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Derralynn Hughes,1 Aleš Linhart,2 Andrey Gurevich,3 Vasiliki Kalampoki,3 Dalia Jazukeviciene,3 Sandro Feriozzi4 On behalf of the FOS Study Group1University College London and Royal Free London NHS Foundation Trust, London, UK; 2Charles University, First Faculty of Medicine, Prague, Czech Republic; 3Takeda Pharmaceuticals International AG, Zurich, Switzerland; 4Nephrology and Dialysis Unit, Belcolle Hospital, Department of Nephrology and Dialysis, Viterbo, ItalyCorrespondence: Derralynn HughesUniversity College London and Royal Free London NHS Foundation Trust, Pond Street, London, NW3 2QG, UKEmail derralynnhughes@nhs.netBackground: The timing of enzyme replacement therapy initiation in patients with Fabry disease is hypothesized to be critical. In this study, we used Fabry Outcome Survey data to assess the impact of prompt versus delayed initiation of treatment with agalsidase alfa on cardiovascular and renal events in patients with Fabry disease.Methods: Available genetic data at baseline were used to define patients with mutations associated with classical versus late-onset Fabry disease. Time to cardiovascular or renal events, from treatment initiation until 120 months, was compared for patients in prompt versus delayed groups. “Prompt” was defined as treatment initiation < 24 months from symptom onset (analysis A) or diagnosis (analysis B), and “delayed” was defined as ≥ 24 months from symptom onset (analysis A) or diagnosis (analysis B). Kaplan–Meier curves and Log rank tests compared event-free probabilities and time to first event. Multivariate Cox regression estimated hazard ratios (HRs).Results: Analysis by time from symptom onset included 1374 patients (172 prompt, 1202 delayed). In a multivariate Cox regression analysis, prompt versus delayed treatment initiation significantly reduced the probability of cardiovascular (HR=0.62; P< 0.001) and renal (HR=0.57; P=0.001) events. History of cardiovascular or renal events was associated with increased risk of respective events. Analysis by time from diagnosis included 2051 patients (1006 prompt, 1045 delayed). In a multivariate Cox regression analysis, prompt treatment initiation significantly reduced the probability of cardiovascular events (HR=0.83; P=0.003) after adjusting for history of cardiovascular events, sex, and age at treatment initiation. Univariate analysis showed that the probability of renal events was significantly lower in the prompt group (P=0.018); this finding was attenuated in the multivariate Cox regression analysis.Conclusion: This analysis suggests that prompt treatment initiation with agalsidase alfa provided better renal and cardiovascular outcomes than delayed treatment in patients with Fabry disease.Keywords: cardiomyopathies, nephrology, mutation, therapeutics, early diagnosis

