Reamed locked intramedullary nailing for studying femur fracture and its complications.

Morbidity associated with femur fractures in polytrauma patients is known to be high. The many unsolved clinical questions include the immunological effect of the fracture and its fixation, timing of fracture fixation, management of fracture non-union, effect of infection and critical size of bone defects. The aim of this study was to establish a clinically-relevant and reproducible animal model with regards to histological, biomechanical and radiological changes during bone healing. A custom-designed intramedullary nail with interlocking system (RabbitNail, RISystem AG, Davos Platz, Switzerland) was used for fixation, following femur fracture. New Zealand White rabbits were assigned to two groups: 1. closed fracture model (CF; non-survival model: n = 6, survival model: n = 3) with unilateral mid-shaft femur fracture created by blunt force; 2. osteotomy model (OT; survival model: n = 14) with unilateral transverse osteotomy creating femur fracture. There were no intraoperative complications and full-weight bearing was achieved in all survival rabbits. Significant periosteal reaction and callus formation were confirmed from 2 weeks postoperatively, with a significant volume formation (739.59 ± 62.14 mm3) at 8 weeks confirmed by micro-computed tomography (µ-CT). 2 months after fixation, there was no difference between the osteotomised and contralateral control femora in respect to the maximum torque (3.47 ± 0.35 N m vs. 3.26 ± 0.37 N m) and total energy (21.11 ± 3.09 N m × degree vs. 20.89 ± 2.63 N m × degree) required to break the femur. The data confirmed that a standardised internal fixation technique with an intramedullary nail for closed fracture or osteotomy produced satisfactory bone healing. It was concluded that important clinically-relevant studies can be conducted using this rabbit model.

Seeking the driver in tumours with apparent normal molecular profile on comparative genomic hybridization and targeted gene panel sequencing: what is the added value of whole exome sequencing?

BACKGROUND: Molecular tumour profiling technologies have become increasingly important in the era of precision medicine, but their routine use is limited by their accessibility, cost, and tumour material availability. It is therefore crucial to assess their relative added value to optimize the sequence and combination of such technologies. PATIENTS AND METHODS: Within the MOSCATO-01 trial, we investigated the added value of whole exome sequencing (WES) in patients that did not present any molecular abnormality on array comparative genomic hybridization (aCGH) and targeted gene panel sequencing (TGPS) using cancer specific panels. The pathogenicity potential and actionability of mutations detected on WES was assessed. RESULTS: Among 420 patients enrolled between December 2011 and December 2013, 283 (67%) patients were analysed for both TGPS and aCGH. The tumour sample of 25 (8.8%) of them presented a flat (or low-dynamic) aCGH profile and no pathogenic mutation on TGPS. We selected the first eligible 10 samples-corresponding to a heterogeneous cohort of different tumour types-to perform WES. This allowed identifying eight mutations of interest in two patients: FGFR3, PDGFRB, and CREBBP missense single-nucleotide variants (SNVs) in an urothelial carcinoma; FGFR2, FBXW7, TP53, and MLH1 missense SNVs as well as an ATM frameshift mutation in a squamous cell carcinoma of the tongue. The FGFR3 alteration had been previously described as an actionable activating mutation and might have resulted in treatment by an FGFR inhibitor. CREBBP and ATM alterations might also have suggested a therapeutic orientation towards epigenetic modifiers and ataxia-telangectasia and Rad3-related inhibitors, respectively. CONCLUSION: The therapeutic added value of performing WES on tumour samples that do not harbour any genetic abnormality on TGPS and aCGH might be limited and variable according to the histotype. Alternative techniques, including RNASeq and methylome analysis, might be more informative in selected cases.

Vascular endothelial growth factor levels in tears of patients with retinal vein occlusion.

