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Thomas Ferbert, Christina Münch, Sebastian Findeisen, William Pauly, Matthias Miska, Tobias Grossner, Michael C Tanner, Gerhard Schmidmaier, Lars Helbig Clinic for Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Heidelberg, D-69118, GermanyCorrespondence: Lars Helbig, Clinic for Trauma and Reconstructive Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg, D-69118, Germany, Tel +496221/5635371, Fax +496221/5626300, Email lars.helbig@med.uni-heidelberg.dePurpose: A central aspect of the treatment of non-unions is the filling of bone defects. The quantity of available autologous bone for this purpose is limited. Alternatively, or additionally, bone substitutes may be used. The aim of this retrospective, single-center study including 404 non-unions in 393 patients is to investigate the effect of tricalcium phosphate (TCP) on the healing of non-unions. Furthermore, the influence of gender, age, smoking status, comorbidities, type of surgical procedure, presence of infection, and length of treatment was investigated.Methods: We evaluated three groups of patients. Group 1 received TCP + BG, group 2 received BG alone and group 3 received no augmentation. Bone stability was assessed 1 and 2 years after non-union revision surgery through analysis of radiographs using the Lane Sandhu Score. Scores ≥ 3 were rated as stable Other influencing factors were collected from the electronic medical record.Results: In 224 non-unions, bone defects were filled with autologous bone and TCP (TCP+BG). In 137 non-unions, bone defects were filled with autologous bone (BG), and in 43 non-unions presenting non-relevant defects, neither autologous bone nor TCP were used (NBG). After 2 years, 72.7% of the TCP+BG patients, 90.1% of the BG patients and 84.4% of the NBG patients achieved a consolidation score ≥ 3. Advanced age, presence of comorbidities and longer treatment period had a significantly negative effect on consolidation 1 year after surgery. Longer treatment periods also showed a negative significant effect after 2 years. It is notable that larger defects, mainly treated with the combination of autologous bone and TCP, showed similar healing rates to that of smaller defects after 2 years.Conclusion: The combination of TCP and autologous bone-grafts shows good results in the reconstruction of complicated bone-defects, but patience is required since the healing period exceeds 1 year in most patients.Keywords: non-unions, bone substitute, Lane Sandhu Score, tricalcium phosphate

Michael C Tanner,1 Raban Arved Heller,1– 3 Andreas Grimm,1 Stefan Zimmermann,4 Maximilian Pilz,5 Louisa Jurytko,1 Matthias Miska,1 Lars Helbig,1 Gerhard Schmidmaier,1 Patrick Haubruck1,6 1HTRG – Heidelberg Trauma Research Group, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, Heidelberg, D-69118, Germany; 2Institute for Experimental Endocrinology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt Universität Zu Berlin, Berlin Institute of Health, Berlin, D-13353, Germany; 3Department of General Practice and Health Services Research, Heidelberg University Hospital, Heidelberg, D-69120, Germany; 4Division Bacteriology, Department of Infectious Diseases, Heidelberg University Hospital, Heidelberg, D-69120, Germany; 5Institute of Medical Biometry and Informatics, Heidelberg University Hospital, Heidelberg, D-69120, Germany; 6Raymond Purves Bone and Joint Research Laboratory, Institute of Bone and Joint Research, Kolling Institute, Royal North Shore Hospital, University of Sydney, St. Leonards, New South Wales, A-2068, AustraliaCorrespondence: Patrick HaubruckRaymond Purves Bone and Joint Research Laboratory, Institute of Bone and Joint Research, Kolling Institute, Royal North Shore Hospital, University of Sydney, St Leonards, NSW, A-2068, AustraliaTel +61 (0) 437320789Email patrick.haubruck@sydney.edu.auBackground: Occult infections (OI) lack typical inflammatory signs, making them challenging to diagnose. Uncertainty remains regarding OI’s influence on the outcome of autologous bone grafting (ABG), and evidence-based recommendations regarding an appropriate course of action are missing. Thus, we sought to determine the incidence of an OI in patients receiving ABG, evaluate whether it influences the outcome of ABG and whether associated risk factors have a further negative influence.Methods: This study was designed as a large size single-center case-control study investigating patients treated between 01/01/2010 and 31/12/2016 with a minimum follow-up of 12 months. Patients ≥ 18 years presenting with a recalcitrant non-union of the lower limb receiving surgical bone reconstruction, including bone grafting, were included. A total of 625 patients were recruited, and 509 patients included in the current study. All patients received surgical non-union therapy based on the “diamond concept” including bone reconstruction using ABG. Additionally, multiple tissue samples were harvested and microbiologically analyzed. Tissue samples were microbiologically evaluated regarding an OI. Bone healing was analyzed using clinical and radiological parameters, patient characteristics and comorbidities investigated and ultimately results correlated.Results: Forty-six out of 509 cases with OI resulted in an incidence of 9.04%. Overall consolidation time was increased by 15.08 weeks and radiological outcome slightly impaired (79.38% vs 71.42%), differences were at a non-significant extent. Diabetes mellitus had a significant negative influence on consolidation time (p=0.0313), while age (p=0.0339), smoking status (p=0.0337), diabetes mellitus (p=0.0400) and increased BMI (p=0.0315) showed a significant negative influence on the outcome of bone grafting.Conclusion: Surgeons treating recalcitrant non-unions should be aware that an OI is common. If an OI is diagnosed subsequent to ABG the majority of patients does not need immediate revision surgery. However, special attention needs to be paid to high-risk patients.Keywords: infection, bone healing, bone regeneration, non-union, bone infection