Rossella Parini,1,2 Guillem Pintos-Morell,3 Julia B Hennermann,4 Ting-Rong Hsu,5 Nesrin Karabul,6 Vasiliki Kalampoki,7 Andrey Gurevich,7 Uma Ramaswami8 On behalf of the FOS Study Group1Rare Metabolic Diseases Unit, MBBM Foundation, San Gerardo Hospital, Reference Centre for Hereditary Metabolic Disorders (MetabERN), Monza, Italy; 2TIGET Institute, IRCCS San Raffaele Hospital, Milan, Italy; 3Division of Rare Diseases, Reference Centre for Hereditary Metabolic Disorders (MetabERN), University Hospital Vall d’Hebron, Autonomous University of Barcelona, Barcelona, Spain; 4Villa Metabolica, Department of Pediatric and Adolescent Medicine, University Medical Center, Mainz, Germany; 5Department of Pediatrics, Taipei Veterans General Hospital and Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Department of Neuropaediatric and Inborn Metabolic Disorders (Metabolicum Ruhr), University Children’s Hospital and Centre for Rare Diseases, Ruhr University Bochum, Bochum, Germany; 7Shire, a Takeda company, Zurich, Switzerland; 8Royal Free London NHS Foundation Trust, London, UKCorrespondence: Rossella PariniRare Metabolic Diseases Unit, MBBM Foundation, San Gerardo Hospital, Via Pergolesi 33, Monza 20900, ItalyEmail Rossella.parini@unimib.itPurpose: To determine the impact of initiating enzyme replacement therapy (ERT) with agalsidase alfa early in the course of Fabry disease, we evaluated renal and cardiac outcomes for ≤ 10 years after ERT initiation in males from the Fabry Outcome Survey (FOS).Patients and Methods: Male patients from FOS were stratified into three cohorts by age at ERT initiation: ≤ 18 years (cohort 1), > 18 and ≤ 30 years (cohort 2), and > 30 years (cohort 3). Analysis included age at symptom onset, diagnosis, and ERT initiation; ERT duration; FOS-Mainz Severity Score Index (FOS-MSSI); estimated glomerular filtration rate (eGFR); proteinuria level; and left ventricular mass indexed to height (LVMI). Mixed-effect models estimated renal and cardiac outcomes during follow-up between and within cohorts.Findings: The analysis included 560 male patients: 151 (27.0%) in cohort 1, 155 (27.7%) in cohort 2, and 254 (45.4%) in cohort 3. Mean±SD duration of ERT for cohorts 1, 2, and 3 was 6.3± 4.3, 8.6± 4.9, and 7.9± 4.9 years, respectively. Mean±SD baseline FOS-MSSI scores increased with age from 9.8± 7.2 in cohort 1 to 24.7± 11.4 in cohort 3. Cohort 3 showed the lowest baseline mean±SD value for eGFR (87.1± 29.0 mL/min/1.73m2) and highest baseline mean±SD values for proteinuria (801.9± 952.6 mg/day) and LVMI (56.7± 16.0 g/m2.7) among the three cohorts. Evaluation of mean annual rates of change in eGFR, proteinuria, and LVMI revealed no significant differences in any parameter for cohort 1. For cohort 2, proteinuria and LVMI remained stable, whereas eGFR significantly deteriorated annually (– 1.12 mL/min/1.73m2; P< 0.001). Cohort 3 demonstrated significant annual deteriorations in eGFR (– 2.60 mL/min/1.73m2; P< 0.001), proteinuria (+34.10 mg/day; P< 0.001), and LVMI (+0.59 g/m2.7; P=0.001).Implications: Renal and/or cardiac disease progression appears attenuated in patients starting ERT in childhood or early adulthood versus patients starting ERT in later adulthood. These findings support early ERT initiation in Fabry disease. ClinicalTrials.gov identifier: NCT03289065.Keywords: agalsidase alfa, Fabry disease, enzyme replacement therapy, Fabry Outcome Survey, estimated glomerular filtration rate, left ventricular hypertrophy