PURPOSE: We measured vascular endothelial growth factor (VEGF) levels in tear fluid and serum in patients with retinal vein occlusion (RVO). PATIENTS AND METHODS: Eight patients with RVO due to secondary macular oedema were examined. VEGF levels were measured by enzyme-linked immunosorbent assay. All patients had a full ophthalmic examination (visual acuity, slit lamp biomicroscopy, perimetry, and fluorescein angiography). Central retinal thickness (CRT) was examined using optical coherence tomography (OCT). Tear and serum samples were collected and examinations were performed at diagnosis and 1 and 4 weeks later. RESULTS: VEGF levels in the tears of RVO eyes were significantly higher than in fellow eyes at diagnosis and after both 1 and 4 weeks (paired t test, p1 = 0.01, p2 = 0.02, p3 = 0.006). We found a weak but significant positive correlation between VEGF levels in tear fluid and serum of patients with RVO (r = 0.21), while this correlation tended to be stronger between the fellow eyes and serum levels (r = 0.33). CONCLUSION: To the best of our knowledge, we are the first to report an increased level of VEGF in the tear fluid of patients with RVO. Alterations of VEGF levels in tears may be useful for determining stages of RVO. This non-invasive and objective method may also be helpful for estimating the severity of macular oedema and efficacy of treatment.

Damage control surgery for abdominal emergencies.

BACKGROUND: Damage control surgery is a management sequence initiated to reduce the risk of death in severely injured patients presenting with physiological derangement. Damage control principles have emerged as an approach in non-trauma abdominal emergencies in order to reduce mortality compared with primary definitive surgery. METHODS: A PubMed/MEDLINE literature review was conducted of data available over the past decade (up to August 2013) to gain information on current understanding of damage control surgery for abdominal surgical emergencies. Future directions for research are discussed. RESULTS: Damage control surgery facilitates a strategy for life-saving intervention for critically ill patients by abbreviated laparotomy with subsequent reoperation for delayed definitive repair after physiological resuscitation. The six-phase strategy (including damage control resuscitation in phase 0) is similar to that for severely injured patients, although non-trauma indications include shock from uncontrolled haemorrhage or sepsis. Minimal evidence exists to validate the benefit of damage control surgery in general surgical abdominal emergencies. The collective published experience over the past decade is limited to 16 studies including a total of 455 (range 3-99) patients, of which the majority are retrospective case series. However, the concept has widespread acceptance by emergency surgeons, and appears a logical extension from pathophysiological principles in trauma to haemorrhage and sepsis. The benefits of this strategy depend on careful patient selection. Damage control surgery has been performed for a wide range of indications, but most frequently for uncontrolled bleeding during elective surgery, haemorrhage from complicated gastroduodenal ulcer disease, generalized peritonitis, acute mesenteric ischaemia and other sources of intra-abdominal sepsis. CONCLUSION: Damage control surgery is employed in a wide range of abdominal emergencies and is an increasingly recognized life-saving tactic in emergency surgery performed on physiologically deranged patients.

Characterization of Eyjafjallajokull volcanic ash particles and a protocol for rapid risk assessment.

On April 14, 2010, when meltwaters from the Eyjafjallajökull glacier mixed with hot magma, an explosive eruption sent unusually fine-grained ash into the jet stream. It quickly dispersed over Europe. Previous airplane encounters with ash resulted in sandblasted windows and particles melted inside jet engines, causing them to fail. Therefore, air traffic was grounded for several days. Concerns also arose about health risks from fallout, because ash can transport acids as well as toxic compounds, such as fluoride, aluminum, and arsenic. Studies on ash are usually made on material collected far from the source, where it could have mixed with other atmospheric particles, or after exposure to water as rain or fog, which would alter surface composition. For this study, a unique set of dry ash samples was collected immediately after the explosive event and compared with fresh ash from a later, more typical eruption. Using nanotechniques, custom-designed for studying natural materials, we explored the physical and chemical nature of the ash to determine if fears about health and safety were justified and we developed a protocol that will serve for assessing risks during a future event. On single particles, we identified the composition of nanometer scale salt coatings and measured the mass of adsorbed salts with picogram resolution. The particles of explosive ash that reached Europe in the jet stream were especially sharp and abrasive over their entire size range, from submillimeter to tens of nanometers. Edges remained sharp even after a couple of weeks of abrasion in stirred water suspensions.

Configuration-Specific Insight into Single-Molecule Conductance and Noise Data Revealed by the Principal Component Projection Method.

