Genome-wide association study identifies novel susceptibility loci for KIT D816V positive mastocytosis.

Mastocytosis is a rare myeloid neoplasm characterized by uncontrolled expansion of mast cells, driven in >80% of affected individuals by acquisition of the KIT D816V mutation. To explore the hypothesis that inherited variation predisposes to mastocytosis, we performed a two-stage genome-wide association study, analyzing 1,035 individuals with KIT D816V positive disease and 17,960 healthy control individuals from five European populations. After quality control, we tested 592,007 SNPs at stage 1 and 75 SNPs at stage 2 for association by using logistic regression and performed a fixed effects meta-analysis to combine evidence across the two stages. From the meta-analysis, we identified three intergenic SNPs associated with mastocytosis that achieved genome-wide significance without heterogeneity between cohorts: rs4616402 (pmeta = 1.37 × 10-15, OR = 1.52), rs4662380 (pmeta = 2.11 × 10-12, OR = 1.46), and rs13077541 (pmeta = 2.10 × 10-9, OR = 1.33). Expression quantitative trait analyses demonstrated that rs4616402 is associated with the expression of CEBPA (peQTL = 2.3 × 10-14), a gene encoding a transcription factor known to play a critical role in myelopoiesis. The role of the other two SNPs is less clear: rs4662380 is associated with expression of the long non-coding RNA gene TEX41 (peQTL = 2.55 × 10-11), whereas rs13077541 is associated with the expression of TBL1XR1, which encodes transducin (ß)-like 1 X-linked receptor 1 (peQTL = 5.70 × 10-8). In individuals with available data and non-advanced disease, rs4616402 was associated with age at presentation (p = 0.009; beta = 4.41; n = 422). Additional focused analysis identified suggestive associations between mastocytosis and genetic variation at TERT, TPSAB1/TPSB2, and IL13. These findings demonstrate that multiple germline variants predispose to KIT D816V positive mastocytosis and provide novel avenues for functional investigation.

Patients with more complex ankle fractures are associated with poorer patient-reported outcome: an observational study of 11,733 patients from the Swedish Fracture Register.

BACKGROUND AND PURPOSE: Patient-reported outcome measures (PROMs) following ankle fractures, including all fracture types, have not been reported. It is therefore unclear whether fracture morphology correlates with outcome. We aimed to analyze PROMs in patients with an ankle fracture in relation to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification using population-based register data from the Swedish Fracture Register (SFR). METHODS: All patients aged ≥ 18 years with an ankle fracture (AO/OTA 44A1-C3) registered in the SFR between 2012 and 2019 were retrieved from the register. Patients with completed PROM questionnaires (Short Musculoskeletal Function Assessment and EuroQol-Visual Analogue Scale) on both day 0 (pre-trauma) and 1-year post-trauma were included. The difference in PROMs between day 0 and 1 year was calculated for each patient (delta value) and mean delta values were calculated at group level, based on the AO/OTA fracture classification. RESULTS: 11,733 patients with 11,751 fractures with complete PROMs were included. According to the AO/OTA classification, 21% were A fractures, 67% were B fractures and 12% were C fractures. All groups of patients, regardless of fracture class (A1-C3), displayed an impairment in PROMs after 1 year compared with day 0. Type C fractures displayed a larger impairment in PROMs at group level than type B, which in turn had a greater impairment than type A. The same pattern was seen in groups 3, 2, and 1 for A and B fractures. CONCLUSION: We found that the AO/OTA classification is prognostic, where more complex fractures were associated with poorer PROMs.

Methylation microarray-based detection of clinical copy-number aberrations in CLL benchmarked to standard FISH analysis.