Purpose: The initiation of enzyme-replacement therapy prior to the occurrence of substantial and irreversible organ damage in patients with Fabry disease is of critical importance. The Fabry Outcome Survey is an international disease registry of patients with a confirmed diagnosis of Fabry disease. In this study, data from the Fabry Outcome Survey were used for the assessment of the risks for cardiovascular and renal events in patients who received agalsidase alfa treatment., Methods: Eligible patients were males and females aged ≥18 years with Fabry disease treated with agalsidase alfa. Cardiovascular events included myocardial infarction, left ventricular hypertrophy (LVH), heart failure, arrhythmia, conduction abnormality, and cardiac surgery. Renal events included dialysis, transplantation, and renal failure. Kaplan-Meier curves and log-rank tests were used for comparing event-free probabilities and time to first cardiovascular or renal event, from agalsidase alfa initiation to a maximum of 120 months, in patients with LVH versus normal left ventricular mass index (LVMI; ≤50 g/m 2.7 in males and ≤48 g/m 2.7 in females) at treatment initiation (baseline), and in patients with a low estimated glomerular filtration rate (eGFR; <90 mL/min/1.73 m 2 ) versus normal eGFR at baseline. Multivariate Cox regression analysis was used for examining the association between key study variables and the risks for cardiovascular and renal events., Findings: Among the 560 patients (269 males; 291 females) with available LVMI data, 306 (55%) had LVH and 254 (45%) had normal LVMI at baseline. The risk for a cardiovascular event was higher in the subgroup with LVH versus normal LVMI at baseline (hazard ratio [HR] = 1.57; 95% CI, 1.21-2.05; P < 0.001), but the risk for a renal event was similar between the 2 subgroups (HR = 1.90; 95% CI, 0.94-3.85; P = 0.074). Among the 1093 patients (551 males; 542 females) with available eGFR data, 433 (40%) had a low eGFR and 660 (60%) had a normal eGFR at baseline. The subgroup with a low eGFR at baseline had a significantly higher risk for a cardiovascular event (HR = 1.33; 95% CI, 1.04-1.70; P = 0.021) or a renal event (HR = 5.88; 95% CI, 2.73-12.68; P < 0.001) compared with patients with a normal eGFR at baseline., Implications: In the present study, the presence of LVH and/or reduced renal function at agalsidase alfa initiation was associated with a significantly higher risk for a cardiovascular or renal event, indicating that cardiovascular and renal pathologies in Fabry disease may be inter-related. Early initiation of agalsidase alfa treatment prior to the onset of severe organ damage may improve outcomes. ClinicalTrials.gov identifier: NCT03289065., Competing Interests: Disclosures Shire International GmbH, a Takeda company, funded this research, its publication, and the writing and editing of the manuscript, and was involved in the study design; the collection, analysis, and interpretation of the data; the writing of the report; and the decision to submit the article for publication. The FOS is sponsored by Shire Human Genetic Therapies Inc. a Takeda company. Dr. Feriozzi reports personal and travel fees from Takeda, personal and travel fees from Sanofi, personal and travel fees from Amicus, outside the submitted work; Dr. Linhart reports grants and personal fees from Amicus Therapeutics, grants and personal fees from Sanofi Genzyme, grants and personal fees from Takeda, outside the submitted work; Dr. Ramaswami reports grants and personal fees from Amicus, personal fees from Chiesi, personal fees from Sanofi Genzyme, grants from Takeda, outside the submitted work, and she is also a member of the Steering Committee of the Fabry Outcome Survey; Ms. Kalampoki was an employee of Takeda during the conduct of this study; Dr. Gurevich was an employee of Takeda during the conduct of this study; Dr. Hughes reports personal fees from Takeda, personal fees from Sanofi, personal fees from Amicus, personal fees from Idorsia, personal fees from Protalix, personal fees from Freeline, outside the submitted work, and she is also a member of the Steering Committee of the Fabry Outcome Survey., (Copyright © 2020 Takeda Pharmaceutical Company. Published by Elsevier Inc. All rights reserved.)

Purpose: The primary objective was to identify the predictors of in-hospital mortality after pelvic ring injuries. Secondary objectives were to analyze the differences between adults and children and to analyze the causes and timing of death., Methods: A retrospective cohort study from the pelvic registry of Assiut University Trauma Unit (AUTU), a level 1 trauma centre in Upper Egypt, was carried out. A total of 1188 consecutive patients with pelvic ring fractures treated from January 2010 to December 2013 were eligible for analysis. Potential predictors were identified using standard statistical tests: univariable and multivariable regression analysis., Results: Nine hundred fifty-one were adults (above 16 years) and 237 were children. According to Tile's classification, fractures type A, B, and C were 31.8%, 25.1%, and 43.1%, respectively. About a third of patients had fractures with soft tissue injury. Abdominopelvic collection as diagnosed by Focused Assessment with Sonography for Trauma (FAST) was positive in 11%. Associated injuries were present in 67.3% with abdominal-urogenital injuries being the most prevalent (66.3%). Median hospital stay was five days. Fifty-two patients (4.4%) were admitted to the ICU. One hundred three patients died (8.7%) within two peaks: first 24 hours and between 48 hours and one week. Multivariable logistic regression analysis identified increasing age, fractures with soft tissue injury, associated head injury, positive FAST examination, and admission to an ICU as significant predictors of in-hospital mortality., Conclusions: The first 24 hours were confirmed to be critical for survival in pelvic fracture patients. Advancing age, associated soft tissue injury, associated head injury, admission to ICU, and positive FAST examination can serve as reliable predictors for an elevated mortality risk in such patients.