Michael C Tanner, Saskia Hagelskamp, Wasilios Vlachopoulos, Matthias Miska, Sebastian Findeisen, Andreas Grimm, Gerhard Schmidmaier, Patrick Haubruck Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, Heidelberg, GermanyCorrespondence: Michael C TannerCenter for Orthopedics, Trauma Surgery and Spinal Cord Injury, Trauma and Reconstructive Surgery, Heidelberg University Hospital, Schlierbacher Landstrasse 200a, Heidelberg D-69118, GermanyTel +49-6221-5635987Fax +49-6221-5626300Email michael.tanner@med.uni-heidelberg.deBackground: Patients > 60 years suffering from non-unions are often unable to perform activities of daily living and often become dependent on nursing care. Evidence regarding treatment options and outcome is nonexistent. This study sought to determine the clinical effectiveness and safety of one- or two-step non-union therapy in elderly patients.Methods: This study was a single-site retrospective database analysis of older adults with long bone non-unions treated via “diamond concept”. All medical records of patients receiving surgical treatment of non-unions between 01/01/2010 and 31/12/2016 were reviewed. Clinical and radiological outcome subsequent to non-union therapy were evaluated.Results: A total of 76 patients (37 patients were treated with one-step and 39 patients with Masquelet therapy) suffering from a non-union older than 60 years treated between 01/01/2010 and 31/12/2016 in our institution were included into the current study. Bone consolidation was achieved in 91.9% after one-step and 76.9% after the Masquelet therapy. Analysis of age as a risk factor in the outcome of non-union therapy revealed no significant differences in patients treated with the one-step procedure according to the “diamond concept”. On the contrary, age had a significant negative influence on the outcome of the Masquelet therapy (p = 0.027).Conclusion: Non-union therapy according to the “diamond concept” is an effective and reliable treatment option in elderly patients. According to findings of the current study, older adults suffering from an infected non-union benefit from a two-stage procedure, whereas in patients suffering from a non-infected non-union, a one-step surgical treatment is beneficial.Keywords: fracture healing, Masquelet-procedure, non-union therapy, pseudarthrosis

Background Given the steady increase of emergency department (ED) visits related to opioid overdoses, this study aims to determine the design and usability of an ED-centered mHealth patient-to-peer referral prototype tool that allows patients to refer peers to comprehensive HIV/HCV and opioid misuse prevention services. Methods Two iterative focus group discussion (FDG) sessions and one use-case session were conducted. Eligible participants who were ≥18 years, had a history of injection drug use (IDU), and had utilized the ED in the past year were recruited through the distribution of flyers at the study institution, including the study ED. Human-centered design process was completed by using participant feedback on perceived utility, usability/accessibility, tool design, and clarity/readability to fine-tune prototype version and drive subsequent discussion sessions. Results Sixteen consented individuals participated in at least one of the sessions. Feedback revealed that participants favored the inclusion of the webpage link on the referral card as means to bypass QR code if needed, more descriptions highlighting the exact services offered, and the fact that no personal information was required to complete the referral process. The prototype underwent several adjustments between user-centered FDG sessions, which ultimately ended in including features such as an online webpage with educational videos, SMS text-message communication system, and QR code usage into the final patient-to-peer referral tool prototype. Conclusion The findings of this study suggest a human-centered designed patient-to-peer referral tool could be a feasible approach to linking community members at risk of IDU to HIV/HCV and opioid use-related preventive services from ED patients.

In this article, a machine learning aided electronic warfare (EW) system is presented and the simulation results are discussed. The developed EW system uses an automatic decision tree generator to create engagement protocol and a fuzzy logic model to quantify threat levels. A long-short term memory (LSTM) neural network was also trained to predict the next signal set of multifunction radars. The simulation results demonstrate the effectiveness of the developed EW system’s ability to engage multiple multifunction radars.

Binary expression systems like the LexA-LexAop system provide a powerful experimental tool kit to study gene and tissue function in developmental biology, neurobiology, and physiology. However, the number of well-defined LexA enhancer trap insertions remains limited. In this study, we present the molecular characterization and initial tissue expression analysis of nearly 100 novel StanEx LexA enhancer traps, derived from the StanEx1 index line. This includes 76 insertions into novel, distinct gene loci not previously associated with enhancer traps or targeted LexA constructs. Additionally, our studies revealed evidence for selective transposase-dependent replacement of a previously-undetected KP element on chromosome III within the StanEx1 genetic background during hybrid dysgenesis, suggesting a molecular basis for the over-representation of LexA insertions at the NK7.1 locus in our screen. Production and characterization of novel fly lines were performed by students and teachers in experiment-based genetics classes within a geographically diverse network of public and independent high schools. Thus, unique partnerships between secondary schools and university-based programs have produced and characterized novel genetic and molecular resources in Drosophila for open-source distribution, and provide paradigms for development of science education through experience-based pedagogy.

