Polychrome Bone Fluorescence: A valuable diagnostic tool for 4th degree calvarial burns. A Case report.

4th degree calvarial burns are complex in management with regards to determining bone vitality and subsequent choice of defect coverage. Distinguishing viable and nonviable bone can be challenging. Tetracycline bone fluorescence is well described and in common use in maxillofacial patients with bisphosphonate osteonecrosis and has been reported in septic orthopedic surgery specifically periprosthetic joint infection. On the basis that viable bone fluoresces, the concept of polychrome fluorescence was extrapolated as a diagnostic tool for calvarial burns. Bone fluorescence presents an efficient, non-invasive, and cost-effective diagnostic tool delineating exact necrotic margins in 4th degree burns ensuring targeted bone sparing debridement. This report describes the use of polychrome bone fluorescence as an intra-operative tool including a single-centre case report with 4th degree calvarial burns.

A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects.

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

Early Assessment of Impact of Increased Value Added Tax on Smoking Behaviors and Financing among Adult Smokers in Saudi Arabia.

Background: Cigarette smoking has been identified as most perilous risk factor for several health ailments. Increased price may discourage smoking habits. There is limited literature available on impact of price rise on smoking behaviors in Saudi Arabia, which is the fourth largest importer of cigarettes and this study assessed the impact of tax increase (in 2020) on smoking behaviors. Methods: A cross-sectional survey was carried out between July 2021 and December 2021.i.e.one year after new value added tax (VAT) system came into force. Data was collected with 14-item pretested questionnaire from 721 adult smokers in Al-Jouf Region of Saudi Arabia selected through stratified cluster ransom sampling. We measured effects of tax increase on smoking behaviors, its impact on decision to quit and perceived health improvements as outcome variables. Results: Nearly 40% of the respondents said that increased price lead them to smoke less number of cigarettes per day (P=0.000), decreased smoking improved their health in terms of breathing capacity, mood, ability to exercise and sleep in hierarchy. 67.4% of the participants are currently thinking of quitting smoking due to increased prices (P=0.001) and logistic regression models identified reduced smoking due to tax rise (Odds=5.68), improvement in health (Odds=2.94) and excess spending of above 20% (Odds=1.72) significantly associated with intentions to quit smoking. Conclusion: Increased price of cigarettes due to VAT significantly decreased smoking behaviors and has impact on smokers' decision to quit smoking. Future studies needed to assess the long-term effect of increased tax on smoking behaviors and its relapse.

Invasive electrical stimulation in the treatment of avascular osteonecrosis of the femoral head - mid-term results.

The study aimed to evaluate the outcomes of osteonecrosis of the femoral head (ONFH) in adults after surgical treatment including invasive electromagnetic osteostimulation (E-Stim). Further, the influence of disease stage and several comorbidities on the joint preservation rate should be examined. Sixty patients (66 hip joints) with ONFH were included in this retrospective cross-sectional analysis (mean follow-up: 58 months, 19-110 months). Potential ONFH risk factors and comorbidities (ONFH stage, age, sex, alcohol, smoking, cortisone medication, chemotherapy) were recorded. The influence of specific parameters on the joint preservation rates was evaluated by a multivariate logistic regression analysis. Finally, patients with preserved hip joints underwent an assessment of their last available X-rays. The joint preservation rate depended on the initial ONFH Steinberg stage (I+II: 82.8%, III: 70.8%, ≥ IVa: 38.5%). Initially collapsed ONFH (p ≤ 0.001) and cortisone therapy (p = 0.004) significantly decreased the joint preservation rates. In case of progressed ONFH, the presence of ≥ 2 risk factors resulted in higher THA conversion rates (stage III: OR 18.8; stage ≥IVa: OR 12). In 94% of the available X-rays, the ONFH stage improved or did not progress. No complications could be attributed to the E-Stim device or procedure. The present surgical protocol including minimally invasive E-Stim revealed high joint preservation rates for non-collapsed ONFH after mid-term postoperative follow-up. Especially in progressed ONFH, the-risk profile seems to be crucial and hence, for joint preserving surgery, careful patient selection is recommended.

