[Evaluation of care for slipped capital femoral epiphysis (SCFE) in Germany]. / Analyse der Versorgungssituation bei Epiphyseolysis capitis femoris (ECF) in Deutschland.

INTRODUCTION: The treatment concept for slipped capital femoral epiphysis is still controversial. According to studies, there is currently no recommendation for a universal approach. Therefore, the aim of this study is to analyze the care reality of children with ECF in Germany. METHODS: The evaluation of the study is performed based on a questionnaire sent to physicians tending to ECF in 2021. Data is compared to the literature. RESULTS: 36 of 47 questionnaires sent out were included. Overall, no significant difference in ECF care was proven in terms of annual caseload or the size of hospital. CONCLUSION: A high variance in operative SCFE treatment is reported. According to current literature, the modified Dunn procedure is considered the best therapeutic option to date, especially for patients with severe or chronic ECF. However, compared with alternative care options, this is not feasible in every hospital due to its complicating and challenging nature. Central registration, minimum volume regulation, and expansion of continuing education measures can contribute to optimization.

[Radiographic analysis of limb malalignment in the frontal plane]. / Radiologische Analyse von Achsfehlstellungen des Knies in der Frontalebene.

Radiographic measurement of the lower limb alignment in the frontal plane is used to assess limb deformity, to plan corrective surgery and for follow-up. It is essential that age-related normal lower limb alignment and joint orientation angles are known before planning surgical treatment. EOS (EOS™ Imaging, Paris, France) can lead to supplemental information, especially in cases of severe multidimensional joint malalignment. It allows 3D reconstruction of a bone model of the limb to assess multi-dimensional deformity.

Correction to: Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study.

An amendment to this paper has been published and can be accessed via the original article.

Temporary hemiepiphysiodesis for correcting idiopathic and pathologic deformities of the knee: A retrospective analysis of 355 cases.

BACKGROUND: Hemiepiphysiodesis is a well-established treatment option in cases of pathologic deformities and leg discrepancies during evolution. The aim of this study was to evaluate the postoperative angular measurement, correction correlated with age at operation time, and postoperative complication rate. MATERIAL AND METHODS: A total of 355 patients were treated with 887 8-plates between April 2007 and January 2013. Their mean age was 12.18 years (range four to 16 years), and the mean time to axis correction was 17.32 months (range two to 62 months). We analysed the entire population and also performed subgroup analyses for idiopathic, pathologic, varus, valgus and leg length discrepancy. RESULTS: The mean durations (time from (hemi-) epiphysiodesis to implant removal) in the idiopathic and pathologic groups were 13.24 and 21.3 months, respectively. The time to implant removal was 18.39 months for idiopathic varus deformities and 11.07 months for idiopathic valgus deformities. For the pathologic deformity group it was 24.9 and 20 months in the varus and valgus subgroups, respectively. CONCLUSIONS: Hemiepiphysiodesis is a well-established treatment option to correct angular deformities. The rate of correction was slower and less successful in pathologic deformities and for leg length discrepancies. This suggests that earlier intervention is appropriate for these patients. A higher body mass index (BMI) was observed for valgus deformity, but no correlation was present between BMI and durability.

Outcomes of Noninvasively Treated Idiopathic Toe Walkers.

Idiopathic toe walking (ITW) causes a common problem in pediatric orthopaedics. In the literature, numerous treatment options have been reported, but consensus about the management of ITW is still missing. The aim of the current study was to evaluate conservative treatment with pyramidal insoles. A total of 193 patients underwent conservative treatment between January 2010 and June 2013. Mean age at the beginning of the treatment was 7.75 ± 0.23 years (range 2.0-17.0 years). For all patients, demographic data, comorbid diseases, passive range of motion (ROM), persistent toe walking, and performed operations were retrospectively evaluated. Following operative treatment was defined failure. Eight (4.15%) patients underwent Achilles tendon lengthening operation after mean therapy time of 2.72 years (range 0.1-7.0 years), 174 cases were treated successfully (90.16%). In 50 cases, toe walking suspended completely after mean therapy time of 2.83 years. In cases of failure, patients were older at diagnosis and at the beginning of the treatment. Mean passive ROM increased over the time. In cases of failure, ROM decreased from the first to the second examination. Conservative treatment of ITW using pyramidal insoles can be effective. Ankle dorsiflexion significantly improved in the patients who were successfully treated. Therapy should start early. A decrease of ROM under therapy should lead to critical revisal of individual therapy. Levels of Evidence: Therapeutic, level IV: Case series.

