient, 63.9%; outpatient/day clinic 39.2%, ICU 6.9%), with a mean cumulative number of 12.8 (±14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to €3,366 (€1,406) and were found to be higher for first-line compared to second-line treatment: €3,677 (€1,599) vs. €2,475 (€518). TMC-TL were particularly high in CT lines with ICU care €12,207 (€9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with ICU care accounted for 25% of total expenses (€109,861 out of €437,580). CONCLUSIONS: In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients' clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.

Health resource consumption and costs attributable to chemotherapy-induced toxicity in German routine hospital care in lymphoproliferative disorder and NSCLC patients.

BACKGROUND: Multidrug chemotherapy (CT) is still associated with relevant side-effects. We assessed, under current practice patterns, frequency and severity of CT-induced toxicity and its economic consequences. PATIENTS AND METHODS: Prospective, multicentre, longitudinal, observational cohort study with lymphoproliferative disorder (LPD) and non-small-cell lung cancer (NSCLC) patients, receiving first- or second-line (immuno-) CT (excluding myeloablative CT). Data were collected from patient interviews and preplanned chart reviews. Costs in 2007 euros are presented from the provider perspective. RESULTS: Two hundred and seventy-three patients (n = 153 LPD; n = 120 NSCLC) undergoing a total of 1004 CT cycles were assessable (age ≥65 years, 40%; female, 36%; Eastern Cooperative Oncology Group performance status ≥2, 11%; tumour stage ≥III, 56%; history of comorbidity, 80%). Fifty percent of cycles were associated with grade 3/4 toxicity and 37% (n = 371) with at least one hospital stay (outpatient/day care n = 154; intensive care n = 19). Mean (median) toxicity-related costs amounted to €1032 (€86) per cycle. Costs rose exponentially with the number of grade 3/4 adverse drug reactions (ADRs) and were highest in cycles affected by more than four ADRs, €10 881 (€5455); in cycles with intensive care, €14 121 (€8833); and in cycles affected by grade 3/4 infections and febrile neutropenia/leukopenia, €7093 (€4531) and €5170 (€2899), respectively. Five percent of CT cycles accounted for 56% of total expenses. CONCLUSIONS: Individualised supportive care strategies are needed. Future research should focus on identifying toxicity clusters and patient characteristics predictive for high costs.

The effect of design parameters of dynamic pedicle screw systems on kinematics and load bearing: an in vitro study.

As an alternative treatment for chronic back pain due to disc degeneration motion preserving techniques such as posterior dynamic stabilization (PDS) has been clinically introduced, with the intention to alter the load transfer and the kinematics at the affected level to delay degeneration. However, up to the present, it remains unclear when a PDS is clinically indicated and how the ideal PDS mechanism should be designed to achieve this goal. Therefore, the objective of this study was to compare different PDS devices against rigid fixation to investigate the biomechanical impact of PDS design on stabilization and load transfer in the treated and adjacent cranial segment. Six human lumbar spine specimens (L3-L5) were tested in a spine loading apparatus. In vitro flexibility testing was performed by applying pure bending moments of 7.5 Nm without and with additional preload of 400 N in the three principal motion planes. Four PDS devices, "DYN" (Dynesys(®), Zimmer GmbH, Switzerland), "DSS™" (Paradigm Spine, Wurmlingen, Germany), and two prototypes of dynamic rods, "LSC" with a leaf spring, and "STC" with a spring tube (Aesculap AG, Tuttlingen, Germany), were tested in comparison to a rigid fixation device S(4) (Aesculap AG, Tuttlingen, Germany) "RIG", to the native situation "NAT" and to a defect situation "DEF" of the specimens. The instrumented level was L4-L5. The tested PDS devices comprising a stiffness range for axial stiffness of 10 N/mm to 230 N/mm and for bending stiffness of 3 N/mm to 15 N/mm. Range of motion (ROM), neutral zone (NZ), and intradiscal pressure (IDP) were analyzed for all instrumentation steps and load cases of the instrumented and non-instrumented level. In flexion, extension, and lateral bending, all systems, except STC, showed a significant reduction of ROM and NZ compared to the native situation (p < 0.05). Furthermore, we found no significant difference between DYN and RIG (p > 0.1). In axial rotation, only DSS and STC reduced the ROM significantly (p < 0.005) compared to the native situation, whereas DYN and LSC stayed at the level of the native intersegmental rotation (p > 0.05). A correlation was found between axial stiffness and intersegmental stabilization in the sagittal and frontal plane, but not in the transversal plane where intersegmental stabilization is mainly governed by the systems' ability to withstand shear loads. Furthermore, we observed the systems' capacity to reduce IDP in the treated segment. The adjacent segment does not seem to be affected by the stiffness of the fixation device under the described loading conditions.