Novel approach to estimate distraction forces in distraction osteogenesis and application in the human lower leg.

PURPOSE: In distraction osteogenesis (DO) of long bones, new bone tissue is distracted to lengthen limbs or reconstruct bone defects. However, mechanical boundary conditions in human application such as arising forces are mainly based on limited empirical data. Our aim was the numerical determination of the callus distraction force (CDF) and the total distraction force (TDF) during DO in the tibia of adults to advance the understanding of callus tissue behavior and optimize DO procedures. METHOD: We implemented a mathematical model based on an animal experiment to enable the calculation of forces arising while distracting callus tissue, excluding the influence of surrounding soft tissue (muscles, skin etc.). The CDF progression for the distraction period was calculated using the implemented model and varying distraction parameters (initial gap, area, step size, time interval, length). Further, we estimated the CDF based on reported forces in humans and compared the results to our model predictions. In addition, we calculated the TDF based on our CDF predictions in combination with reported resisting forces due to soft tissue presence in human cadavers. Finally, we compared the progressions to in vivo TDF measurements for validation. RESULTS: Due to relaxation, a peak and resting CDF is observable for each distraction step. Our biomechanical results show a non-linear degressive increase of the resting and peak CDF at the beginning and a steady non-linear increase thereafter. The calculated resting and peak CDF in the tibial metaphysis ranged from 0.00075 to 0.0089 N and 0.22-2.6 N at the beginning as well as 20-25 N and 70-75 N at the end of distraction. The comparison to in vivo data showed the plausibility of our predictions and resulted in a 10-33% and 10-23% share of resting CDF in the total resting force for bone transport and elongation, respectively. Further, the percentage of peak CDF in total peak force was found to be 29-58% and 27-55% for bone transport and elongation, respectively. Moreover, our TDF predictions were valid based on the comparison to in vivo forces and resulted in a degressive increase from 6 to 125 N for the peak TDF and from 5 to 76 N for the resting TDF. CONCLUSION: Our approach enables the estimation of forces arising due to the distraction of callus tissue in humans and results in plausible force progressions as well as absolute force values for the callus distraction force during DO. In combination with measurements of resisting forces due to the presence of soft tissue, the total distraction force in DO may also be evaluated. We thus propose the application of this method to approximate the behavior of mechanical callus properties during DO in humans as an alternative to in vivo measurements.

Subject specific finite element modelling of periprosthetic femoral fractures in different load cases.

Periprosthetic femoral fractures (PFF) around total hip replacements are one of the biggest challenges for orthopaedic surgeons. To understand the risk factors and formation of these fractures, the development of a reliable finite element (FE) model incorporating bone failure is essential. Due to the anisotropic and complex hierarchical structure of bone, the mechanical behaviour under large strains is difficult to predict. In this study, a state-of-the-art subject specific FE modelling technique for bone is utilised to generate and investigate PFF. A bilinear constitutive law is applied to bone tissue in subject specific FE models of five human femurs which are virtually implanted with a straight hip stem to numerically analyse PFF. The material parameters of the models are expressed as a function of bone ash density and mapped node wise to the FE mesh. In this way the subject specific, heterogeneous structure of bone is mimicked. For material mapping of the parameters, computed tomography (CT) images of the original fresh-frozen femurs are used. Periprosthetic fractures are generated by deleting elements on the basis of a critical plastic strain failure criterion. The models are analysed under physiological and clinically relevant conditions in two different load cases re-enacting stumbling and a sideways fall on the hip. The results of the analyses are quantified with experimental data from previous work. With regard to fracture pattern, stiffness and failure load the simulations of the load case stumbling delivered the most stable and accurate results. In general, mapping of material properties was found to be an appropriate way to reproduce PFF with finite element models.