Copy-number aberrations (CNAs) are assessed using FISH analysis in diagnostics of chronic lymphocytic leukemia (CLL), but CNAs can also be extrapolated from Illumina BeadChips developed for genome-wide methylation microarray screening. Increasing numbers of microarray data-sets are available from diagnostic samples, making it useful to assess the potential in CNA diagnostics. We benchmarked the limitations of CNA testing from two Illumina BeadChips (EPIC and 450k) and using two common packages for analysis (conumee and ChAMP) to FISH-based assessment of 11q, 13q, and 17p deletions in 202 CLL samples. Overall, the two packages predicted CNAs with similar accuracy regardless of the microarray type, but lower than FISH-based assessment. We showed that the bioinformatics analysis needs to be adjusted to the specific CNA, as no general settings were identified. Altogether, we were able to predict CNAs using methylation microarray data, however, with limited accuracy, making FISH-based assessment of deletions the superior diagnostic choice.

Phylogenetic Relationships and Next-Generation Barcodes in the Genus Torreya Reveal a High Proportion of Misidentified Cultivated Plants.

Accurate species identification is key to conservation and phylogenetic inference. Living plant collections from botanical gardens/arboretum are important resources for the purpose of scientific research, but the proportion of cultivated plant misidentification are un-tested using DNA barcodes. Here, we assembled the next-generation barcode (complete plastid genome and complete nrDNA cistron) and mitochondrial genes from genome skimming data of Torreya species with multiple accessions for each species to test the species discrimination and the misidentification proportion of cultivated plants used in Torreya studies. A total of 38 accessions were included for analyses, representing all nine recognized species of genus Torreya. The plastid phylogeny showed that all 21 wild samples formed species-specific clades, except T. jiulongshanensis. Disregarding this putative hybrid, seven recognized species sampled here were successfully discriminated by the plastid genome. Only the T. nucifera accessions grouped into two grades. The species identification rate of the nrDNA cistron was 62.5%. The Skmer analysis based on nuclear reads from genome skims showed promise for species identification with seven species discriminated. The proportion of misidentified cultivated plants from arboreta/botanical gardens was relatively high with four accessions (23.5%) representing three species. Interspecific relationships within Torreya were fully resolved with maximum support by plastomes, where Torreya jackii was on the earliest diverging branch, though sister to T. grandis in the nrDNA cistron tree, suggesting that this is likely a hybrid species between T. grandis and an extinct Torreya ancestor lineage. The findings here provide quantitative insights into the usage of cultivated samples for phylogenetic study.

Fracture pattern and risk factors for reoperation after treatment of 156 periprosthetic fractures around an anatomic cemented hip stem.

BACKGROUND AND PURPOSE: The Lubinus SP2 stem has been associated with a very low risk of periprosthetic femoral fractures (PPFFs). We aimed, primarily, to study the radiographic morphology of PPFFs close to a Lubinus SP2 stem. Secondarily, we analyzed whether higher reoperation rate was correlated to the revision method chosen or to the characteristics of the fracture and of the bone. PATIENTS AND METHODS: The study included 156 femoral fractures close to a Lubinus cemented stem. These fractures were treated in 40 hospitals in Sweden between 2006 and 2011 and were followed up until 2019. Data from the Swedish Arthroplasty Register was used. Medical records and radiographs were studied. The fractures were classified according to the Vancouver classification. The fracture location and anatomy were delineated. We also measured the remaining attachment index (RAI) and the canal thickness ratio. RESULTS: Vancouver type C (n = 101) and spiral fractures (n = 67, 41 in Vancouver C and 26 in Vancouver B) were the most common fracture types. 4 fractures were avulsion of the greater trochanter. The remaining 51 fractures occurred around the stem (B1: 25, B2: 16, and B3: 10). B fractures were more commonly reoperated on (18 of 51, 35%) than type C fractures (11 of 101, 11%, P = 0.001). In most femurs with type B3 fracture, the fracture line covered an area only around the stem, but in all B1 and in 11 of 16 B2 fractures, it was extended even distal to the stem. ORIF instead of stem revision in B2 fractures, use of short stems or plates, and inadequate reduction of the fractures were risk factors for subsequent reoperations. CONCLUSION: The higher reoperation rate in type B fractures, compared with fractures distal to the stem, could be caused by their higher degree of complexity and reduced capacity for healing in the region around the stem.