Cancer cell fusion was suggested as a mechanism of metastasis about a century ago. Since then, many additional modes of material transfer (i.e., tunneling nanotubes, and exosomes) to generate cell hybrids have been identified. However, studies documenting spontaneous tumor hybrid formation in vivo as a mechanism that enables metastasis are still lacking. Here, we tested whether spontaneous hybrid formation in vivo contributes to bona fide metastatic tumors. We first used single cell RNASeq to analyze the gene expression profile of spontaneously formed cancer cell-stromal hybrids, and results revealed that hybrids exhibit a clustering pattern that is distinct from either parental cell and suggestive of substantial diversity of individual hybrids. Despite the newly gained diversity, hybrids can retain expression of critical genes of each parental cell. To assess the biological impact of cancer cell hybrids in vivo, we transfected murine mammary tumor cells, isolated from FVB/N-Tg(MMTV-PyVT)634Mul/J mice (PyVT) with Cre recombinase prior to injection to the murine fat pad of FVB.129S6(B6)-Gt(ROSA)26Sortm1(Luc)Kael/J mice such that luciferase expression is induced with hybrid formation; luciferase expression was tracked for up to four months. We observed that hybrid formation occurs spontaneously in vivo and that a significantly higher number of hybrids reside in metastases compared to the primary tumor, supporting the possibility that hybrids can emerge from the primary tumor and proliferate to help create a new tumor at a distant site. Additional studies are now warranted to delineate the mechanisms of cancer cell hybrid transit to metastases since drugs to inhibit hybrid formation might prevent metastatic spread.

Background: The treatment of large-sized bone defects remains a major challenge in trauma and orthopaedic surgery. Although there are many treatment options, there is still no clear guidance on surgical management, and the influence of defect size on radiological and clinical outcome remains unclear due to the small number of affected patients. The aim of the present study was to determine the influence of defect size on the outcome of atrophic and infected nonunions of the tibia or the femur based on the diamond concept in order to provide recommendations for treatment guidance., Patients and Methods: All medical records, surgical reports, laboratory data and radiological images of patients treated surgically for atrophic or infected nonunions of the lower limbs (femur or tibia) between 1 January 2010 and 31 December 2020 were examined. Patients with proximal, diaphyseal or distal nonunions of the femur or tibia who were surgically treated at our institution according to the "diamond concept" and attended our standardised follow-up program were included in a database. Surgical treatment was performed as a one- or two-step procedure, depending on the type of nonunion. Patients with a segmental bone defect ≥5 cm were matched with patients suffering a bone defect <5 cm based on five established criteria. According to our inclusion and exclusion criteria, 70 patients with a bone defect ≥5 cm were suitable for analysis. Two groups were formed by matching: the study group (bone defect ≥5 cm; n = 39) and control group (bone defect <5 cm; n = 39). The study was approved by the local ethics committee (S-262/2017)., Results: The mean defect size was 7.13 cm in the study and 2.09 cm in the control group. The chi-square test showed equal consolidation rates between the groups (SG: 53.8%; CG: 66.7%). However, the Kaplan-Meier curve and log-rank test showed a significant difference regarding the mean duration until consolidation was achieved, with an average of 15.95 months in the study and 9.24 months in the control group (α = 0.05, p = 0.001). Linear regression showed a significant increase in consolidation duration with increasing defect size (R 2 = 0.121, p = 0.021). Logistic regression modelling showed a significant negative correlation between consolidation rate and revision performance, as well as an increasing number of revisions, prior surgeries and total number of surgeries performed on the limb. Clinical outcomes showed equal full weight bearing of the lower extremity after 5.54 months in the study vs. 4.86 months in the control group ( p = 0.267)., Conclusion: Surprisingly, defect size does not seem to have a significant effect on the consolidation rate and should not be seen as a risk factor. However, for the treatment of large-sized nonunions, the follow-up period should be prolonged up to 24 months, due to the extended time until consolidation will be achieved. This period should also pass before a premature revision with new bone augmentation is performed. In addition, it should be kept in mind that as the number of previous surgeries and revisions increases, the prospects for consolidation decrease and a change in therapeutic approach may be required.

Objective: To determine if left ventricular systolic function on echocardiography, systemic blood pressure, and electrocardiography change with a clinically accepted intravenous (IV) diltiazem constant rate infusion (CRI) compared to a control., Animals: 10 healthy client-owned adult dogs., Procedures: Prospective, masked, crossover study from May 27, 2021, to August 22, 2021. Dogs were randomized to receive diltiazem (loading dose of 240 μg/kg, IV followed by a CRI of 6 μg/kg/min for 300 minutes) or the same volume of 5% dextrose in water (D5W) administered IV followed by the opposite intervention after a 7-day washout. Blood pressure was monitored during each CRI, and echocardiographic and electrocardiographic studies were performed immediately before the CRI and during the last hour of the CRI., Results: Postdiltiazem systolic time interval (STI) (median, 0.30; range, 0.16 to 0.34) was significantly lower than post-D5W STI (median, 0.32; range, 0.22 to 0.40; P = .046). All other echocardiographic parameters did not differ significantly between each of the groups after receiving diltiazem or D5W. Systemic blood pressure did not change significantly with either diltiazem (P = .450) or D5W (P = .940), and none of the dogs became hypotensive at any point in the study. Expectedly, negative dromotropy was observed with diltiazem., Clinical Relevance: A significant decrease in left ventricular systolic function was not appreciated in healthy dogs receiving diltiazem at a clinically accepted intravenous infusion rate at this dosing regimen. Further studies are needed in dogs with cardiac disease.