Objective: To gain information about the advantages/disadvantages of an implementation of patient-reported outcome measures (PROM) into the clinical routine of trauma/orthopaedic surgeons, and to identify the technical constraints confronting a successful implementation of PROMs., Design: Online survey., Participants: Surgeons who are members of the AO Foundation., Measures: Participants answered questions regarding demographics, their familiarity with specific and generic PROMs and the use of PROMs in clinical routine. Furthermore, reasons for/against using PROMs, why not used more often, prerequisites to implement PROMs into clinical routine and whether PROMs would be implemented if adequate tools/technologies were available, were solicited. Χ 2 tests and multivariable logistic regressions were conducted to evaluate the effect of the AO Region, surgeon specialisation, current position, clinical experience, and workplace on the familiarity with disease-specific PROMs, the familiarity with generic PROMs and the current use of PROMs. Exploratory factor analysis was used to identify issues underlying the extent of PROM usage., Results: 1212 surgeons completed the survey (response rate: 6.8%; margin of error: ±2.72%): 54.2% were trauma/orthopaedic surgeons, 16.6% were spine surgeons, 27.9% were craniomaxillofacial surgeons and 16 had no defined specialty. Working in a certain AO Region, surgical specialisation and current workplace were associated with a higher familiarity of disease-specific PROMs and the use of PROMs in daily clinical routine (p≤0.05). Exploratory factor analysis identified four categories important for the use of PROMs and two categories preventing the use of PROMs. In case of the availability of an adequate tool, 66.2% of surgeons would implement PROMs in clinical routine., Conclusions: Our survey results provide an understanding of the use of PROMs in clinical routine. There is consensus on the usefulness of PROMs. User-friendly and efficient tools/technologies would be a prerequisite for the daily use of PROMs. Additionally, educational efforts and/or policies might help., Competing Interests: Competing interests: We received financial support from AOCID and AOTrauma for the submitted work; AJ, CK, AB and VK are employees of AOCID; no other relationships or activities that could appear to have influenced the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

During the last few decades, the recombinant protein expression finds more and more applications. The cloning of protein-coding genes into expression vectors is required to be directional for proper expression, and versatile in order to facilitate gene insertion in multiple different vectors for expression tests. In this study, the TA-GC cloning method is proposed, as a new, simple and efficient method for the directional cloning of protein-coding genes in expression vectors. The presented method features several advantages over existing methods, which tend to be relatively more labour intensive, inflexible or expensive. The proposed method relies on the complementarity between single A- and G-overhangs of the protein-coding gene, obtained after a short incubation with T4 DNA polymerase, and T and C overhangs of the novel vector pET-BccI, created after digestion with the restriction endonuclease BccI. The novel protein-expression vector pET-BccI also facilitates the screening of transformed colonies for recombinant transformants. Evaluation experiments of the proposed TA-GC cloning method showed that 81% of the transformed colonies contained recombinant pET-BccI plasmids, and 98% of the recombinant colonies expressed the desired protein. This demonstrates that TA-GC cloning could be a valuable method for cloning protein-coding genes in expression vectors.

Background: The recurrence rate of cervical chordomas is high, and hence it is important to discern the prognostic factors for local relapse and overall survival (OS)., Methods: A retrospective review of 52 patients with cervical chordoma operated in our institution from January 1999 to March 2015 was performed. The association of clinicopathologic characteristics with local relapse-free survival (LRFS) and OS was analyzed. Univariate analysis was performed to determine whether tumor characteristics and types of therapy affected prognosis, and a multivariate Cox proportional hazard model was developed to further investigate local recurrence and mortality., Results: Mean follow-up time was 50 months. The cumulative 5- and 10-year LRFS was 35 and 0%, respectively, while the cumulative 5- and 10-year OS was 69 and 53%, respectively. The univariate analysis identified contiguous segments involved, intralesional surgical margin at primary surgery, primary surgery in local hospital, incisional biopsy, and without adjuvant radiotherapy as negative prognostic factors for LRFS, whereas for OS, only tumor location in the upper cervical spine was statistically significant. In the multivariate analysis, contiguous vertebral segments involved, intralesional surgical margins, and incisional biopsy were identified as negative prognostic factors for LRFS, whereas for OS, again only tumor location in the upper cervical spine was statistically significant., Conclusions: Contiguous vertebral segments involved, intralesional surgical margin, without adjuvant radiotherapy, and incisional biopsy significantly increase local recurrence, while tumor location in the upper cervical spine significantly increases tumor-related mortality. Thus, computed tomography-guided fine-needle aspiration biopsy and total spondylectomy with marginal excision may improve survival of patients with cervical chordoma.