[Effect of lumbar hybrid instrumentation and rigid fusion on the treated and the adjacent segments. A biomechanical study]. / Auswirkung der lumbalen Hybridinstrumentierung und der rigiden Fusion auf das versorgte und anschließende Segment. Eine biomechanische Untersuchung.

BACKGROUND: Degeneration of the upper adjacent segment after operative treatment of degenerative spinal diseases of the lumbar spine (degenerative disc disease DDD) is an unsolved problem. There is also no consensus on whether a rigid or dynamic treatment of DDD should be carried out to protect the segments. This study was carried out to evaluate the effect of bisegmental rigid 360° fusion and bisegmental hybrid fusion on the treated segment as well as on the upper adjacent segment under the aspect of segment protection. MATERIAL AND METHODS: A total of six human spinal column preparations (L2-5) were tested under native conditions (NAT), with bisegmental rigid fusion (RIG 360°) and with hybrid fusion (Hybrid) in all three movement directions under physical load and with an preload. The range of motion (ROM) and neutral zone (NZ) were evaluated. The intradiscal pressure (IDP) was measured in the upper adjacent segment (OAS). RESULTS: The RIG 360° led to a significant reduction in movement in all directions compared to NAT but Hybrid only in lateral bending (LB). In the OAS the NZ was showed a much greater increase than the ROM. The RIG 360° showed an increase of the NZ in flexion-extension of 86.8% and in LB of 49.6% as well as a significant increase in axial rotation of 52.5%. The increase in the Hybrid was not significant compared to NAT in all directions. Pressure measurements in OAS showed no significant differences for RIG 360° and for Hybrid compared to NAT for both load scenarios. DISCUSSION: The range of motion of the treated segments for Hybrid were close to NAT in comparison to RIG 360° indicating a segment-protective effect. The hypothesis that rigid fusion has a significant effect on intersegmental mobility and the increase in intradiscal pressure in the upper adjacent segment could not be confirmed. The data indicate that the primary effect of fusion on the adjacent segment is very low but the fusion-linked increased frequency of extreme loads of the OAS falling within the significance level leads to degeneration. Even if the NZ values for Hybrid and RIG 360° do not significantly differ from NAT, the NZ alterations between the instrumentations tend to be strongly shifted in favor of Hybrid. CONCLUSIONS: The data confirm that the clear and sometimes significant alterations of the NZ can be an essential factor for development of adjacent segment degeneration. A dynamic conclusion of instrumentation in the sense of a topping-off would appear to be useful if pathoanatomical indications for an intervertebral disc prosthesis are present.

Novel double injection technique for sentinel lymph node biopsy in oral cancer.

The development of new lymphatic tracers and the advancement of hybrid tracers, such as indocyanine green (ICG)-Nanocoll (GE Healthcare), represent an exciting step in the future of sentinel lymph node biopsy (SLNB). These tracers aim to improve our ability to detect sentinel lymph nodes by enhancing their localisation. The aim of this study was to assess the performance of a novel dual tracer, double injection technique of ICG-'cold'-Nanocoll and radiolabelled Nanocoll, in SLNB for early-stage oral cancer. A double injection technique was performed first using 99mTc-Nancoll prior to sentinel node imaging followed by ICG-'cold'-Nanocoll injection in theatre. Analysis involved examination of the number, labelling, and location of the nodes harvested, sentinel node status, survival analysis, false negative rate, and complications associated with use of the technique. ICG 'cold' Nanocoll results showed concordance of fluorescence and radioactivity detection in 74 nodes in 24 patients. Most importantly, all nodes found positive for metastasis (6 nodes) were discovered to be both 'hot' and fluorescent; 74 nodes removed were both 'hot' and fluorescent, eight fluorescent only and six 'hot' only. Our results indicate that two sets of tracer injections given at two different time points will flow to the same sentinel nodes. This double labelling increased our confidence that the retrieved node was a sentinel node.