Novel method for determining bone dimensions relevant for longitudinal and transverse distraction osteogenesis and application in the human tibia and fibula.

BACKGROUND: In distraction osteogenesis (DO) of long bones, new bone tissue is formed and distracted to lengthen limbs or reconstruct bone defects. However, certain anthropometric quantities relevant for biomechanical modelling of DO are unknown, such as areas where new bone tissue is formed. We developed a novel method to facilitate the determination of these distraction areas (DA), which we applied in the tibia and fibula of adults for longitudinal and transverse DO to advance knowledge of anatomical boundary conditions. METHODS: CT data sets of 21 adult human tibiae and 24 fibulae were selected for investigation. Volumetric models were created utilizing image segmentation. The DA for longitudinal DO was determined in a CAD environment using the total bone cross section in the proximal, central and distal diaphysis of the tibia and fibula. Additionally, the medullary canal area was determined in the fibula. Furthermore, we measured the total DA and medullary canal DA for transverse distraction using a longitudinally split fibula with an osteotomy length of 8, 12, 16 and 20 cm. The osteotomy plane was oriented in medial and anteromedial direction. Finally, Spearman analyses were conducted to assess the correlation between bone length and DA. RESULTS: For longitudinal DO, the mean total DAs were 878, 535 and 482 mm2 in the tibia and 132, 153, 124 mm2 in the fibula for the proximal, central and distal diaphysis, respectively. Regarding transverse distraction, the mean total DAs for a medial and anteromedial osteotomy plane orientation were 962, 1423, 1868 and 2306 mm2 as well as 925, 1387, 1844, 2279 mm2 for an osteotomy length of 8, 12, 16 and 20 cm, respectively. Weak, positive, and non-significant correlations were observed when correlating bone length and DA in the tibia and fibula. CONCLUSIONS: Quantification of DAs and hence distracted callus tissue in DO advances anatomical knowledge and improves biomechanical modelling by adding a parameter which cannot be approximated based on bone length.

In vitro effect of autologous platelet-rich plasma on H2 O2 -induced oxidative stress in human spermatozoa.

BACKGROUND: Among new therapies emerging in the medical field, the use of platelet-rich plasma (PRP) in human reproduction has not yet been explored. OBJECTIVES: This study aimed at investigating the effect of autologous PRP on sperm parameters in the presence and absence of H2 O2 . MATERIALS AND METHODS: Semen samples were collected from 30 healthy men in their fourth decade attending Azoury IVF clinic. Spermatozoa, cultured in the presence or absence of 10 µM H2 O2 , were left untreated or treated with increasing concentrations of PRP (2, 5, and 10%). After 24-h incubation, ROS levels were assessed and sperm parameters were evaluated. RESULTS: Our results highlight the harmful effect of H2 O2 on sperm parameters, showing an increase in the percentage of reactive oxygen species (ROS)-positive cells, vacuolization, and sperm DNA fragmentation, and a decrease in progressive and total motility in the H2 O2 -treated group compared to non-stressed spermatozoa. When samples were treated with PRP, an improvement of the studied parameters was noted mainly with 2% PRP, thus regarded as the best concentration to achieve a positive effect on sperm parameters. Indeed, non-stressed and stressed spermatozoa treated with 2% PRP showed a significant increase in progressive and total motility, coupled with a decrease in ROS-positive cells, DNA fragmentation, vacuolization, and dead cells compared to the untreated group. In contrast, no significant difference in cell morphology was found between the two groups. Moreover, 2% PRP treatment enhanced sperm parameters and prevented cell death in H2 O2 -exposed spermatozoa as compared to freshly collected semen. DISCUSSION: We suggest that PRP because of its wide arrays of growth factors included in his alpha granules contributes to the inhibition of ROS through the antioxidant, anti-apoptotic activity. CONCLUSION: Autologous PRP improves the quality of the sperm, more so in the presence of an H2 O2 -induced OS.

Effect of surgical parameters on the biomechanical behaviour of bicondylar total knee endoprostheses - A robot-assisted test method based on a musculoskeletal model.