Background: Acute kidney injury (AKI) in dogs has a high case fatality rate. Diltiazem might improve renal function, but effect of intravenous infusion has not been adequately studied in dogs., Hypothesis/objectives: To determine if an intravenous infusion of diltiazem improves renal function through changes in glomerular filtration rate (GFR), fractional excretion of sodium (FENa), and urine output (UOP) in healthy dogs., Animals: Ten healthy adult dogs., Methods: Prospective, unmasked, crossover study. Dogs were randomized to receive diltiazem (loading dose of 240 μg/kg followed by 6 μg/kg/min for 300 min) or the same volume of 5% dextrose in water (D5W). The opposite treatment was given after a 7-day washout period. GFR and FENa were obtained at baseline and after infusion. UOP was measured starting 1 hour before diltiazem administration., Results: GFR did not significantly increase from baseline with diltiazem (before diltiazem median = 2.371 mL/min/kg, range = 1.605-4.359; after diltiazem median = 2.305 mL/min/kg, range = 1.629-4.387; median difference = 0.080 mL/min/kg, 95% confidence interval [CI] = -0.417 to 0.757; P = .85), and there was no difference in D5W GFR before and after diltiazem (median = 2.389 mL/min/kg, range = 1.600-3.557; median difference = 0.036 mL/min/kg, 95% CI = -0.241 to 1.112; P = .69). FENa did not increase from baseline after administration of diltiazem (median difference = 0%, 95% CI = -0.1 to 0.1; P = .81), and there was no difference in D5W FENa (median difference = 0.1%, 95% CI = -0.1 to 0.2; P = .26). UOP did not increase with diltiazem (P = .06)., Conclusion and Clinical Importance: Intravenous administration of diltiazem does not improve markers of renal function in healthy dogs. Further studies are needed in dogs with AKI., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A five-month-old, intact female Domestic Shorthair cat presented to the Kansas State Veterinary Health Center for evaluation of a murmur and exercise intolerance. Physical exam revealed a grade V/VI right, parasternal, holosystolic murmur. On echocardiogram, there was an abnormality in the membranous interventricular septum and tricuspid valve, allowing blood to shunt from the left ventricle to the right atrium. This lesion is consistent with an infravalvular Gerbode defect. The Gerbode defect is a rare, left ventricle-to-right atrial shunt that can be congenital or acquired, and in cats, has only been reported once. At the time of submission, the patient is alive and is maintaining a good quality of life., Competing Interests: Conflicts of Interest Statement The authors report no actual or potential conflicts of interest relative to this article., (Published by Elsevier B.V.)

Background: Implant-associated infections (IAI) remain a challenging complication in osteosynthesis. There is no consensus or clear evidence whether titanium offers a relevant clinical benefit over stainless steel., Purpose: In this systematic review, we sought to determine whether the implant properties of titanium reduce the susceptibility to IAI compared to stainless steel in fracture management., Methods: A systematic literature search in German and English was performed using specific search terms and limits. Studies published between 1995 and 1st June 2020 in the Cochrane library, MEDLINE and Web of Science databases were included. Only clinical studies comparing titanium and stainless steel implants regarding the susceptibility to infections were selected for detailed review., Results: Five studies out of 384 papers were identified and reviewed. From the studies meeting inclusion criteria one study was a systematic review, two studies were randomized controlled studies (RCT) and two studies were of retrospective comparative nature of level IV evidence., Conclusion: Our results show that currently, no proven advantage for titanium implants in respect to IAI can be seen in contemporary literature. Implants preserving periosteal blood-flow and minimising soft-tissue trauma show statistically significant benefits in reducing the incidence of IAI. Clinical studies providing reliable evidence regarding the influence of titanium implants on IAI and investigating the susceptibility of titanium to infection are necessary., (© 2021. The Author(s).)

Two-step Masquelet-technique established a new procedure in the treatment of osseous defects, addressing prerequisites postulated by the "diamond concept". Increase in blood perfusion and growth factors are enhanced by the "Masquelet-membrane". To describe this, we measured serum levels of Vascular Endothelial Growth Factor (VEGF) of patients with atrophic non-unions of long bones undergoing Masquelet-technique. From over 500 non-union patients undergoing Masquelet-technique with prospective follow-up we randomly selected 30 patients. 23 were included, 7 lost to follow-up or excluded because of incomplete data. Serum was drawn at specified intervals before and after surgery. Patients were followed for at least 6 months after step 2. Classification into both groups was performed according to radiological results and clinical outcome 6 months after step 2. Concentration of VEGF in patients' serum was performed via ELISA. 14 achieved osseous consolidation (responder group), 9 cases did not (non-responder). Responders showed a significant increase of serum-VEGF in the first and second week when compared to the preoperative values of step 1. Non-responders showed a significant increase of VEGF in the second week after Steps 1 and 2. Comparison of groups showed significantly higher increase of serum-VEGF week2 after step 1 and preoperative to step 2 for responders. Results show one possibility of illustrating therapeutic progress by monitoring growth factors and possibly allowing prognostic conclusions thereof. This might lead to a more targeted treatment protocol.

Dry reagent strip evaluation of urine is a standard screening and diagnostic test used to assess overall health and help detect or rule out specific disease conditions. A commercial at-home urinalysis reagent strip kit using a smartphone app to evaluate free-catch urine is being marketed directly to dog and cat owners. We compared agreement between simultaneous urinalysis using the commercial kit and standard reference methods in 48 canine urines submitted to our referral laboratory. Agreement was defined by analyte based on clinical impact. Sensitivity, specificity, and Cohen's kappa evaluated categorical data, and a paired t test was used for continuous variables (significance P < .05). The commercial kit had ≥1 disagreement with the reference method per sample and produced results if the test strip was absent or reversed. Specific gravity and pH concurred with the reference method in only 31% ( P < .011) and 27% ( P < .001) of cases, respectively. The sensitivity was low for all analytes except ketones, which had 77% false positives. False-positive nitrites and leukocytes were also frequent (36 and 19%, respectively). False negatives for blood (27%), nitrites (38%), and protein (54%) were common. This kit is inaccurate; its use for clinical decisions is not recommended.

Following publication of the original article [1], the author reported that the given name and family name of all authors were swapped.