Introduction: Treatment of fractures in the elderly population is a clinical challenge due partly to the presence of comorbidities. In a Geriatric Fracture Centre (GFC), patients are co-managed by a geriatrician in an attempt to improve clinical outcomes and reduce morbidity and mortality. Until now the beneficial effect of orthogeriatric co-management has not been definitively proven. The primary objective of this study is to determine the effect of GFC on predefined major adverse events related to a hip fracture compared to usual care centres (UCC). The secondary objectives include assessments in quality of life, patient-reported outcomes and cost-effectiveness., Methods and Analysis: Two hundred and sixty-six elderly patients diagnosedwith hip fracture and planned to be treated with osteosynthesis or endoprosthesis in either a GFC or UCC study site will be recruited, 133 per type of centre. All procedures and management will be done according to the site's standard of care. Study-related visits will be performed at the following time points: preoperative, intraoperative, discharge from the orthopaedic/trauma department, discharge to definite residential status, 12 weeks and 12 months postsurgery. Data collected include demographics, residential status, adverse events, patient-reported outcomes, fall history, costs and resources related to treatment. The risk of major adverse events at 12 months will be calculated for each centre type; patient-reported outcomes will be analysed by mixed effects regression models to estimate differences in mean scores between baseline and follow-ups whereas cost-effectiveness will be assessed using the incremental cost-effectiveness ratio., Ethics and Dissemination: Ethics approval for this study was granted from the local Ethics Committees or Institutional Review Board from each of the participating sites prior to patient enrolment. The results of this study will be published in peer-reviewed journals and presented at different conferences., Trial Registration Number: ClinicalTrials.gov: NCT02297581; pre-results., Competing Interests: Competing interests: AH-C, AJ, DH and VK are AOCID employees and receive salary from the AO Foundation., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Study Design: Systematic literature review with meta-analysis., Objective: Thoracolumbar (TL) fractures can be treated conservatively or surgically. Especially, the treatment strategy for incomplete and complete TL burst fractures (A3 and A4, AOSpine classification) in neurologically intact patients remains controversial. The aim of this work was to collate the clinical evidence on the respective treatment modalities., Methods: Searches were performed in PubMed and the Web of Science. Clinical and radiological outcome data were collected. For studies comparing operative with nonoperative treatment, the standardized mean differences (SMD) for disability and pain were calculated and methodological quality and risk of bias were assessed., Results: From 1929 initial matches, 12 were eligible. Four of these compared surgical with conservative treatment. A comparative analysis of radiological results was not possible due to a lack of uniform reporting. Differences in clinical outcomes at follow-up were small, both between studies and between treatment groups. The SMD was 0.00 (95% CI -0.072, 0.72) for disability and -0.05 (95% CI -0.91, 0.81) for pain. Methodological quality was high in most studies and no evidence of publication bias was revealed., Conclusions: We did not find differences in disability or pain outcomes between operative and nonoperative treatment of A3 and A4 TL fractures in neurologically intact patients. Notwithstanding, the available scores have been developed and validated for degenerative diseases; thus, their suitability in trauma may be questionable. Specific and uniform outcome parameters need to be defined and enforced for the evaluation of TL trauma., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Three authors (Elke Rometsch, Brigitte Sandra Gallo-Kopf, and Vasiliki Kalampoki) are employees of AO Foundation in the Department of Clinical Investigation and Documentation (AOCID). Concerning the work under consideration, Frank Kandziora has received travel support and honorary for board meetings by AO Spine. Financial activities outside the submitted work within the preceding 36 months are reported by Maarten Spruit for his activities as Chairman of AO TK Spine, by Frank Kandziora for his activities as a consultant for DePuy-Synthes, Siemens, and Silony, by Roger Härtl for his activities as a consultant for Brainlab, Lanx, Depuy-Synthes and AOSpine, and by Robert Alton McGuire for review of medical records for Rehab, Inc.