The complicated interplay of total knee replacement (TKR) positioning and patient-specific soft tissue conditions still causes a considerable number of unsatisfactory outcomes. Therefore, we deployed a robot-assisted test method, in which a six-axis robot moved and loaded a bicondylar cruciate-retaining (CR)-TKR in a virtual lower extremity emulated by a musculoskeletal multibody model. This enabled us to systematically analyse the impact of the posterior cruciate ligament (PCL), tibial slope, and tibial component rotation on TKR function while considering the physical implant components and physiological-like conditions during dynamic motions. The PCL resection yielded a decrease of femoral rollback by 4.5 mm and a reduction of tibiofemoral contact force by 50 N. A reduced tibial slope led to an increase of tibiofemoral contact force by about 170 N and a decrease of femoral rollback up to 1.7 mm. Although a higher tibial slope reduced the contact force, excessive tibial slopes should be avoided to prevent joint instability. Contrary to an external rotation of the tibial component, an internal rotation clearly increased the contact force and lateral femoral rollback. Our data contribute to improved understanding the biomechanics of TKRs and show the capabilities of the robot-assisted test method based on a musculoskeletal multibody model as a preoperative planning tool.

Numerical simulation of the electric field distribution in an electrical stimulation device for scaffolds settled with cartilaginous cells.

Electrical stimulation is a promising approach to enhance cell viability and differentiation. We aim to develop a stimulation device for the investigation and realization of cartilaginous cell engineering. The stimulation setup is capable of applying well-defined electric fields to several scaffolds at the same time. The setup consists of a flat plate with multiple test tubes for the scaffolds. A flexible printed circuit board containing a separate pair of electrodes for each tube is fixed at the bottom of the plate. In this context, numerical simulation using Finite Element Method (FEM) is a valuable tool to gain a better understanding of the electric field distribution in such devices. The thin insulating layer of the flexible printed circuit board allows sufficient field strength to be achieved at moderate input voltages but presents challenges for modelling. In simulations, thin layers would usually require a fine discretization with many degrees of freedom (DOF). This leads to large models, which are expensive regarding memory and computation time. Based on the 'contact impedance' boundary condition available in COMSOL Multiphysics® 5.4, an alternative approach is proposed that can model thin layers in capacitively coupled setups. The resulting electric field distribution in the new stimulation setup is presented and discussed.

Folate/Vitamin B12 Supplementation Combats Oxidative Stress-Associated Carcinogenesis in a Rat Model of Colon Cancer.

Folate and vitamin B12 deficiency is associated with depletion of the major intracellular antioxidant glutathione, and oxidative stress is emerging as an etiological mechanism for colon cancer. Azoxymethane (AOM), a potent carcinogen, induces colon cancer in rats by causing pathophysiological changes and oxidative stress. We investigated the synergistic effect of folate and vitamin B12 supplementation against AOM-induced carcinogenesis and oxidative stress in rat colon. Adult male rats were distributed into four groups: 1) Basal diet only; 2) AOM injection (15 mg/kg once per week in weeks 5 and 6); 3) Folate and vitamin B12 supplemented diet; 4) Folate and B12 diet with AOM injection. After 16 weeks, rats were sacrificed, colon tissue dissected, indicators of oxidative stress were measured, and immunohistochemical and ultrastructural changes were evaluated. AOM-injected rats showed oxidative stress, evident by glutathione depletion, oxidation of cellular proteins, and DNA oxidative damage. AOM increased mucosal levels of antiapoptotic and proapoptotic proteins Bcl2 and Bax and caused ultrastructure changes in colonic cell organelles. Folate and vitamin B12 supplementation decreased the level of oxidative stress and ameliorated the cytotoxic effects of AOM. In this in vivo experimental model of colon cancer, folate and vitamin B12 supplementation combats carcinogen-induced oxidative stress.

Effects of interfacial micromotions on vitality and differentiation of human osteoblasts.