Background: There is an increasing need for objective and validated educational concepts. This holds especially true for surgical procedures like chest tube insertion (CTI). Thus, we developed an instrument for objectification of learning successes: the assessment scale based on Objective Structured Assessment of Technical Skill (OSATS) for chest tube insertion, which is evaluated in this study. Primary endpoint was the evaluation of intermethod reliability (IM). Secondary endpoints are 'indirect' interrater reliability (IR) and construct validity of the scale (CV)., Methods: Every participant (N = 59) performed a CTI on a porcine thorax. Participants received three ratings (one 'direct' on site, two 'indirect' via video rating). IM compares 'direct' with 'indirect' ratings. IR was assessed between 'indirect' ratings. CV was investigated by subgroup analysis based on prior experience in CTI for 'direct' and 'indirect' rating., Results: We included 59 medical students to our study. IM showed moderate conformity ('direct' vs. 'indirect 1' ICC = 0.735, 95% CI: 0.554-0.843; 'direct' vs. 'indirect 2' ICC = 0.722, 95% CI 0.533-0.835) and good conformity between 'direct' vs. 'average indirect' rating (ICC = 0.764, 95% CI: 0.6-0.86). IR showed good conformity (ICC = 0.84, 95% CI: 0.707-0.91). CV was proven between subgroups in 'direct' (p = 0.037) and 'indirect' rating (p = 0.013)., Conclusion: Results for IM suggest equivalence for 'direct' and 'indirect' ratings, while both IR and CV was demonstrated in both rating methods. Thus, the assessment scale seems a reliable method for rating trainees' performances 'directly' as well as 'indirectly'. It may help to objectify and facilitate the assessment of training of chest tube insertion.

Background: Substantial evidence exists demonstrating the individual effectiveness of both rhBMP-2 and -7 in the treatment of nonunions, data comparing the clinical effectiveness of adjunct rhBMP-2 and -7 remains scarce. Therefore, we examined our large single-center case series to compare the clinical effectiveness of both rhBMP-2 and -7 in non-union therapy aiming to answer: - Does a certain type of BMP have an advantageous effect on radiological outcome of applied lower limb non-union therapy? - Does application of a certain type of BMP have an advantageous effect on radiological outcome of infected lower limb nonunions? - Are there any additional risk factors associated with inferior outcome in context with an adjunct BMP treatment?, Hypothesis: Both BMPs have the same effect on the radiological outcome of surgically treated lower limb nonunions., Patients and Methods: Single-center retrospective database analysis of a case series of patients with lower limb long bone nonunions receiving either a one- or two-stage (Masquelet-) procedure based on the "diamond concept" with application of rhBMP-2 or -7. The "diamond concept" summarizes core factors that need to be present to achieve bone healing. In particular, these factors relate to the optimization of the mechanical (stability) and biological environment (sufficient osteogenic and angiogenic cells, osteoconductive scaffolds and growth factors). All medical data from patients that received surgical treatment between 01/01/2010 and 31/12/2016 were assessed. In total, 356 patients were treated with BMPs and 156 patients 18 years or older with non-union of their tibia or femur having a follow-up of at least 1 year were included. Consolidation in context with type of rhBMP was compared and the influence of relevant risk factors assessed., Results: Consolidation rate was significantly higher in patients treated with rhBMP-2 (rhBMP-2: 42/46 (91%) vs. rhBMP-7: 64/110 (58%); p<0.001). In particular, application of rhBMP-2 increased the likelihood of consolidation for tibial nonunions (OR 32.744; 95%CI: 2.909-368.544; p=0.005) and when used in two-stage therapy (OR 12.095; 95% CI: 2.744-53.314; p=0.001). Furthermore, regression modeling revealed a higher correlation between application of rhBMP-2 and osseous consolidation in infected nonunions (OR 61.062; 95% CI: 2.208-1688.475; p=0.015) than in aseptic nonunions (OR 4.787; 95% CI: 1.321-17.351; p=0.017). Risk factors negatively influencing the outcome of non-union treatment in context with rhBMPs were identified as active smoking (OR 0.357; 95% CI: 0.138-0.927; p=0.024), atrophic nonunion (OR 0.23; 95% CI: 0.061-0.869; p=0.030), higher BMI (OR 0.919; 95% CI: 0.846-0.998; p=0.046) and a larger defect size (OR 0.877; 95% CI: 0.784-0.98; p=0.021)., Discussion: Patients who received rhBMP-2 for the treatment of tibial nonunions and as part of the two-stage treatment had a significantly higher rate of healing compared to patients treated with rhBMP-7 regardless of infection., Level of Evidence: III, retrospective case-control study., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Chest tube insertion is a standard intervention for management of various injuries of the thorax. Efficient clinical training of this and similar bed-side procedures is equally demanded and improvable. Here, we propose a nouveau means of assessment and feedback using an Objective Structured Assessment of Technical Skills (OSATS) tool. The modified OSATS for chest drain insertion is evaluated in a pilot trial focusing on chest drain insertion. Methods: Participants in the pilot trial were medical students (3 rd -6 th year of studies, n=9), junior residents (1 st -3 rd post-graduate year, n=12), senior residents (4 th -6 th post-graduate year, n=14), and attending surgeons (n=6) from Heidelberg University. Chest drain insertions on a cadaveric porcine model were rated by experts with the modified OSATS score. Participants' performances were videotaped and subsequently rated by two remote experts (video rating). Primary aim was to assess criterion validity of the OSATS to distinguish experience levels. Results: Kruskal-Wallis test showed significant differences between means of scores between four groups stratified by previous experience in chest tube insertion (level 0: 22.1±3.2 vs. level 1: 26.8±2.8 vs. level 2: 35.4±2.2 vs. level 3: 41.0±2.0; p=0.002; p 1,3 =0.049, p 0,3 =0.005). However, if groups were stratified by formal professional level, no statistically significant distinction could be made using OSATS. Hence, the OSATS tool showed criterion validity for differentiation between experience levels. Conclusion: In the pilot study, the modified OSATS for chest tube insertion was apt to standardize expert rating and could be used to measure skill and to depict different experience levels. The OSATS will help facilitate training and assessment of chest drain insertion and could therefore improve surgical training for trauma situations. According to our data, the OSATS might be integrated into modern curricula.