The different strategies in treating displaced femoral neck fractures: mid-term surgical outcome in a register-based cohort of 1,283 patients aged 60-69 years.

BACKGROUND AND PURPOSE: In patients around retirement age controversy exists as to whether to treat displaced femoral neck fracture (dFNF) with internal fixation (IF) or arthroplasty. An arthroplasty in this age group may need revision due to a long expected remaining lifetime. IF carries a higher risk of early failure but a maintained native hip if healing occurs. We aimed to determine the cumulative 5-year rate of conversion to arthroplasty after IF and implant revision after primary total hip arthroplasty (THA), respectively. PATIENTS AND METHODS: In this longitudinal cohort study, patients aged 60-69 years registered with a dFNF in the Swedish Fracture Register (SFR) 2012-2018 were cross-referenced with available data from the Swedish Arthroplasty Register (SAR) until December 31, 2019. Conversion to arthroplasty or revision were analyzed utilizing competing risk, with death as competing event. RESULTS: At 5 years, the cumulative rate of conversion to arthroplasty after IF was 31% (95% confidence interval [CI] 26-37). For primary THA, the 5-year rate of revision was 4.0% (CI 2.8-5.8). The 5-year mortality did not differ, being 20% (CI 16-27) and 23% (CI 20-28) after IF and THA, respectively. Regression analyses did not identify any risk factors for conversion arthroplasty based on the variables in the register. CONCLUSION: A follow-up of 5 years catches most reoperations after IF, resulting in a 31% conversion rate. The 4% revision rate at 5 years after primary THA should be seen as an intermediate result, as late complications may occur.

Treatment and outcome of AO/OTA type C distal radius fractures: 12 199 fractures from the Swedish Fracture Register.

The aim of this study was to examine the epidemiology, treatment, and patient-reported outcome of AO/OTA type C distal radius fractures (DRF) using data from a large national fracture register. We used prospectively collected data from the Swedish Fracture Register covering all AO/OTA type C DRFs registered between April 2012 and December 2018. Data on fracture type, epidemiology, trauma-mechanism, and treatment had been recorded by the treating physician. Patients had been sent an outcome questionnaire including EQ-VAS, EQ-5D, and the SMFA at the time of injury and 12 months after. A total of 12 199 cases with AO/OTA type C fracture were identified. AO/OTA type C1 fracture was most common, with 5400 cases, followed by AO type C2 with 4304 and AO/OTA type C3 with 2495. Cast treatment and surgical treatment with volar locking plate fixation were the most common treatments. Patient-reported outcome measures worsened significantly one year after the fracture, and 56% reported moderate problems with pain and discomfort one year after the fracture. Patients treated with a volar plate reported a significantly larger deterioration in EQ-5D outcome compared to patients treated with a cast. No treatment method was found to be superior. A good outcome after a type C fracture is possible, but many patients do not recover completely. Our findings indicate a relatively better self-reported outcome for patients treated with a cast, but as treatment was not randomized the clinical relevance is unclear.

IGHV-associated methylation signatures more accurately predict clinical outcomes of chronic lymphocytic leukemia patients than IGHV mutation load.