Background: Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined., Methods: In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP., Results: The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P = .003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P = .002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P = .012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P = .038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876)., Conclusions: The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Only a few studies have been conducted with the objective of creating norms of the Alberta Infant Motor Scale (AIMS) for the assessment of gross motor development of preterm infants. The AIMS performance of preterm infants has been compared with that of the Canadian norms of full-term infants, but not with that of full-term infants of the same nationality. Moreover, the possible impact of prematurity-related morbidity factors on AIMS performance is unknown., Objectives: The aims of this study were: (1) to evaluate AIMS trajectory in a large population of Greek preterm infants and create norms, (2) to compare it with the AIMS trajectory of Greek full-term infants, and (3) to examine the possible influence of neonatal morbidity on AIMS scores in the preterm sample., Design: This was a cross-sectional study., Methods: Mean AIMS scores were compared, per month (1-19), between 403 preterm infants (≤32 weeks of age, corrected for prematurity) and 1,038 full-term infants. In preterm infants, the association of AIMS scores with respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) of grade ≤III, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and sepsis was assessed by hierarchical regression analysis., Results: Alberta Infant Motor Scale scores were significantly lower in preterm infants than in full-term infants. Mean AIMS scores in preterm infants were significantly associated with RDS (b=-1.93; 95% CI=-2.70, -1.16), IVH (b=-0.97; 95% CI=-1.69, -0.25), and ROP (b=-1.12; 95% CI=-1.99, -0.24) but not with BPD or sepsis in hierarchical regression analysis., Conclusions: Alberta Infant Motor Scale norms were created for Greek preterm infants. This study confirms that AIMS trajectories of preterm infants are below those of full-term infants of the same nationality. The influence of morbidity factors, including RDS, IVH, and ROP, should be taken into account when administering the AIMS in preterm infants., (© 2016 American Physical Therapy Association.)

Background: Resuming work after surgical treatment of an unstable pelvic ring injury is often impeded because of residual disability. The aim of this study was to test which factors influence return to work, ability to return to the same job function as before the injury, leaves of absence, and incapacitation after sustaining a pelvic fracture., Materials and Methods: We performed a retrospective study on patients with surgically treated pelvic fractures. Medical records were reviewed to document patients' demographic data, the extent of follow-up care, diagnosis of the injury (according to the Tile system of classification), type of surgical treatment, injury severity, and the time from trauma to definitive surgery. We also recorded the classification of patients' physical status according to the American Society of Anesthesiologists (ASA) and details about admission to the intensive care unit (ICU). Patients were interviewed to note the number of days before returning to work and their ability to maintain their previously held jobs., Results: Fifty patients were included in the study, and their mean age was 46.3 ± 12.6 years. The median time to return to work was 195 days. Twelve patients (24 %) lost their jobs and 17 (34 %) resumed their previous job with a change of tasks. ICU admission and time from trauma to definitive surgery were negatively correlated with return to the previously held job. Returning to the same job tasks was not associated with any of the factors investigated. Polytrauma, ICU admission, and time from trauma to definitive surgery were associated with longer leaves of absence., Conclusions: Work reintegration after pelvic ring injuries is a major issue for patients and health care systems: 58 % of patients were not able to return to or lost their job. Factors correlated with leaves of absence were injury severity, delayed definitive fixation, and ICU admission., Level of Evidence: IV (case series).

Introduction: A systematic literature review on periprosthetic/interprosthetic fracture fixation after hip arthroplasties was performed to summarize available clinical data. Operation techniques and implants used were evaluated as possible risk factors for outcomes., Materials and Methods: MEDLINE and Cochrane databases were searched. Articles describing patients with postoperative periprosthetic femur fractures sustained around a hip arthroplasty and with interprosthetic fractures treated with plates, nails, screws and/or cerclage were included. Considered articles were from 2000 or newer. Eligible abstracts were screened by two independent persons and discrepancies were resolved by consensus. Absolute numbers of complications and/or reoperation events along with their corresponding rates were calculated according to operation technique and type of implant. Relative risks of having a complication and/or a reoperation according to the operation technique and the type of implant used were estimated., Results: Available data from 49 prospective and retrospective studies were analyzed. Of 1574 fractures, 81.7 % were treated with plating. For 83.0 % of all fractures, an open approach was applied. The overall complication rate was 14.3 %. Fixation failure and nonunion were most often reported (fixation failure: 4.4 %; nonunion: 3.9 %). Nonunion and refracture occurred more often after open approaches than after minimal invasive osteosynthesis (nonunion: 4.5 vs. 0.0 %, p = 0.001; refracture: 3.8 vs. 0.6 %. p = 0.024). The relative risk for nonunion was 11.9 (95 % CI 4.5-31.5) times higher (p < 0.0001) for non-locking plates (13.0 %) than for locking plates (1.1 %)., Conclusions: The clinical evidence of published studies dealing with periprosthetic/interprosthetic fractures after hip arthroplasty is generally low. This literature search suggested higher rates of nonunion and refracture after an open approach and a higher risk of nonunion for non-locking plates compared to locking plates. Based on the available clinical evidence, no treatment recommendations can be given.