The current study investigates if contrast-enhanced ultrasound (CEUS) or cytokine expression analysis (CEA) evaluating vascularization are capable of predicting the outcome of non-union therapy. Patients with tibial non-unions were surgically treated and participated in our follow-up program including perioperative collection of blood as well as CEUS analysis. Two groups were formed: Responders in group 1 (G1, N = 8) and Non-Responders in group 2 (G2, N = 5). Serum cytokine expression and local microperfusion were compared and correlated to the radiologic outcome. Evaluation of TNF-α expression revealed significantly lower values prior to first surgery in G1 (G1: 9.66 ± 0.96 pg/mL versus G2: 12.63 ± 1.2 pg/mL; p = 0.045); whereas after treatment both CEA and CEUS indicated a higher potential for angiogenesis in Responders. Logistic regression modelling revealed the highest predictive power regarding eventual osseous consolidation for the combination of both CEUS and serum CEA. The results provide first evidence regarding a link between changes in the serum expression of distinct pro-angiogenic cytokines and alterations in the local microperfusion assessed via both non-invasive and radiation-free diagnostic modalities. In addition, a combination of CEUS and CEA is a promising novel tool in early prediction of the outcome of non-union therapy.

Background: Transitioning activities that do not require clinical judgment from pharmacists to pharmacy technicians has been endorsed as a strategy to increase patient access to clinical pharmacy services. One role becoming increasingly common is using pharmacy technicians to collect the medication history within medication reconciliation processes., Objective: To assess the ability of pharmacy technicians to gather a complete and accurate medication history during the inpatient admission process at a regional medical center., Methods: Prospective study of unscheduled inpatient admissions at Salem Hospital. Patients where the initial information source was patient or caregiver interview, had two medication histories collected - one by a pharmacy technician through usual care processes and one by a student pharmacist with pharmacist oversight. Medication histories were then compared and a percent accuracy ranging from 0 - 100% was calculated for each of the pharmacy technician-collected histories., Results: A total of 101 patients were included from January 19 to March 6, 2016. Patients were on average 65 ± 19 years of age and taking 7 ± 6 medications at admission. The accuracy of the technician collected histories was 92.9 ± 14.2%. Accuracy was not impacted by age, number of medications, or admitting shift (all p > 0.05)., Conclusions: Pharmacy technicians can collect complete and accurate medication histories. Results add to the growing body of literature supporting an expanded role for pharmacy technicians in medication reconciliation processes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Treatment of non-union remains challenging and often necessitates augmentation of the resulting defect with an autologous bone graft (ABG). ABG is limited in quantity and its harvesting incurs an additional surgical intervention leaving the risk for associated complications and morbidities. Therefore, artificial bone graft substitutes that might replace autologous bone are needed. S53P4-type bioactive glass (BaG) is a promising material which might be used as bone graft substitute due to its osteostimulative, conductive and antimicrobial properties. In this study, we plan to examine the clinical effectiveness of BaG as a bone graft substitute in Masquelet therapy in comparison with present standard Masquelet therapy using an ABG with tricalciumphosphate to fill the bone defect., Methods/design: This randomized controlled, clinical non-inferiority trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University. Patients who suffer from tibial or femoral non-unions with a segmental bone defect of 2-5 cm and who are receiving Masquelet treatment will be included in the study. The resulting bone defect will either be filled with autologous bone and tricalciumphosphate (control group, N = 25) or BaG (S53P4) (study group, N = 25). Subsequent to operative therapy, all patients will receive the same standardized follow-up procedures. The primary endpoint of the study is union achieved 1year after surgery., Discussion: The results from the current study will help evaluate the clinical effectiveness of this promising biomaterial in non-union therapy. In addition, this randomized trial will help to identify potential benefits and limitations regarding the use of BaG in Masquelet therapy. Data from the study will increase the knowledge about BaG as a bone graft substitute as well as identify patients possibly benefiting from Masquelet therapy using BaG and those who are more likely to fail, thereby improving the quality of non-union treatment., Trial Registration: German Clinical Trials Register (DRKS), ID: DRKS00013882 . Registered on 22 January 2018.