Bone cyst formation after ankle arthroplasty may be caused by stress shielding. A numerical simulation of the strain adaptive bone remodelling.

BACKGROUND: The history of total ankle arthroplasty (TAA) has different evolution steps to improve the outcome. The third generation implants show an overall 8-year survival rate up to 93%. The main reported reason for early failure of TAA is aseptic loosening, cyst formation is also frequently reported. The aim of the present study is to use the finite element (FE) method to analyze the adaptive bone remodeling processes, including cyst formation after TAA. METHODS: Bone characteristics applied to the model corresponded to information obtained from computed tomography. Finite element models for the tibia and the talus were developed and implant components were virtually implanted. RESULTS: The calculated total bone loss is 2% in the tibia and 17% in the talus. Cysts and areas of increased bone density were detectable dependent on prosthesis design in the tibia and talus. CONCLUSION: Our FE simulation provides a theoretical explanation for cyst formation and increasing bone density depending on implant design. However, cysts are not mono-causal, histo-chemical reactions should also be considered. Further clinical studies are necessary to evaluate the relevance of cyst formation and therapeutic strategies.

Vertex-Specific Proteins pUL17 and pUL25 Mechanically Reinforce Herpes Simplex Virus Capsids.

Using atomic force microscopy imaging and nanoindentation measurements, we investigated the effect of the minor capsid proteins pUL17 and pUL25 on the structural stability of icosahedral herpes simplex virus capsids. pUL17 and pUL25, which form the capsid vertex-specific component (CVSC), particularly contributed to capsid resilience along the 5-fold and 2-fold but not along the 3-fold icosahedral axes. Our detailed analyses, including quantitative mass spectrometry of the protein composition of the capsids, revealed that both pUL17 and pUL25 are required to stabilize the capsid shells at the vertices. This indicates that herpesviruses withstand the internal pressure that is generated during DNA genome packaging by locally reinforcing the mechanical sturdiness of the vertices, the most stressed part of the capsids.IMPORTANCE In this study, the structural, material properties of herpes simplex virus 1 were investigated. The capsid of herpes simplex virus is built up of a variety of proteins, and we scrutinized the influence of two of these proteins on the stability of the capsid. For this, we used a scanning force microscope that makes detailed, topographic images of the particles and that is able to perform mechanical deformation measurements. Using this approach, we revealed that both studied proteins play an essential role in viral stability. These new insights support us in forming a complete view on viral structure and furthermore could possibly help not only to develop specific antivirals but also to build protein shells with improved stability for drug delivery purposes.

[Influence of Comorbidities on Revision Rate within the First Year after Primary Total Hip Arthroplasty]. / Einfluss von Komorbiditäten auf die Revisionsrate im 1. Jahr postoperativ nach Primärimplantation einer Hüfttotalendoprothese.

Background Total hip arthroplasty (THA) is very frequently performed. Despite low complication rates, revisions play an important clinical and economical role. The aim of this study was to identify comorbid diseases of patients undergoing primary THA and their potential influence on the survival of hip replacements. Patients/Material and Methods A total of 867 patients were included in this retrospective study. All revisions were reviewed that took place at our hospital within one year of primary implantation of THA. Comorbid diseases were detected by administrative data, using the Elixhauser definition, which includes thirty diseases. The Cox regression model and Fisher's exact test were used to examine correlations between comorbidities and risk of revision. Results 41 Patients required re-operation within the first year of surgery. The presence of one or more of the analysed comorbidities was associated with a greater risk of revision. Deficiency anemia, obesity, drug abuse, alcohol abuse, fluid and electrolyte disorders and peripheral vascular disorders were associated with increased risk of revision (p < 0.05 for all comparisons). CONCLUSION: The total number of comorbidities and specific comorbid diseases was independently associated with an increased risk of re-operation within the first year of total hip arthroplasty. This information could be helpful in pre- and post-operative risk adjustment and patient selection.