Introduction: Pelvic fractures requiring surgical fixation are rare injuries but present a great societal impact in terms of disability, as well as economic resources. In the literature, there is no description of these costs. Main aim of this study is to describe the direct and indirect costs of these fractures. Secondary aims were to test if the type of fracture (pelvic ring injury or acetabular fracture) influences these costs (hospitalization, consultation, medication, physiotherapy sessions, job absenteeism)., Materials and Methods: We performed a retrospective study on patients with surgically treated acetabular fractures or pelvic ring injuries. Medical records were reviewed in terms of demographic data, follow-up, diagnosis (according to Letournel and Tile classifications for acetabular and pelvic fractures, respectively) and type of surgical treatment. Patients were interviewed about hospitalization length, consultations after discharge, medications, physiotherapy sessions and absenteeism., Results: The study comprised 203 patients, with a mean age of 49.1 ± 15.6 years, who had undergone surgery for an acetabular fracture or pelvic ring injury. The median treatment costs were 29.425 Euros per patient. Sixty percent of the total costs were attributed to health-related work absence. Median costs (in Euros) were 2.767 for hospitalization from trauma to definitive surgery, 4.530 for surgery, 3.018 for hospitalization in the surgical unit, 1.693 for hospitalization in the rehabilitation unit, 1.920 for physiotherapy after discharge and 402 for consultations after discharge. Total costs for treating pelvic ring injuries were higher than for acetabular fractures, mainly due to the significant higher costs of pelvic injuries regarding hospitalization from trauma to definitive surgery (p < 0.001) and hospitalization in the surgical unit (p = 0.008)., Conclusions: Pelvic fractures are associated with both high direct costs and substantial productivity loss.

Objective: The aims of this study were to investigate gross motor development in Greek infants and establish AIMS percentile curves and to examine possible association of AIMS scores with socioeconomic parameters., Methods: Mean AIMS scores of 1068 healthy Greek full-term infants were compared at monthly age level with the respective mean scores of the Canadian normative sample. In a subgroup of 345 study participants, parents provided, via interview, information about family socioeconomic status. Multiple linear regression analysis was performed to evaluate the relationship of infant motor development with socioeconomic parameters., Results: Mean AIMS scores did not differ significantly between Greek and Canadian infants in any of the 19 monthly levels of age. In multiple linear regression analysis, the educational level of the mother and also whether the infant was being raised by grandparents/babysitter were significantly associated with gross motor development (p=0.02 and p<0.001, respectively), whereas there was no significant correlation of mean AIMS scores with gender, birth order, maternal age, paternal educational level and family monthly income., Conclusions: Gross motor development of healthy Greek full-term infants, assessed by AIMS during the first 19months of age, follows a similar course to that of the original Canadian sample. Specific socioeconomic factors are associated with the infants' motor development., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The contact of the gastric refluxate with the lower esophagus results in an inflammatory-mediated tissue damage. The role of inflammation both in the development and in the advance of Barrett's esophagus (BE) has not been elucidated. The aim of this study was to assess the inflammatory infiltration in metaplastic Barrett's epithelium and to explore the association of microscopic inflammation to healed esophagitis and Barrett's length., Material and Methods: Inflammatory infiltration was qualitatively evaluated in well-characterized Barrett's specimens. Esophagitis was healed prior to histological sampling. Univariate comparative analysis was performed based on BE length., Results: Ninety-eight patients (78 male, mean age 58.3 ± 13.3 yrs) were retrospectively studied. Thirty-three cases with long segment BE (LSBE) (33.7%) were spotted. Inflammatory infiltration was mild, moderate, and severe in 35 (35.7%), 54 (55.1%), and 9 (9.1%) specimens, respectively. The samples with moderate/severe inflammatory infiltration were obtained from patients who had more frequently been diagnosed with esophagitis (p = 0.025). Hiatal hernia (p = 0.001), esophagitis (p = 0.019), and previous use of anti-secretory drugs (p = 0.005) were more common in LSBE., Conclusions: Inflammatory infiltration of Barrett's epithelium was largely moderate despite preceding healing of erosions with PPIs. Previous diagnosis of esophagitis correlated to the degree of inflammation. No association of inflammation to Barrett's length was established.