Background: The insertion of a chest tube should be as quick and accurate as possible to maximize the benefit and minimize possible complications for the patient. Therefore, comprehensive training and assessment before an emergency situation are essential for proficiency in chest tube insertion. Serious games have become more prevalent in surgical training because they enable students to study and train a procedure independently, and errors made have no effect on patients. However, up-to-date evidence regarding the effect of serious games on performance in procedures in emergency medicine remains scarce., Objective: The aim of this study was to investigate the serious gaming approach in teaching medical students an emergency procedure (chest tube insertion) using the app Touch Surgery and a modified objective structural assessment of technical skills (OSATS)., Methods: In a prospective, rater-blinded, randomized controlled trial, medical students were randomized into two groups: intervention group or control group. Touch Surgery has been established as an innovative and cost-free app for mobile devices. The fully automatic software enables users to train medical procedures and afterwards self-assess their training effort. The module chest tube insertion teaches each key step in the insertion of a chest tube and enables users the meticulous application of a chest tube. In contrast, the module "Thoracocentesis" discusses a basic thoracocentesis. All students attended a lecture regarding chest tube insertion (regular curriculum) and afterwards received a Touch Surgery training lesson: intervention group used the module chest tube insertion and the control group used Thoracocentesis as control training. Participants' performance in chest tube insertion on a porcine model was rated on-site via blinded face-to-face rating and via video recordings using a modified OSATS tool. Afterwards, every participant received an individual questionnaire for self-evaluation. Here, trainees gave information about their individual training level, as well as previous experiences, gender, and hobbies. Primary end point was operative performance during chest tube insertion by direct observance., Results: A total of 183 students enrolled, 116 students participated (63.4%), and 21 were excluded because of previous experiences in chest tube insertion. Students were randomized to the intervention group (49/95, 52%) and control group (46/95, 48%). The intervention group performed significantly better than the control group (Intervention group: 38.0 [I 50 =7.0] points; control group: 30.5 [I 50 =8.0] points; P<.001). The intervention group showed significantly improved economy of time and motion (P=.004), needed significantly less help (P<.001), and was more confident in handling of instruments (P<.001) than the control group., Conclusions: The results from this study show that serious games are a valid and effective tool in education of operative performance in chest tube insertion. We believe that serious games should be implemented in the surgical curriculum, as well as residency programs, in addition to traditional learning methods., Trial Registration: German Clinical Trials Register (DRKS) DRKS00009994; https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00009994 (Archived by Webcite at http://www.webcitation.org/6ytWF1CWg)., (©Patrick Haubruck, Felix Nickel, Julian Ober, Tilman Walker, Christian Bergdolt, Mirco Friedrich, Beat Peter Müller-Stich, Franziska Forchheim, Christian Fischer, Gerhard Schmidmaier, Michael C Tanner. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 21.05.2018.)

Background: Autologous bone grafting (ABG) remains the gold standard for augmentation of bone defects. The RIA system has become more prevalent, but evidence regarding risk management and complications remain scarce. This study presents the risk management and complications associated with RIA in the largest single-center case series to date., Methods: All records, operative notes, lab data and radiographs of patients receiving a RIA procedure at Heidelberg´s University Hospital between 01/01/2010 and 31/12/2016 were reviewed. Multivariate logistic regression models adjusting for clinically relevant covariates were used to examine the respective relevance regarding the presence and absence of prolonged postoperative pain (PPP)., Results: A total of 341 RIA procedures on 306 patients were performed at our level-1 trauma center. The femur was the main donor site (98.53%; N = 336) whereas only in 1.47% (N = 5) the tibia was utilized. A total of 11 patients showed a relevant loss of hemoglobin requiring blood transfusion. A total of 22 patients suffered from PPP directly associated with the RIA procedure resulting in prevalence of 6.45%. The 6 major complications in our study were of diverse origin and all intraoperative complications took place in the early phase of the RIA procedure in our center (2010-2013). Our data revealed influence of sex (p = 0.0459) and age (p = 0.0596) on the criterion PPP. The favored model including sex and age resulted in an AUC of 66.2% (CI: 55.5%-76.9%)., Conclusion: Perioperative blood loss remains a prevalent complication during RIA reaming. In addition, PPP occurs with a prevalence of 6.45%. This study showed a complication rate of 1.76%, emphasizing RIA´s overall safety and furthermore highlighting the need for vigilance in its application and prior extensive hands-on training of surgeons. Level of Evidence: II.

Background: Chest tube insertion is a standard intervention for management of various injuries of the thorax. Quick and accurate execution facilitates efficient therapy without further complications. Here, we propose a new training concept comprised of e-learning elements as well as continuous rating using an objective structured assessment of technical skills (OSATS) tool. The study protocol is presented for a randomized trial to evaluate e-learning with app-based serious gaming for chest drain insertion., Methods: The proposed randomized trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University in the context of regular curricular teaching for medical students (n = 90, 3rd to 6th year). The intervention group will use e-learning with the serious gaming app Touch Surgery (TM) for chest drain insertion, whereas the control group uses serious gaming for an unrelated procedure. Primary endpoint is operative performance of chest drain insertion in a porcine cadaveric model according to OSATS., Discussion: The randomized trial will help determine the value of e-learning with the serious gaming app Touch Surgery (TM) for chest drain insertion by using the OSATS score. The study will improve surgical training for trauma situations., Trial Registration: Trial Registration Number, DRKS00009994 . Registered on 27 May 2016.

Purpose: In total hip arthroplasty fixation of revision stems can be demanding due to femoral bone loss. Strut grafts are often used for bone augmentation and stabilization of the newly inserted prosthesis. The aim of this study was to assess the effect of strut grafts on primary stability under various stem fixation conditions., Methods: Two different revision stems (cylindrical and conical shape) were implanted into synthetic femora. Following a semicircular transfemoral osteotomy, three deficient femoral bearings were simulated (bony lid reattached with cable wires; weakened lid reattached with cable wires; strut grafts placed to the weakened lid with cable wires). Relative micro-movements were measured between prostheses and bones due to an axial moment applied to the stems., Results: Relative movements correlated to the stem shape. The cylindrical stem showed higher movements increasing significantly with a weakened bony lid and portrayed a slight decrease of movements with strut graft application. No unequivocal influence of the weakened lid could be detected for the conical implant. Strut graft application did not show an additional stabilizing effect., Conclusions: The primary stability of the cylindrical fixation concept decreases with impaired fixation conditions of the femur. A clear restabilizing effect with strut grafts could not be proven. A decrease of primary stability due to the impaired bone could not be observed for the conical stem shape. Additionally, strut grafts do not enhance fixation for this stem shape. We conclude that surgeons should not rely on a stabilizing effect of strut grafts in revision hip surgery.