We explore the merits of neural network boosted, principal-component-projection-based, unsupervised data classification in single-molecule break junction measurements, demonstrating that this method identifies highly relevant trace classes according to the well-defined and well-visualized internal correlations of the data set. To this end, we investigate single-molecule structures exhibiting double molecular configurations, exploring the role of the leading principal components in the identification of alternative junction evolution trajectories. We show how the proper principal component projections can be applied to separately analyze the high- or low-conductance molecular configurations, which we exploit in 1/f-type noise measurements on bipyridine molecules. This approach untangles the unclear noise evolution of the entire data set, identifying the coupling of the aromatic ring to the electrodes through the π orbitals in two distinct conductance regions, and its subsequent uncoupling as these configurations are stretched.

Impact of comorbidities on survival following major injury across different types of road users.

BACKGROUND: While comorbidities and types of road users are known to influence survival in people hospitalised with injury, few studies have examined the association between comorbidities and survival in people injured in road traffic crashes. Further, few studies have examined outcomes across different types of road users with different types of pre-existing comorbidities. This study aims to examine differences in survival within 30 days of admission among different road user types with and without different pre-existing comorbidities. METHOD: Retrospective cohort study using data for all major road trauma cases were extracted from the NSW Trauma Registry Minimum Dataset (1 January 2013 - 31 July 2019) and linked to the NSW Admitted Patient Data Collection, and the NSW Registry of Births, Deaths and Marriages - death dataset. Pre-existing comorbidities and road user types were identified by the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes and Charlson Comorbidity Index in the Trauma Registry, hospital admission, and death datasets. Logistic regression was used to assess the associations between six types of road users (pedestrian, pedal cycle, two- and three-wheel motorcycle, car and pick-up truck, heavy vehicle and bus, and other types of vehicle) and death within 30 days of hospital admission while controlling for comorbidities. All models used 'car and pick-up truck driver/passenger' as the road user reference group and adjusted for demographic variables, injury severity, and level of impaired consciousness. RESULTS: Within 6253 traffic injury person-records (all aged ≥15 years old, ISS>12), and in final models, injured road users with major trauma who had a history of cardiovascular diseases (including stroke), diabetes mellitus, and higher Charlson Comorbidity Index score, were more likely to die, than those without pre-existing comorbidities. Furthermore, in final models, pedestrians were more likely to die than car occupants (OR: 1.68 - 1.77, 95CI%: 1.26 - 2.29 depending on comorbidity type). CONCLUSIONS: This study highlights the need to prioritize enhanced management of trauma patients with comorbidities, given the increasing prevalence of chronic medical conditions globally, together with actions to prevent pedestrian crashes in strategies to reach Vision Zero.

Structural Memory Effects in Gold-4,4'-Bipyridine-Gold Single-Molecule Nanowires.

We study the vulnerability of single-molecule nanowires against a temporary disconnection of the junction. To this end, we compare the room and low-temperature junction formation trajectories along the opening and closing of gold-4,4'-bipyridine-gold single-molecule nanowires. In the low-temperature measurements, the cross-correlations between the opening and subsequent closing conductance traces demonstrate a strong structural memory effect: around half of the molecular opening traces exhibit similar, statistically dependent molecular features as the junction is closed again. This means that the junction stays rigid and the molecule remains protruding from one electrode even after the rupture of the junction, and therefore, the same single-molecule junction can be reestablished if the electrodes are closed again. In the room-temperature measurements, however, weak opening-closing correlations are found, indicating a significant rearrangement of the junction after the rupture and the related loss of structural memory effects.

The morphology of ligamentous sacroiliac lesions - challenge to the antero-posterior compression mechanism.