Currently, no molecular biomarker indices are used in standard care to make treatment decisions at diagnosis of chronic lymphocytic leukemia (CLL). We used Infinium MethylationEPIC array data from diagnostic blood samples of 114 CLL patients and developed a procedure to stratify patients based on methylation signatures associated with mutation load of the IGHV gene. This procedure allowed us to predict the time to treatment with a hazard ratio (HR) of 8.34 (95% confidence interval [CI]: 4.54-15.30), as opposed to a HR of 4.35 (95% CI: 2.60-7.28) using IGHV mutation status. Detailed evaluation of 17 cases for which the two classification procedures gave discrepant results showed that these cases were incorrectly classified using IGHV status. Moreover, methylation-based classification stratified patients with different overall survival (HR=1.82; 95% CI: 1.07-3.09), which was not possible using IGHV status. Furthermore, we assessed the performance of the developed classification procedure using published HumanMethylation450 array data for 159 patients for whom information on time to treatment, overall survival and relapse was available. Despite 450K array methylation data not containing all the biomarkers used in our classification procedure, methylation signatures again stratified patients with significantly better accuracy than did IGHV mutation load regarding all available clinical outcomes. Thus, stratification using IGHV-associated methylation signatures may provide better prognostic power than IGHV mutation status.

Distal radius fractures in the superelderly: an observational study of 8486 cases from the Swedish fracture register.

BACKGROUND: The distal radius fracture (DRF) is the most common fracture in adults. With an ageing population, the number of wrist fractures in the superelderly (≥ 80 years) is expected to rise. Optimal treatment for displaced DRFs remains controversial, especially in the superelderly group. In addition, basic knowledge of the outcome after a DRF in this heterogenic group is lacking. The aim of this study was to study injury characteristics, treatment and outcome of DRFs in superelderly patients using data from a large national register. METHODS: We used prospectively collected data from the Swedish Fracture Register. All distal radius fractures registered between April 2012 and December 2018 in patients ≥ 80 years of age were included. Data on epidemiology, fracture type, trauma mechanism and treatment are registered by the physician treating the patient. Patients are also sent a subjective outcome questionnaire including EQ-5D, EQ-VAS and Short Musculoskeletal Function Assessment questionnaire (SMFA-score) at the time of injury and after 12 months. The 12-month questionnaire was sent to those who had completed the questionnaire at the time of injury. A Mann-Whitney U-test was used to assess differences between treatment methods. RESULTS: Mean age for this population was 86 years (80-105 years), a majority of the patients were female (86.7%). The dominating injury mechanism was a simple fall (74.6%) in the patient's residence. The majority of fractures were AO type A (70%) followed by AO type C (20.9%) and type B (8.6%). The incidence of open fractures was significantly higher in females (2.6%) compared to males (1.5%). A majority of the fractures were treated with a cast (87.5%) with volar locking plate as the second most common treatment method (6.6%). Patient-reported outcome measures (PROMs) EQ-5D, EQ-VAS and the Arm Hand Function Index of the SMFA-score deteriorated somewhat one year after injury compared to pre-injury. PROMs did not correlate to treatment with cast or a volar plate. CONCLUSIONS: This nationwide register study provides detailed data on DRFs in the superelderly regarding epidemiology, treatment and self-reported outcome. A good self-reported outcome is possible, but many patients do not recover completely. PROMs did not correlate to type of treatment. The frequency of open fractures was significantly higher in females. The reason for this is unclear but different skin thickness in older males versus females may be one explanation.

Fractures of the lateral malleolus - a retrospective before-and-after study of treatment and resource utilization following the implementation of a structured treatment algorithm.

BACKGROUND: In 2015 a study of isolated lateral malleolar fractures (AO/OTA44-B1) treated at Sahlgrenska University hospital (SU) during two consecutive years revealed large-scale variation in the choice of treatment and planned follow-up. The study resulted in the development of a structured treatment algorithm (TA) for ankle fractures. We investigated the effects of this well-implemented TA on the classification, treatment and follow-up of lateral malleolar fractures. METHODS: The current study is an uncontrolled, non-randomized, retrospective before-and-after study comparing a group of AO/OTA44-B1 fractures treated at SU before the introduction of the TA for ankle fractures (1 April 2012 to 31 March 2014) with a group treated after the introduction of the TA (1 September 2017 to 31 August 2019). RESULTS: In all the studied parameters regarding treatment for AO/OTA44-B1 fractures, a statistically significant change was seen after the introduction of the TA. Surgical treatment reduced from 32% (95% CI 27.5 - 36.5) pre-TA to 10% (95% CI 6.9 - 13.1) post-TA, while the number of patients permitted full weight-bearing increased from 41% (95% CI 36.3 - 45.7) to 84% (95% CI 80.1 - 87.9). CONCLUSIONS: A thoroughly implemented treatment algorithm can reduce the number of surgical treatments for stable ankle fractures. The current study demonstrates that a structured treatment algorithm can standardize the management of ankle fractures and make decisions less dependent on the surgeon's discretion.