Arthroplasty-center related retrospective analysis of risk factors for Periprosthetic Joint Infection after primary and after revision Total Hip Arthroplasty.

BACKGROUND: Periprosthetic Joint Infection (PJI) poses a great challenge to patients, surgeons and health care systems. Comorbid diseases and patient-related risk factors are poorly understood. OBJECTIVE: The purpose of this study was to evaluate patient-related risk factors for PJI after primary and after revision Total Hip Arthroplasty (THA). METHODS: In the present study, data was collected from 566 patients who underwent primary or revision THA between July 2011 and June 2012 in an established arthroplasty center (Endocert certified endoprosthesis center, EPZmax). The effects of demographic data and comorbid diseases on revision operations within 18 months following THA were analyzed using descriptive and explorative statistics. RESULTS: It was shown, that alcohol abuse, depression, preoperative ESBL (Extended Spectrum ß-Lactamase bacteria) infection, elevated preoperative serum-CRP (C-reactive protein), extended operation-time, extended length of hospital-stay, intraoperative complications, perioperative urinary tract infections and postoperative antibiotic therapy are significantly related to PJI in primary THA. CONCLUSIONS: Comorbid diseases seem to influence outcome after THA. They are important for predicting revision operations and implant survival. In severe high-risk cases, they can lead to perform the operation under precaution or to avoid performing the operation entirely. This should reduce PJI occurrences in future.

Subcellular trafficking and functional importance of herpes simplex virus type 1 glycoprotein M domains.

Herpes simplex virus type 1 (HSV-1) glycoprotein M (gM/UL10) is a 473 aa type III transmembrane protein that resides in various membrane compartments. HSV-1 gM contains several putative trafficking motifs, but their functional relevance remains to be elucidated. We show here that transiently expressed gM 19­343 was sufficient for transport to the trans-Golgi network (TGN), whilst gM 133­473, where the first two transmembrane domains were deleted, and gM 1­342, which lacked the final residue of the last transmembrane domain, were retained in the endoplasmic reticulum (ER), indicating that all transmembrane domains are required for proper folding and ER exit. A series of bacterial artificial chromosome mutants revealed that in addition to the authentic start codon, translation of gM can be initiated at methionine 19 and 133/135. Whilst a protein lacking the first 18 residues supported WT-like growth, gM 133/135­473 resulted in reduced plaque diameters resembling a UL10 deletion mutant. An HSV-1 mutant encoding gM 1­342 showed similar growth characteristics and accumulated non-enveloped cytoplasmic particles, whilst gM 1­343 resulted in a gain of function, indicating that all transmembrane domains of the protein are important for viral growth. A C-terminal extension further supported viral propagation; however, the C-terminal trafficking motifs (residues 423­473) were completely dispensable. We propose a functional core within gM 19­343 comprised of all transmembrane domains that is sufficient to target the protein to the TGN, a favoured site for envelopment, and to support viral functions.

Short-stem hip arthroplasty in osteonecrosis of the femoral head.

INTRODUCTION: Osteonecrosis of the femoral head (ONFH) is a locally destructive and complex disorder. Without treatment, infraction of the femoral head is likely. There is also a lack of consensus in the literature about the most appropriate arthroplasty method in patients with progressive ONFH. During the last decade, the number of short-stem prostheses has increased. Some short-stem designs have a metaphyseal anchorage. It is questionable whether ONFH represents a risk factor for failure after implantation of short stems. The aim of this study was to review existing literature regarding the outcome of short-stem arthroplasty in ONFH and to present the pros and cons of short-stem hip arthroplasty in osteonecrosis of the femoral head. MATERIALS AND METHODS: This review summarises existing studies on short-stem hip arthroplasty in osteonecrosis of the femoral head. RESULTS: Few studies have analysed the clinical and radiological outcome of short-stem THA in patients with ONFH. Only a handful of studies present clinical and radiological outcome after implantation of a short-stem arthroplasty in patients with the underlying diagnosis of osteonecrosis of the femoral head. CONCLUSION: The short- to medium-term results show predominantly good outcomes. However, due to differences in the design of short stems and their fixation, it is hard to draw a general conclusion. Short stems with primary diaphyseal fixation do not reveal a high increased risk of failed osseointegration or loosening. For designs with a primary metaphyseal anchorage, an MRI should be conducted to exclude that the ostenecrosis exceeds the femoral neck.