Do we have a robust method for preoperative tumour depth assessment for oral cavity tumours with clinically negative necks?

Tumour depth is an important prognostic factor in head and neck cancer and has recently been included in the eighth edition of the Union for International Cancer Control TNM classification of malignant tumours for oral squamous cell carcinoma (OSCC). It is important to appraise the accuracy of depth assessments; however, there is little current evidence in the literature. Accurate depth assessment is particularly pertinent in cT1-T2N0 OSCC where it may influence neck management. A retrospective study was performed at two tertiary referral centres, in which surgically treated patients with cT1-T4N0 OSCC were audited. Preoperative tumour depth assessments from multimodality radiological staging scans were compared with the final histopathological depth. The predictive accuracy of intraoral ultrasound (IOUS), computed tomography (CT), and magnetic resonance imaging (MRI) for tumour depth was evaluated. Accuracy to within 3mm of the histopathological depth was seen in 56.7% of MRI scans and 57.1% of CT scans. IOUS appeared to have superior prediction, with 78.2% of measurements within 3mm. Over one third of CT and MRI imaging failed to detect a lesion; IOUS scans detected the lesions in all of these case. In conclusion, the reliability of preoperative imaging assessment of tumour depth should be considered when recommending treatment.

Neck failure following pathologically node-negative neck dissection (pN0) in oral squamous cell carcinoma: a systematic review and meta-analysis.

Due to the risk of occult cervical metastasis, elective neck dissection (END) is recommended in the management of patients with early oral cavity squamous cell carcinoma (OSCC) and a clinically node-negative (cN0) neck. This paper presents a systematic review and meta-analysis of studies that recorded isolated regional recurrence (RR) in the pathologically node-negative neck dissection (pN0) neck following END in order to quantify the failure rate. Pubmed and Ovid databases were systematically searched for relevant articles published between January 2009 and January 2019. Studies reporting RR following END in patients with OSCC who had no pathological evidence of lymph node metastasis were eligible for inclusion in this meta-analysis. In addition, a selection of large head and neck units were invited to submit unpublished data. Search criteria produced a list of 5448 papers, of which 18 studies met the inclusion criteria. Three institutions contributed unpublished data. This included a total of 4824 patients with median follow-up of 34 months (2.8 years). Eight datasets included patients staged T1-T4 with RR 17.3% (469/2711), 13 datasets included patients staged T1-T2 with RR 7.5% (158/2113). Overall across all 21 studies, isolated neck recurrence was identified in 627 cases giving a RR of 13.0% (627/4824) on meta-analysis. Understanding the therapeutic effectiveness of END provides context for evaluation of clinical management of the cN0 in these patients. A pathologically negative neck does not guarantee against future recurrence.

Does night-time cortisol excretion normalize in the long-term course of depression?

INTRODUCTION: While there is extensive literature on HPA system activity in acutely depressed patients, there is only limited information about the presence of hypercortisolemia during the interepisode interval of affective disorders. We hypothesized an increase in HPA system activity in depressed patients compared to controls, and proposed that night-time cortisol excretion during follow-up will depend on clinical outcome. METHODS: We measured night-time cortisol excretion in 27 patients during an acute episode of major depression as well as a 20-week follow-up. 40 healthy subjects served as control group. RESULTS: During the acute episode depressed patients showed increased levels of night-time cortisol excretion compared to healthy controls. Both, patients with full and sustained remission (n=8) as well as patients with incomplete remission or relapse (n=19) showed declining cortisol excretion in night-time urine during follow-up. At the end of follow-up cortisol excretion did not differ between patients with affective disorder and healthy controls. DISCUSSION: Irrespective of residual depressive symptoms, HPA system activity declines after the generally investigated acute depressive episode.

[Retrospective study--pregnancy after assisted medical reproduction from 2001 to 2009 at the Central Hospital of Luxembourg (first section)]. / Etude retrospective--suivis de grossesses après Procréation Médicalement Assistée (PMA) de 2001 à 2009 au Centre Hospitalier de Luxembourg (1re partie).

Retrospective study on a nine year ART practice focusing on pregnancy outcomes and multiple pregnancies, their complications, the gestational duration, delivery options, the new born weights and health statements til the age of two. Post ART pregnancies seem to have an increased complication rate; multiple births are more frequent than with spontaneous conception. The first chapter deals with the entire group. The second chapter analyses several sub-groups according to the ART method employed. The results are compared to publications in PubMed and Medline.