The Swedish Fracture Register - ten years of experience and 600,000 fractures collected in a National Quality Register.

BACKGROUND: Before the creation of the Swedish Fracture Register (SFR), there was no national quality register that prospectively collects data regarding all types of fractures regardless of treatment in an emergency setting. Observational data on fractures registered in a sustainable way may provide invaluable tools for quality improvements in health care and research. DESCRIPTION: Ten years after its implementation, the Swedish Fracture Register has 100% coverage among orthopaedic and trauma departments in Sweden. The completeness of registrations reached in 2020 69-96% for hip fractures at the different departments, with the majority reporting a completeness above 85%. The Swedish Fracture Register is a fully web-based national quality register created and run by orthopaedic professionals, with financial support from public healthcare providers and the government. All users have full access to both the registration platform and all aggregated statistics in real time. The web-based platform was created for use in health quality registers and it has easily gained acceptance among users. The register has gradually developed by the addition of more fracture types and skeletal parts. Research activity is high and 31 scientific publications have been published since 2016. The strategy from the start was to publish validation data and basic epidemiological data. However, over the past few years, publications on outcomes, such as re-operations and mortality, have been published and four register-based, randomised, controlled trials are ongoing. CONCLUSION: It is possible to create a fracture register, to gain professional acceptance and to collect fracture data in a sustainable way on a national level if the platform is easy to use. Such a platform can also be used as a randomisation platform for prospective studies.

Diagnosis, treatment, and outcome of primary CNS lymphoma-a single-center experience.

BACKGROUND: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) that occurs in the CNS (e.g. brain, meninges, spinal cord, cerebrospinal fluid, or intraocular involvement) in the absence of systemic NHL. Tumor resection does not improve survival, and neurosurgical intervention is generally limited to stereotactic biopsy to provide a histopathological diagnosis. OBJECTIVE: The objective of this single-center study was to evaluate the management and outcome of PCNSL patients diagnosed by biopsy, using overall survival and progression-free survival as endpoints. METHODS: At our department of neurosurgery, 140 patients were diagnosed with PCNSL by biopsy between January 1, 2009, and December 31, 2018. Of these, 37 patients were included in the study and were divided into three groups according to their postoperative therapy. RESULTS: Median OS was 35.7 months for the intensive treatment group, 29.5 months for the moderate treatment group, and 8.6 months for the palliative treatment group. The intensive and moderate treatment groups had similar progression-free survival, while the palliative treatment group had poor overall and progression-free survival. Six patients were long-term survivors (> 80 months). Age under 65 years was the main significant parameter affecting overall survival. CONCLUSION: In this cohort, patients with PCNSL had an overall fair prognosis if they (1) were under 65 years old, (2) had a performance score < 2 at the time of diagnosis, and (3) received either intensive or moderate chemotherapeutic treatment. Biopsy is still the primary diagnostic tool; other methods have been investigated but are not yet recommended.

Greater heel-rise endurance is related to better gait biomechanics in patients surgically treated for chronic Achilles tendon rupture.