Preoperative diagnostic for periprosthetic joint infection prior to total knee revision arthroplasty.

Periprosthetic joint infection (PJI) after total knee arthroplasty remains a challenging problem. The aim of this study was to evaluate the accuracy of diagnostic knee aspiration and serum inflammatory markers in diagnostic of a PJI after total knee arthroplasty. Within 2011 and 2012, 46 patients received a one- or two-stage revision arthroplasty of the knee joint. These patients received a total number of 77 operations. A preoperative aspiration was performed in each case. We analyzed the microbiological and histological examinations of the samples from the aspiration and from the revision operation and additionally estimated serum inflammatory markers. The diagnostic aspiration had a specificity of 0.87, a sensitivity of 0.39, a positive predictive value of 0.67 and a negative predictive value of 0.68. For C-reactive protein the specificity was 0.61 and the sensitivity was 0.48, the serum white blood cell count had a specificity of 0.98 and a sensitivity of 0.23. Our data queries whether diagnostic joint aspiration or serum inflammatory markers are sufficient to verify or exclude a PJI.

Outcomes with cementless total hip resurfacing: 5 year follow-up.

BACKGROUND: Resurfacing Arthroplasty (RA) of the hip has undergone resurgence with initially mainly good clinical results in young patients. It was mainly performed in younger more active patients with severe symptomatic arthritis of the hip including pelvic deformity. Furthermore the proximal femoral anatomy was preserved for surgical procedures in the future. OBJECTIVE: The aim of the study was to perform a prospective review of the very first 85 hips that had implantation of one cementless resurfacing system and a mean follow up of 5 years. METHODS: 85 cementless Total Hip Resurfacing devices have been performed in 75 patients in our orthopaedic department. The mean age of the study group was 49.8 years. Harries Hip Score, clinical examination data and radiographic parameters including the neck shaft angle (NSA), stem shaft angle (SSA) and detection of radiolucencies were analyzed. RESULTS: Estimated implant survival at five years of follow-up was 88.2% at 5 years follow-up using revision for all causes as the end point. Mean HHS was 92.5 (range 80-100) five years after Resurfacing Arthroplasty. CONCLUSIONS: In conclusion we have to admit, that there was a high proportion of failed hip resurfacings but in the proportion that succeeded we saw good clinical results.

A precipitation-based assay to analyze interactions of viral particles with cytosolic host factors.

Since viruses are obligate intracellular parasites, viral particles, subviral structures, and viral proteins enlist the support of host proteins to foster intracellular transport, viral gene expression, replication, and evasion from antiviral host responses. We have devised a biochemical in vitro method to analyze specific interactions of cytosolic factors with capsids of herpes simplex virus and to characterize host proteins that specifically coprecipitate with different types of viral particles by immunoblotting, mass spectrometry, and immunoelectron microscopy. Our method bridges the gap between assays such as co-immunoprecipitation and yeast-two-hybrid approaches that determine direct binding between individual subunits of protein complexes and microscopy methods that analyze the dynamic interplay between intact viral particles and host factor complexes in intact cells. Our protocol can be extended to functional analyses of herpesvirus capsids and other viral structures with more complex host structures such as microtubule transport, genome uncoating at nuclear pores, or capsid envelopment at host membranes.

Biodegradable magnesium-based screw clinically equivalent to titanium screw in hallux valgus surgery: short term results of the first prospective, randomized, controlled clinical pilot study.