OBJECTIVES: Enhanced micromotions between the implant and surrounding bone can impair osseointegration, resulting in fibrous encapsulation and aseptic loosening of the implant. Since the effect of micromotions on human bone cells is sparsely investigated, an in vitro system, which allows application of micromotions on bone cells and subsequent investigation of bone cell activity, was developed. METHODS: Micromotions ranging from 25 µm to 100 µm were applied as sine or triangle signal with 1 Hz frequency to human osteoblasts seeded on collagen scaffolds. Micromotions were applied for six hours per day over three days. During the micromotions, a static pressure of 527 Pa was exerted on the cells by Ti6Al4V cylinders. Osteoblasts loaded with Ti6Al4V cylinders and unloaded osteoblasts without micromotions served as controls. Subsequently, cell viability, expression of the osteogenic markers collagen type I, alkaline phosphatase, and osteocalcin, as well as gene expression of osteoprotegerin, receptor activator of NF-κB ligand, matrix metalloproteinase-1, and tissue inhibitor of metalloproteinase-1, were investigated. RESULTS: Live and dead cell numbers were higher after 25 µm sine and 50 µm triangle micromotions compared with loaded controls. Collagen type I synthesis was downregulated in respective samples. The metabolic activity and osteocalcin expression level were higher in samples treated with 25 µm micromotions compared with the loaded controls. Furthermore, static loading and micromotions decreased the osteoprotegerin/receptor activator of NF-κB ligand ratio. CONCLUSION: Our system enables investigation of the behaviour of bone cells at the bone-implant interface under shear stress induced by micromotions. We could demonstrate that micromotions applied under static pressure conditions have a significant impact on the activity of osteoblasts seeded on collagen scaffolds. In future studies, higher mechanical stress will be applied and different implant surface structures will be considered.Cite this article: J. Ziebart, S. Fan, C. Schulze, P. W. Kämmerer, R. Bader, A. Jonitz-Heincke. Effects of interfacial micromotions on vitality and differentiation of human osteoblasts. Bone Joint Res 2018;7:187-195. DOI: 10.1302/2046-3758.72.BJR-2017-0228.R1.

Predictors of colonization with Staphylococcus species among patients scheduled for cardiac and orthopedic interventions at tertiary care hospitals in north-eastern Germany-a prevalence screening study.

As methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection in humans are a global challenge. In Mecklenburg and Western Pomerania (Germany) 1,517 patients who underwent surgical interventions were systematically screened for MRSA and MSSA colonization on the day of hospital admission and discharge. Demographic data, risk factors and colonization status of the (i) nose, (ii) throat, (iii) groin, and (iv) thorax or site of surgical intervention were determined. Of the 1,433 patients who were included for further evaluation, 331 (23.1%) were colonized with MSSA, while only 17 (1.2%) were MRSA carriers on the day of hospital admission. A combination of nose, throat and groin swabs returned a detection rate of 98.3% for MSSA/MRSA. Trauma patients had lower prevalence of MRSA/MSSA (OR 0.524, 95% CI: 0.37-0.75; p < 0.001) than patients with intended orthopedic interventions. Males showed significantly higher nasal S. aureus carrier rates than females (odds ratio (OR) = 1.478; 95% CI: 1.14-1.92; p = 0.003). Nasal S. aureus colonization was less frequent among male smokers as compared to non-smokers (chi2 = 16.801; phi = 0.154; p < 0.001). Age, gender and smoking had a significant influence on S. aureus colonization. Combining at least three different swabbing sites should be considered for standard screening procedure to determine S. aureus colonization at patients scheduled for cardiac or orthopedic interventions at tertiary care hospitals.

Cellular fluid shear stress on implant surfaces-establishment of a novel experimental set up.