PURPOSE: To determine the relationships among calf muscle function, tendon length and gait biomechanics in patients surgically treated for chronic Achilles tendon rupture. METHODS: Twenty-one patients with chronic Achilles tendon rupture (mean age 62 ± 13 years) were evaluated by heel-rise endurance test, Achilles Tendon Resting Angle (ATRA), ultrasound measurement of tendon length and three-dimensional gait analysis. A bivariate two-sided correlation test was performed on all variables in all patients. RESULTS: Better performance across all parameters of the heel-rise endurance test correlated with faster walking speed (r = 0.52-0.55), greater peak ankle power (r = 0.56-0.64), shorter stance phase (r = -0.52 to -0.76) and less peak ankle dorsiflexion angle (r = -0.49 to -0.64) during gait. Greater ATRA correlated with longer stance time (r = 0.47), greater peak ankle dorsiflexion angle (r = 0.48), less heel-rise repetitions (r = -0.52) and less heel-rise total work LSI (r = -0.44 to -0.59). CONCLUSION: Greater calf muscle endurance, especially heel-rise total work, is moderately correlated (r = 0.49-0.76) to better ankle biomechanics during gait in patients surgically treated for CATR. The heel-rise endurance test may be a clinical proxy for power development in the ankle joint during gait. LEVEL OF EVIDENCE: IV.

Allopatric Lineage Divergence of the East Asian Endemic Herb Conandron ramondioides Inferred from Low-Copy Nuclear and Plastid Markers.

The evolutionary histories of ornamental plants have been receiving only limited attention. We examined the origin and divergence processes of an East Asian endemic ornamental plant, Conandron ramondioides. C. ramondioides is an understory herb occurring in primary forests, which has been grouped into two varieties. We reconstructed the evolutionary and population demography history of C. ramondioides to infer its divergence process. Nuclear and chloroplast DNA sequences were obtained from 21 Conandron populations on both sides of the East China Sea (ECS) to explore its genetic diversity, structure, and population differentiation. Interestingly, the reconstructed phylogeny indicated that the populations should be classified into three clades corresponding to geographical regions: the Japan (Honshu+Shikoku) clade, the Taiwan-Iriomote clade, and the Southeast China clade. Lineage divergence between the Japan clade and the Taiwan-Iriomote and Southeast China clades occured 1.14 MYA (95% HPD: 0.82-3.86), followed by divergence between the Taiwan-Iriomote and Southeast China clades approximately 0.75 MYA (95% HPD: 0.45-1.3). Furthermore, corolla traits (floral lobe length to tube length ratios) correlated with geographical distributions. Moreover, restricted gene flow was detected among clades. Lastly, the lack of potential dispersal routes across an exposed ECS seafloor during the last glacial maximum suggests that migration among the Conandron clades was unlikely. In summary, the extant Conandron exhibits a disjunct distribution pattern as a result of vicariance rather than long-distance dispersal. We propose that allopatric divergence has occurred in C. ramondioides since the Pleistocene. Our findings highlight the critical influence of species' biological characteristics on shaping lineage diversification of East Asian relic herb species during climate oscillations since the Quaternary.

Rate of conversion to secondary arthroplasty after femoral neck fractures in 796 younger patients treated with internal fixation: a Swedish national register-based study.

BACKGROUND AND PURPOSE: In younger patients with a femoral neck fracture (FNF), internal fixation is the recommended treatment regardless of displacement. Healing complications are often treated with arthroplasty. We determined the rate of conversion to arthroplasty up to 5 years after fixation of either undisplaced FNFs (uFNFs) or displaced FNFs (dFNFs). PATIENTS AND METHODS: The study was based on prospectively collected data from the Swedish Fracture Register (SFR) and the Swedish Arthroplasty Register (SAR). FNFs in patients aged < 60 treated with parallel pins/screws or sliding hip screws (SHS) registered in SFR 2012-2018 were cross-referenced with conversions to arthroplasty registered in SAR until 2019. The cumulative conversion and mortality rates were determined by Kaplan-Meier analyses and patient- and surgery-dependent risk factors for conversion by Cox regression analyses. RESULTS: We included 407 uFNFs and 389 dFNFs (median age 52, 59% men). The 1-year conversion rate was 3% (95% CI 1-5) for uFNFs and 9% (CI 6-12) for dFNFs. Corresponding results at 5 years were 8% (CI 5-11) and 25% (CI 20-30). Besides a displaced fracture, age 50-59 was associated with an increased rate of conversion in uFNFs. This older group also had a higher mortality rate, compared with patients aged < 50. There was no sex difference for mortality. INTERPRETATION: Adults aged under 60 with uFNFs and dFNFs face an 8-25% risk, respectively, of conversion to arthroplasty within 5 years after internal fixation. This is new and pertinent information for surgeons as well as patients.