AIM: This paper evaluates computer tomographic morphology of partial ligamentous lesions of the sacroiliac joint. We hypothesised that in antero-posterior compression (APC) injuries the anterior superior portion of the sacroiliac joint (SIJ) should open up the most as suggested by the vector forces outlined in the Young and Burgess classification. METHODS: All patients who underwent operative fixation of a ligamentous APC pelvic injury between July 2009 and December 2015 in a single Level-1 trauma centre were included. Patients were case matched (1:1) to controls without pelvic injury. SIJ width was measured by two independent reviewers at the anterior superior and anterior inferior part of the SIJ. Wilcoxon ranged test was applied for analysis. RESULTS: 70 patients (35 cases, 35 controls) were evaluated. Median inferior and superior SI joint widths were 5.27 (IQR 3.68-7.80) and 4.05 (IQR 3.13-5.31) mm in cases versus 2.24 (IQR 1.83-2.50) and 2.44 (IQR 2.14-2.65) mm in controls, respectively. The difference between the inferior and superior SI width in cases was larger than in controls (p-value < 0.01, median of -0.22 mm in the control group versus 1.51 mm in the cases). CONCLUSION: Our data suggests that the inferior part of the SIJ opens up after injury more, relative to its superior portion. The vector of the force involved in rotationally unstable pelvic injuries is unlikely to be antero-posterior if the force causes the SI joint to widen up inferiorly first. This should be considered in SIJ fixation and challenges the APC mechanism in pure ligamentous rotationally unstable pelvic ring injuries.

Heart failure with preserved ejection fraction or non-cardiac dyspnea in paroxysmal atrial fibrillation: The role of left atrial strain.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea and paroxysmal atrial fibrillation (AF) is challenging. Speckle tracking-derived left atrial strain (LAS) provides an accurate estimate of left ventricular (LV) filling pressures and left atrial (LA) phasic function. However, data on clinical utility of LAS in patients with dyspnea and AF are scarce. OBJECTIVE: To assess relationship between the LAS and the probability of HFpEF in patients with dyspnea and paroxysmal AF. METHODS: The study included 205 consecutive patients (62 ± 10 years, 58% males) with dyspnea (NYHA≥II), paroxysmal AF and preserved LV ejection fraction (≥50%), who underwent speckle tracking echocardiography during sinus rhythm. Probability of HFpEF was estimated using H2FPEF and HFA-PEFF scores, which combine clinical characteristics, echocardiographic parameters and natriuretic peptides. RESULTS: Patients with high probability of HFpEF were significantly older, had higher body mass index, NT-proBNP, E/e', pulmonary artery pressure and larger LA volume index than patients in low-to-intermediate probability groups (all p < 0.05). All components of LAS and LA strain rate showed proportional impairment with increasing probability of HFpEF (all p < 0.05). Out of the speckle tracking-derived parameters, reservoir LAS showed the largest area under the curve (AUC = 0.78, p < 0.001) and the strongest independent predictive value (OR: 1.22, 95% CI 1.08-1.38) to identify patients with high probability of HFpEF. CONCLUSIONS: Reservoir LAS shows a high diagnostic performance to distinguish HFpEF from non-cardiac causes of dyspnea in symptomatic patients with paroxysmal AF.

Voltage-Controlled Binary Conductance Switching in Gold-4,4'-Bipyridine-Gold Single-Molecule Nanowires.

We investigate gold-4,4'-bipyridine-gold single-molecule junctions with the mechanically controllable break junction technique at cryogenic temperature (T = 4.2 K). We observe bistable probabilistic conductance switching between the two molecular binding configurations, influenced both by the mechanical actuation and by the applied voltage. We demonstrate that the relative dominance of the two conductance states is tunable by the electrode displacement, whereas the voltage manipulation induces an exponential speedup of both switching times. The detailed investigation of the voltage-tunable switching rates provides an insight into the possible switching mechanisms.

Role of HLA-DRB1 and PTPN22 genes in susceptibility to juvenile idiopathic arthritis in Hungarian patients.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a complex immune-mediated disease characterized by environmental influences along with several predisposing genes in the pathogenesis. The present study was undertaken to investigate the association of polymorphisms in two candidate genes for autoimmunity, human leukocyte antigen (HLA) DRB1 and protein tyrosine phosphatase N22 (PTPN22) with JIA in Hungarian patients. METHODS: A case-control study including 150 Hungarian JIA patients and 200 sex and ethnically matched healthy controls was conducted. Genotyping for HLA-DRB1 and PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601) was carried out by group-specific PCR amplification and by real-time PCR allelic discrimination, respectively. RESULTS: In Hungarian patients JIA was associated with HLA-DRB1*01, DRB1*08, DRB1*13 (p=0.048, p=0.002, p=0.019, respectively) with marked differences between the disease subtypes classified according to the ILAR criteria. There was no association of the PTPN22 C1858T SNP with JIA (p=0.66). No correlation was found between the presence of this PTPN22 SNP and HLA-DRB1 alleles. CONCLUSIONS: Our results confirm that certain HLA-DRB1 alleles reported previously as susceptibility factors are strongly associated with JIA in a Hungarian population. However, C1858T polymorphism of PTPN22, another candidate gene of autoimmunity seems to be independent of JIA in Hungarian patients. Our data taken together with various findings in different populations suggest that associations related to PTPN22 seem to be more ethnicity-specific in contrast to the general and less population-dependent role of HLA-DRB1 in JIA.