Cementless surface replacement arthroplasties are increasingly being used to treat arthritic humeral heads. These implants are designed to provide narrow bone resection, making a later revision easier. However, no clear evidence exists as to whether their initial fixation is sufficient for bony ingrowth. The aim of our in vitro study was to characterize the relative micromotion of two resurfacing implants with essentially different bone-facing geometries. Both systems were implanted into 10 human humeral specimens and micromotion was measured under a cyclic torque application of up to ±1.75 Nm. The mean relative rotary motion resulted in a significant difference (p = 0.036), which was attributed to design differences of central stabilizers featuring both implants. A conversion of rotary motions into relative micromotions, using recently measured moments acting on these implants during daily activities of living, nullified this difference (p = 0.088). However, depending on the shoulder load case considered, a clear difference appeared (p = 0.031-0.045). In conclusion, both resurfacing implants are capable of achieving sufficient initial fixation on the humeral head and perform relative micromotions in a range considered safe for bony ingrowth. Patient-related parameters do not appear to influence the initial fixation of these implants., (Copyright © 2011 Orthopaedic Research Society.)

The glycoprotein IIb-IIIa inhibitor eptifibatide has been shown to be beneficial in the treatment of acute coronary syndromes and during percutaneous coronary intervention (PCI). Case reports of acute profound thrombocytopenia have been reported with eptifibatide, yet the true incidence of this reaction is unknown. We describe a 50-year-old woman with severe coronary artery disease who developed acute profound thrombocytopenia after readministration of eptifibatide. Eptifibatide was administered through hospital day 3, when it was discontinued in preparation for coronary angiography and PCI; the drug was restarted on day 5. On hospital day 6, she was noted to have a platelet count below 5 x 10(3)/mm,(3) indicating a profound decrease from a baseline of 456 x 10(3)/mm(3) on admission. Eptifibatide, heparin, vancomycin, and clopidogrel were potential causative agents. Anticoagulation and vancomycin were stopped, and her platelet count increased to 30 x 10(3)/mm(3) on day 7. Subsequent reexposure to heparin and vancomycin yielded no adverse effects. The patient's platelet count increased over the remainder of her hospitalization, and she was discharged home on day 19. Based on clinical presentation and negative heparin platelet factor 4 antibody test, eptifibatide was the most likely cause of thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated that eptifibatide was the probable cause of thrombocytopenia (score of 5); scores of 1 (possible) or 0 (doubtful) were derived with heparin, vancomycin, and clopidogrel. We conducted a literature search and compiled information from published case reports to describe the pattern of onset and recovery of eptifibatide-induced thrombocytopenia. In all patients receiving eptifibatide, routine platelet counts should be monitored at baseline and within 2-6 hours after starting the drug.

Background and Purpose: Caring has been identified as a rules-based approach to good patient care, as a core value in physical therapist professional behavior, as a part of experienced and expert practice, as a virtue, and as a moral orientation. Previous research showed that experienced and expert female physical therapists value compassion and caring in clinical practice. However, little is known about how novice physical therapists care for their patients. The purpose of this study was to explore the meaning of caring from the perspectives of novice physical therapists., Subjects: Seven novice physical therapists (with less than 1 year of clinical experience) working in either an outpatient or an inpatient facility were recruited., Methods: A qualitative method (phenomenology) was used, with data being obtained from retrospective interviews of the novice physical therapists regarding their experiences in the clinic., Results: Three common themes relating to the nature of caring emerged: learning to care (with the following subthemes: barriers to caring, the "difficult" patient, finding a balance, and time constraints), patients as subjects, and the culture of the clinic., Discussion and Conclusion: The novice physical therapists in this study expressed difficulty in dealing with difficult patients, with time management, and with balancing their professional and personal lives. However, despite the barriers to caring, many of these participants viewed caring not just as a rules-based approach but as a core value and, in some cases, a moral orientation that guided their first year of clinical practice. The findings suggest that caring requires certain skills and attitudes that accrue over time and that physical therapist education programs should integrate learning experiences (including clinical experiences) throughout the curriculum that foster caring behaviors in order to prepare students for the first-year transition in the clinic. In addition, experienced clinicians should appreciate how their clinic's culture and their behaviors can help model caring attitudes in novice physical therapists.

Purpose: To report short-term results of LASIK in 4 eyes with the vesicular form of posterior polymorphous dystrophy (PPMD)., Method: A review was performed of 2 patients with PPMD who underwent bilateral LASIK. Patients were asymptomatic at the time of presentation and had no prior ocular history. Preoperative measurements were made of uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), corneal pachymetry, and endothelial cell density (ECD). All 4 eyes underwent uneventful LASIK. Postoperative measurements of UCVA and BSCVA were performed at follow-up visits 1 day, 1 month, 3 months, and 1 year after surgery, along with pachymetry and ECD measurements at the 3-month and 1-year visits. Results were analyzed., Results: At 1 year, all eyes had an UCVA equal to or better than 20/25 and BSCVA equal to or better than 20/20. There was a small mean endothelial cell loss (2.3%) at 1 year. No adverse events were experienced., Conclusions: Short-term results indicate efficacy and safety of LASIK on eyes with posterior polymorphous dystrophy. Further study is needed to assess long-term outcomes in a larger study population.