[Retrospective studies of pregnancies after assisted medical reproduction from 2001-2009 and Central Hospital in Luxembourg (part 2)]. / Etude rétrospective--suivis de grossesses après Procréation Médicalement Assistée (PMA) de 2001 à 2009 au Centre Hospitalier de Luxembourg (2e partie).

The first chapter analyses the ART methods of the Centre Hospitalier of Luxembourg, in the department of reproductive medicine between 2001 and 2009. The second chapter examines the techniques individually, their influence on pregnancy outcomes, the complications on offsprings and their health. The results coincide with literature in that risks are acceptable as long as good medical and biological conditions are maintained. Multiple pregnancies remain the most frequent complication, particularly once out of IVF. These are analysed separately as well as the pregnancies after egg and semen donation.

Influence of Irradiation Temperature on Oxidative and Network Properties of X-Ray Cross-Linked Vitamin E Stabilized UHMWPE for Hip Arthroplasty.

Previous studies have shown that increased cross-link density, reduced free radicals, and increased antioxidant grafting resulting from electron-beam irradiation at elevated temperatures improved the wear performance and the oxidative stability of vitamin E blended UHMWPE. The current study explores the impact of elevated irradiation temperature on vitamin E blended UHMWPE using X-ray. We hypothesize that the effects of temperature would be similar to those observed after electron-beam irradiation due to the relatively high dose rate of X-rays. Two X-ray doses of 80 and 100 kGy and two irradiation temperatures, that is, room temperature and 100°C were considered. The reference was Vitelene®, a vitamin E stabilized polyethylene cross-linked with 80 kGy by e-beam at 100°C. Oxidation index and oxidation induction time, as well as cross-link density, gel fraction, and trans-vinylene index, were determined, as the oxidative and network properties are decisive for the long-term implant performance. Gel fraction and oxidation induction time were significantly improved subsequently to warm irradiation in comparison with the material irradiated at room temperature. In conclusion, X-ray irradiation at elevated temperatures resulted in an increase of cross-linking and oxidative resistance of vitamin E stabilized polyethylene comparable to those of e-beam irradiated UHMWPE.

[Guideline for radioimmunotherapy of CD20+ follicular B-cell non-Hodgkin's lymphoma]. / Leitlinie für die Radioimmuntherapie des CD20-positiven follikulären B-Zell-Non-Hodgkin-Lymphoms.

This guideline is a prerequisite for the quality management in the treatment of non-Hodgkon-lymphomas in patients with relapsed or refractory follicular lymphoma after rituximab therapy and as consolidation therapy after first remission following CHOP like treatment using radioimmunotherapy. It is based on an interdisciplinary consensus and contains background information and definitions as well as specified indications and detailed contraindications of treatment. Essential topics are the requirements for institutions performing the therapy. For instance, presence of an expert for medical physics, intense cooperation with all colleagues committed to treatment of lymphomas, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with those colleagues (hemato-oncologists) who propose, in general, radioimmunotherapy under consideration of the development of the disease.

Metabolic modeling of microbial strains in silico.

The large volume of genome-scale data that is being produced and made available in databases on the World Wide Web is demanding the development of integrated mathematical models of cellular processes. The analysis of reconstructed metabolic networks as systems leads to the development of an in silico or computer representation of collections of cellular metabolic constituents, their interactions and their integrated function as a whole. The use of quantitative analysis methods to generate testable hypotheses and drive experimentation at a whole-genome level signals the advent of a systemic modeling approach to cellular and molecular biology.

1.3 microm quantum dot laser in coupled-cavity-injection-grating design with bandwidth of 20 GHz under direct modulation.

Using a multi section laser in coupled cavity injection grating design based on 1.3 microm InGaAs/GaAs quantum dot (QD) active region we were able to enhance the 3 dB modulation bandwidth well beyond the inherent material modulation bandwidth. The material bandwidth was determined by measurements on distributed feedback (DFB) devices to approximately 8 GHz. The special multisectional design allows interaction between the lasing mode and a second mode used as catalyst and enables a high resonance frequency of the device. Based on active QD material this approach allowed us to reach a cut off frequency of 20 GHz in the small signal response of the device.