Background: Barrett's esophagus (BE) is a major complication of gastroesophageal reflux disease due to its neoplastic potential. The length of the metaplastic epithelium has been associated with cancer risk. Angiogenesis, inflammation, and increased cell proliferation are early events in the malignant sequence. Vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and Ki-67 are indirect markers of these complex mechanisms., Aims: To examine the expression of VEGF, COX-2 and Ki-67 in BE and investigate whether there is an association to Barrett's length., Methods: Immunohistochemistry for VEGF, COX-2, and Ki-67 was performed in well-characterized Barrett's samples, evaluated using a qualitative scale and compared between long (LSBE) and short (SSBE) segments., Results: The study population consisted of 98 patients (78 men). LSBE and SSBE was diagnosed in 33 (33.7%) and 65 (66.3%) cases, respectively. VEGF was expressed in vascular endothelium of all Barrett's specimens. COX-2 and Ki-67 expression in metaplastic epithelia was strong in 81.6 and 61.2% of the samples, respectively. Ki-67 expression was significantly stronger in LSBE (p = 0.035), whereas VEGF expression was significantly increased in SSBE (p = 0.031). COX-2 expression was not associated with Barrett's length., Conclusions: VEGF, COX-2, and Ki-67 were overexpressed in the majority of Barrett's samples. The length was inversely associated with VEGF expression and directly associated with Ki-67 expression.

The hypothesis whether exposure to certain infections protects from atopy remains equivocal. To further investigate this, we compared serologic markers of infection and allergic sensitization prevalence in Roma children, who live under unfavorable hygienic conditions that facilitate the spread of infections, and non-Roma children who live in the same area. Analyses included 98 Roma and 118 non-Roma children. Serum IgG antibodies for 13 foodborne- airborne- and bloodborne infectious agents were determined, and a cumulative index of exposure was calculated by adding one point for each positive infection. Specific serum IgE to certain common food- and aero-allergens was also tested. and positivity to any of them was defined as indication of atopy. Roma children were found significantly more seropositive for T. gondii, Hepatitis A, H. pylori, HSV-1, CMV, and Hepatitis B (p < 0.0001). Non-Roma children were found more seropositive for RSV and M. pneumonia (p < 0.0001). Regarding the overall prevalence of atopy or the specific IgE responses to the allergens tested, no statistically significant differences were found between Roma and non-Roma children. A positive association of the cumulative index of exposure to infections with atopy was found in the non-Roma children (OR: 1.38, 95% CI: 1.08-1.75, p = 0.01) and in the total population (OR: 1.42, 95% CI: 1.11-1.83, p = 0.01). Regarding the specific infectious agents tested, a statistically significant positive association of atopy with seropositivity was found for M. pneumoniae in the non-Roma children (OR: 3.93, 95% CI: 1.39) as well as in the total population studied (OR: 2.83, 95% CI: 1.32-6.07, p = 0.01). Despite the higher burden of exposure to the battery of the infectious agents tested among Roma children, no protective effect for allergic disease development was evident. On the contrary, a positive association of exposure to infections with evidence of atopy was found, especially evident in the non-Roma children., (© 2010 John Wiley & Sons A/S.)

To investigate whether single nucleotide polymorphisms (SNPs) in key cytokine and innate immunity genes influence risk for childhood lymphomas, we genotyped 37 children with Hodgkin's (HL) and 48 with non-Hodgkin's lymphoma (NHL), aged (1 month-14 yr), along with their 85 age- and gender-matched controls suffering from mild medical conditions. Genotypic analysis was performed for 10 SNPs from nine genes with important role in immunoregulatory pathways (IL4, IL4R, IL6, IL10, IL12, IL18, TNFalpha, IFNgamma, CD14). Analysis of SNPs genotypes revealed that the CD14 -159 C>T polymorphism was associated with significantly increased risk for HL regarding both the CC and CT genotypes (OR(CC): 5.36; 95% CI, 1.30-22.14; P = 0.02, OR(CT): 3.76; 95% CI, 1.00-14.16; P = 0.05). An indicative association between IL18-137 G>C polymorphism with the CC genotype and NHL did not reach, however, statistical significance (OR(CC), 3.78; 95% CI, 0.87-16.38; P = 0.08). In conclusion, our findings suggest that genetic variation in the CD14-159 loci may be associated with childhood HL risk; these preliminary findings need to be further confirmed in sizeable multi-centre studies along with determination of cytokines, which could provide an insight on the biologic basis underlying these findings.