BACKGROUND: Mechanostimuli of different cells can affect a wide array of cellular and inter-cellular biological processes responsible for dental implant healing. The purpose of this in vitro study was to establish a new test model to create a reproducible flow-induced fluid shear stress (FSS) of osteoblast cells on implant surfaces. METHODS: As FSS effects on osteoblasts are detectable at 10 dyn/cm2, a custom-made flow chamber was created. Computer-aided verification of circulation processes was performed. In order to verify FSS effects, cells were analysed via light and fluorescence microscopy. RESULTS: Utilising computer-aided simulations, the underside of the upper plate was considered to have optimal conditions for cell culturing. At this site, a flow-induced orientation of osteoblast cell clusters and an altered cell morphology with cellular elongation and alteration of actin fibres in the fluid flow direction was detected. CONCLUSIONS: FSS simulation using this novel flow chamber might mimic the peri-implant situation in the phase of loaded implant healing. With this FSS flow chamber, osteoblast cells' sensitivity to FSS was verified in the form of morphological changes and cell re-clustering towards the direction of the flow. Different shear forces can be created simultaneously in a single experiment.

Devitalisation of human cartilage by high hydrostatic pressure treatment: Subsequent cultivation of chondrocytes and mesenchymal stem cells on the devitalised tissue.

The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair.

Genome wide array-CGH and qPCR analysis for the identification of genome defects in Williams' syndrome patients in Saudi Arabia.

BACKGROUND: Williams-Beuren Syndrome (WBS) is a rare neurodevelopmental disorder characterized by dysmorphic features, cardiovascular defects, cognitive deficits and developmental delay. WBS is caused by a segmental aneuploidy of chromosome 7 due to heterozygous deletion of contiguous genes at the long arm of chromosome 7q11.23. We aimed to apply array-CGH technique for the detection of copy number variants in suspected WBS patients and to determine the size of the deleted segment at chromosome 7q11.23 in correlation with the phenotype. The study included 24 patients referred to the CEGMR with the provisional diagnosis of WBS and 8 parents. The patients were subjected to conventional Cytogenetic (G-banding) analysis, Molecular Cytogenetic (Fluorescent In-Situ Hybridization), array-based Comparative Genomic Hybridization (array-CGH) and quantitative Real time PCR (qPCR) Techniques. RESULTS: No deletions were detected by Karyotyping, however, one patient showed unbalanced translocation between chromosome 18 and 19, the karyotype was 45,XX, der(19) t(18;19)(q11.1;p13.3)-18. FISH technique could detect microdeletion in chromosome 7q11.23 in 10/24 patients. Array-CGH and qPCR confirmed the deletion in all samples, and could detect duplication of 7q11.23 in three patients and two parents. Furthermore, the size of the deletion could be detected accurately by both array-CGH and qPCR techniques. Three patients not showing the 7q11.23 deletion were diagnosed by array-CGH to have deletion in chr9p13.1-p11.2, chr18p11.32-p11.21 and chr1p36.13. CONCLUSION: Both FISH and array-CGH are reliable methods for the diagnosis of WBS; however, array-CGH has the advantage of detection of genome deletions/ duplications that cannot otherwise be detected by conventional cytogenetic techniques. Array-CGH and qPCR are useful for detection of deletion sizes and prediction of the interrupted genes and their impact on the disease phenotype. Further investigations are needed for studying the impact of deletion sizes and function of the deleted genes on chromosome 7q11.23. TRIAL REGISTRATION: ISRCTN ISRCTN73824458. MOCY-D-16-00041R1. Registered 28 September 2014. Retrospectively registered.

[Perioperative Management in Microsurgery - Consensus Statement of the German Speaking Society for Microsurgery of Peripheral Nerves and Vessels]. / Perioperatives Management in der Mikrochirurgie - Konsensus-Statement der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie der peripheren Nerven und Gefäße.

Perioperative management of microsurgery is not well standardised. Due to a lack of evidence, different regimes are established in different microsurgical centres. However, trends towards less aggressive perioperative interventions can be identified in recent years, since treatment algorithms without systematic evidence are being progressively abandoned. The available evidence on perioperative issues, such as temperature control, fluid resuscitation, blood transfusions, application of vasodilators or - pressors, as well as anticoagulants, were discussed during the consensus conference on perioperative management at the annual meeting of the German Speaking Society for Microsurgery of Peripheral Nerves and Vessels. Common basic standards were identified and a consensus was reached that is described in the following manuscript.