An interobserver reliability comparison between the Orthopaedic Trauma Association's open fracture classification and the Gustilo and Anderson classification.

AIMS: To evaluate interobserver reliability of the Orthopaedic Trauma Association's open fracture classification system (OTA-OFC). PATIENTS AND METHODS: Patients of any age with a first presentation of an open long bone fracture were included. Standard radiographs, wound photographs, and a short clinical description were given to eight orthopaedic surgeons, who independently evaluated the injury using both the Gustilo and Anderson (GA) and OTA-OFC classifications. The responses were compared for variability using Cohen's kappa. RESULTS: The overall interobserver agreement was ĸ = 0.44 for the GA classification and ĸ = 0.49 for OTA-OFC, which reflects moderate agreement (0.41 to 0.60) for both classifications. The agreement in the five categories of OTA-OFC was: for skin, ĸ = 0.55 (moderate); for muscle, ĸ = 0.44 (moderate); for arterial injury, ĸ = 0.74 (substantial); for contamination, ĸ = 0.35 (fair); and for bone loss, ĸ = 0.41 (moderate). CONCLUSION: Although the OTA-OFC, with similar interobserver agreement to GA, offers a more detailed description of open fractures, further development may be needed to make it a reliable and robust tool. Cite this article: Bone Joint J 2018;100-B:242-6.

The effect of haemorrhagic shock and resuscitation on fracture healing in a rabbit model: an animal study.

Aims: Little is known about the effect of haemorrhagic shock and resuscitation on fracture healing. This study used a rabbit model with a femoral osteotomy and fixation to examine this relationship. Materials and Methods: A total of 18 male New Zealand white rabbits underwent femoral osteotomy with intramedullary fixation with 'shock' (n = 9) and control (n = 9) groups. Shock was induced in the study group by removal of 35% of the total blood volume 45 minutes before resuscitation with blood and crystalloid. Fracture healing was monitored for eight weeks using serum markers of healing and radiographs. Results: Four animals were excluded due to postoperative complications. The serum concentration of osteocalcin was significantly elevated in the shock group postoperatively (p < 0.0001). There were otherwise no differences with regard to serum markers of bone healing. The callus index was consistently increased in the shock group on anteroposterior (p = 0.0069) and lateral (p = 0.0165) radiographs from three weeks postoperatively. The control group showed an earlier decrease of callus index. Radiographic scores were significantly greater in the control group (p = 0.0025). Conclusion: In a rabbit femoral osteotomy model with intramedullary fixation, haemorrhagic shock and resuscitation produced larger callus but with evidence of delayed remodelling. Cite this article: Bone Joint J 2018;100-B:1234-40.

Richter's and prolymphocytic transformation of chronic lymphocytic leukemia are associated with high mRNA expression of activation-induced cytidine deaminase and aberrant somatic hypermutation.

Chronic lymphocytic leukemia (CLL) is an indolent B-cell non-Hodgkin's lymphoma that may transform into higher-grade lymphoma. The transformation involves an increased number of prolymphocytic cells, termed prolymphocytic transformation (PLT) or the development of diffuse large B-cell lymphoma (DLBL), also referred to as Richter's transformation (RT). To analyze whether activation-induced cytidine deaminase (AID), which is essential for somatic hypermutation (SHM) of normal B-cells, and malfunction of SHM termed aberrant somatic hypermutation (ASHM) are associated with higher-grade transformation of CLL, AID mRNA expression and the mutation pattern of c-MYC, PAX-5 and RhoH genes were analyzed in eight cases of CLL without transformation and in 21 cases that showed RT or PLT. Chronic lymphocytic leukemia cases, which showed no transformation or eventually transformed into higher-grade lymphoma, showed low levels of AID mRNA expression and low frequency of mutations of c-MYC, PAX-5 and RhoH genes. In both RT and PLT, high-levels of AID mRNA expression and high-frequency mutations of c-MYC, PAX-5 and RhoH genes were detected. These results indicate that AID expression and ASHM are associated with higher-grade transformation of CLL and provide further evidences that AID expression and ASHM may be activated during the clonal history of B-cell lymphomas.