PURPOSE: Nondegradable steel-and titanium-based implants are commonly used in orthopedic surgery. Although they provide maximal stability, they are also associated with interference on imaging modalities, may induce stress shielding, and additional explantation procedures may be necessary. Alternatively, degradable polymer implants are mechanically weaker and induce foreign body reactions. Degradable magnesium-based stents are currently being investigated in clinical trials for use in cardiovascular medicine. The magnesium alloy MgYREZr demonstrates good biocompatibility and osteoconductive properties. The aim of this prospective, randomized, clinical pilot trial was to determine if magnesium-based MgYREZr screws are equivalent to standard titanium screws for fixation during chevron osteotomy in patients with a mild hallux valgus. METHODS: Patients (n=26) were randomly assigned to undergo osteosynthesis using either titanium or degradable magnesium-based implants of the same design. The 6 month follow-up period included clinical, laboratory, and radiographic assessments. RESULTS: No significant differences were found in terms of the American Orthopaedic Foot and Ankle Society (AOFAS) score for hallux, visual analog scale for pain assessment, or range of motion (ROM) of the first metatarsophalangeal joint (MTPJ). No foreign body reactions, osteolysis, or systemic inflammatory reactions were detected. The groups were not significantly different in terms of radiographic or laboratory results. CONCLUSION: The radiographic and clinical results of this prospective controlled study demonstrate that degradable magnesium-based screws are equivalent to titanium screws for the treatment of mild hallux valgus deformities.

Inhibition of the host translation shutoff response by herpes simplex virus 1 triggers nuclear envelope-derived autophagy.

Macroautophagy is a cellular pathway that degrades intracellular pathogens and contributes to antigen presentation. Herpes simplex virus 1 (HSV-1) infection triggers both macroautophagy and an additional form of autophagy that uses the nuclear envelope as a source of membrane. The present study constitutes the first in-depth analysis of nuclear envelope-derived autophagy (NEDA). We established LC3a as a marker that allowed us to distinguish between NEDA and macroautophagy in both immunofluorescence and flow cytometry. NEDA was observed in many different cell types, indicating that it is a general response to HSV-1 infection. This autophagic pathway is known to depend on the viral protein γ34.5, which can inhibit macroautophagy via binding to beclin-1. Using mutant viruses, we were able to show that binding of beclin-1 by γ34.5 had no effect on NEDA, demonstrating that NEDA is regulated differently than macroautophagy. Instead, NEDA was triggered in response to γ34.5 binding to protein phosphatase 1α, an interaction used by the virus to prevent host cells from shutting off protein translation. NEDA was not triggered when late viral protein production was inhibited with acyclovir or hippuristanol, indicating that the accumulation of these proteins might stress infected cells. Interestingly, expression of the late viral protein gH was sufficient to rescue NEDA in the context of infection with a virus that otherwise does not support strong late viral protein expression. We argue that NEDA is a cellular stress response triggered late during HSV-1 infection and might compensate for the viral alteration of the macroautophagic response.

Proteomics analysis of herpes simplex virus type 1-infected cells reveals dynamic changes of viral protein expression, ubiquitylation, and phosphorylation.

Herpesviruses are among the most complex and widespread human viruses and cause a number of diseases ranging from cold sores to genital infections and encephalitis. While the composition of viral particles has been studied, less is known about the expression of the whole viral proteome in infected cells. Here, we analyzed the proteome of the prototypical Herpes Simplex Virus type 1 (HSV1) in infected cells by mass spectrometry. Using a high sensitivity LTQ-Orbitrap, we achieved a very high level of protein coverage and identified a total of 67 structural and nonstructural viral proteins. We also identified 90 novel phosphorylation sites and 10 novel ubiquitylation sites on different viral proteins. Ubiquitylation was observed on nine HSV1 proteins. We identified phosphorylation sites on about half of the detected viral proteins; many of the highly phosphorylated ones are known to regulate gene expression. Treatment with inhibitors of DNA replication induced changes of both viral protein abundance and modifications, highlighting the interdependence of viral proteins during the life cycle. Given the importance of expression dynamics, ubiquitylation, and phosphorylation for protein function, these findings will serve as important tools for future studies on herpesvirus biology.

Herpesviruses exploit several host compartments for envelopment.

Enveloped viruses acquire their host-derived membrane at a variety of intracellular locations. Herpesviruses are complex entities that undergo several budding and fusion events during an infection. All members of this large family are believed to share a similar life cycle. However, they seemingly differ in terms of acquisition of their mature envelope. Herpes simplex virus is often believed to bud into an existing intracellular compartment, while the related cytomegalovirus may acquire its final envelope from a novel virus-induced assembly compartment. This review focuses on recent advances in the characterization of cellular compartment(s) potentially contributing to herpes virion final envelopment. It also examines the common points between seemingly distinct envelopment pathways and highlights the dynamic nature of intracellular compartments in the context of herpesvirus infections.