Potential infection control risks associated with roaming healthcare industry representatives.

BACKGROUND: Healthcare industry representatives (HCIR) visit multiple hospitals every day. Most enter hygiene sensitive areas and work in close proximity to caregivers and patients. OBJECTIVE: The objective of the present study was to evaluate the HCIRs' current status in hygiene training and vaccination. METHODS: An anonymous walking intercept study was used based on questionnaires to evaluate industry representatives in comparison to physicians and nurses (n = 311 participants, participation rate 30.2%) after their visit to the MEDICA Congress. The valid participants consisted of HCIR (n = 208), hospital nurses (n = 49) and physicians (n = 41). A total of 82.2% (n = 171) HCIR worked in varying hospitals. RESULTS: They frequently request access to hygiene and data-privacy sensitive areas: Among them 51.9% (n = 108) accessed the outpatient clinic, 41.8% (n = 87) the operating room (OR), 33.7% (n = 70) the central supply and sterilisation department (CSSD), and 32.7% (n = 68) the intensive care unit. HCIR requesting access to hygiene sensitive areas showed the lowest scores in hygiene training and a significantly lower Hepatitis B vaccination status, i.e. 37.5% compared to 70.7% for physicians and 53.1% for nurses. DISCUSSION: Status of HCIR hygiene training was inadequate - as was vaccination and contamination control. Therefore, HCIR are exposed to increased infection risk and may unknowingly act as infection vector between different hospitals.

[Quality of Outcome after Primary Total Hip Replacement at a Maximum Care Hospital in Relation to Preoperative Influencing Factors]. / Ergebnisqualität nach Hüftendoprothesen-Erstimplantation an einem Krankenhaus der Maximalversorgung in Bezug auf präoperative Einflussfaktoren.

BACKGROUND: As the need for joint replacements will continue to rise, the outcome of primary total hip replacement (THR) must be improved and stabilised at a high level. In this study, we investigated whether pre-operative risk factors, such as gender, age and body weight at the time of the surgery or a restricted physical status (ASA-Status > 2 or Kellgren and Lawrence grade > 2) have a negative influence on the post-operative results or on patient satisfaction. MATERIAL AND METHODS: Retrospective data collection and a prospective interview were performed with 486 patients who underwent primary total hip replacement between January 2007 and December 2010 in our hospital. The patients' satisfaction and quality of life were surveyed with the WOMAC-Score, SF-36 and EuroQol-5. Differences between more than two independent spot tests were tested with the non-parametric Kruskal-Wallis test. Differences between two independent spot tests were tested with the non-parametric Mann-Whitney U test. The frequencies were reported and odds ratios calculated. The confidence interval was set at 95 %. The level of significance was p < 0.05. RESULTS: The average WOMAC-Score was 77.1 and the total score of the SF-36 was 66.9 points. The patients declared an average EuroQol Index of 0.81. Our data show that the patients' gender did not influence the duration of surgery or the scores. However, female patients tended to exhibit more postoperative complications. However, increased patient age at the time of surgery was associated with an increased OR for duration of surgery, length of stay and risk of complications. Patients who had a normal body weight at time of the surgery showed better peri- and post-operative results. We showed that the preoperative estimated Kellgren and Lawrence grade had a significant influence on the duration of surgery. The ASA classification influenced the duration of surgery as well the length of stay and the rate of complications. CONCLUSION: The quality of results after primary THR depends on preoperative factors. Existing comorbidities have a significant influence on the duration of surgery and therefore on the perioperative rate of complications and the postoperative outcome. Despite improvements in the functional and subjective outcome after primary THR, an adverse preoperative symptomatic status is associated with less favourable postoperative results.