Spontaneous recanalization in deep venous thrombosis: a prospective duplex ultrasound study.

AIM: The aim of this study was to evaluate the dynamics of the recanalization process (spontaneous fibrinolysis) in completely occlusive deep venous thrombosis (DVT) using duplex ultrasound examination and to investigate the influence of different factors on the evolution of thrombus regression. METHODS: This longitudinal prospective study was done with 74 consecutive patients with completely occlusive acute multilevel DVT, confirmed by echo duplex scan after 1, 3, 6, and 12 months. At each re-evaluation, the degree and the type of recanalization were determined. Efficacy of tinzaparin (175 IU/kg, s.c., q.d. for 7-14 days) and continued with warfarin (12 months at INR 2-3) as well as patients' compliance with compressive elastic hosiery wearing were carefully followed. Relationship between the degree and pattern of recanalization and patients' age, gender, as well as thrombosis etiology and location were determined. RESULTS: Sixty-four patients completed the study. The mean recanalization rate was 39.7% at 1, 64.8% at 3, 82% at 6, and 90.3% at 12 months. Marginal recanalization was more frequently observed, but recanalization pattern was changing during follow-up. CONCLUSIONS: In the case of efficient anticoagulant and compressive therapy, the spontaneous recanalization process of DVT is important from the very first month of evolution, but an almost complete re-permeabilization is observed only after 12 months of treatment. The unilocular, marginal pattern of thrombus lysis is often observed and has better evolution than the multilocular cavernous one. The dynamics of recanalization are characterized by distal-to-proximal extension and in the first 6 months are significantly influenced by patient's gender and thrombosis etiology.

Erratum to: The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections.

[This corrects the article DOI: 10.1186/s13017-017-0141-6.].

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

National registry of patients with juvenile idiopathic inflammatory myopathies in Hungary--clinical characteristics and disease course of 44 patients with juvenile dermatomyositis.

Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by chronic muscle inflammation resulting in progressive weakness and frequent involvement of internal organs, mainly the pulmonary, gastrointestinal and cardiac systems which considerably contribute to the morbidity and mortality of the IIMs. Aim of this study was to present clinical characteristics, disease course, frequency of relapses and survival in patients with juvenile dermatomyositis (DM). A national registry of patients with juvenile IIMs was elaborated by the authors in Hungary. We have summarized data of the register according to signs and symptoms, disease course, frequency of relapses and survival of patients with juvenile IIM. Analysis was performed using data of 44 patients with juvenile DM diagnosed between 1976 and 2004 according to Bohan and Peter's criteria. Survival probability was calculated by Kaplan-Meier method. Data of patients with juvenile DM were compared with data of 66 patients with adult DM. The most frequent cutaneous features were facial erythema and heliotrope rash. Extramuscular and extraskeletal manifestations of the disease were more frequent in adult patients. The most common extramuscular feature was arthralgia in both groups of patients with juvenile or adult DM. Cardiac manifestation of the disease was not observed in juvenile patients. Respiratory muscle involvement and interstitial lung disease (ILD) were more frequent among adult DM patients than cardiac manifestation of the myositis. In view of the disease course, the authors found that frequency of polycyclic and monophasic subtypes of the disease were mainly similar. The hazard of relapse was found higher during the first year after the remission. None of the juvenile patients died. Among adult patients four disease-specific deaths occurred. There was no correlation between relapse free survival and initial therapeutic regimen. Many of our patients had polycyclic or chronic disease. As relapses can occur after a prolonged disease-free interval, patients should be followed up for at least 2 years. Although we found favourable survival probability, further investigations are needed to assess functional outcome.