Surveillance of atypical femoral fractures in a nationwide fracture register.

Background and purpose - To continuously assess the incidence of atypical femoral fractures (AFFs) in the population is important, to allow the evaluation of the risks and benefits associated with osteoporosis treatment. Therefore, we investigated the possibility to use the Swedish Fracture Register (SFR) as a surveillance tool for AFFs in the population and to explore means of improvement. Patients and methods - All AFF registrations in the SFR from January 1, 2015 to December 31, 2018 were enrolled in the study. For these patients, radiographs were obtained and combined with radiographs from 176 patients with normal femoral fractures, to form the study cohort. All images were reviewed and classified into AFFs or normal femur fractures by 2 experts in the field (gold-standard classification) and 1 orthopedic resident educated on the specific radiographic features of AFF (educated-user classification). Furthermore, we estimated the incidence rate of AFFs in the population captured by the register through comparison with a previous cohort and calculated the positive predictive value (PPV) and, where possible, the inter-observer agreement (Cohen's kappa) between the different classifications. Results - Of the 178 available patients with AFF in the SFR, 104 patients were classified as AFF using the goldstandard classification, and 89 using the educated-user classification. The PPV increased from 0.58 in the SFR classification to 0.93 in the educated-user classification. The interobserver agreement between the gold-standard classification and the educated-user classification was 0.81. Interpretation - With a positive predictive value of 0.58 the Swedish Fracture Register outperforms radiology reports and reports to the Swedish Medical Products Agency on adverse drug reactions as a diagnostic tool to identify atypical femoral fractures.

Increased mortality after intramedullary nailing of trochanteric fractures: a comparison of sliding hip screws with nails in 19,935 patients.

Background and purpose - Intramedullary nails (IMN) have become increasingly common as treatment for trochanteric hip fractures (THF) although they are costlier, and without proven superiority compared with sliding hip screws (SHS). We investigated whether the 2 methods differ in terms of short-term mortality when used in fractures where both methods are suitable. Patients and methods - We extracted data from the Swedish Fracture Register (SFR) on 19,935 patients ≥ 60 years with trochanteric fractures AO type 31-A1 or -A2 who had been treated with either SHS or IMN. We assessed absolute mortality rates and the relative risks (RR) of death after 7, 30, 90, and 365 days using generalized linear models, adjusting for age, sex, and fracture type. We performed a sensitivity analysis on a subgroup of 3,673 patients with information on comorbidity to address this potential confounder. Results - 69% of the patients were women and mean age was 84 years (60-107). IMN was used in 35% of A1 and in 71% of A2 fractures. The use of IMN was associated with a slightly increased adjusted risk of death within 30 days compared with SHS (RR = 1.1, 95% CI 1.0-1.2) with no difference at any other time point. Interpretation - The slightly increased risk of death up to 30 days postoperatively does not support the use of IMN instead of SHS in stable THF.

Stress fractures of the femoral neck in adults: an observational study on epidemiology, treatment, and reoperations from the Swedish Fracture Register.

BACKGROUND AND PURPOSE: Stress fractures of the femoral neck (sFNFs) are uncommon injuries. Studies on sFNFs are rare. We describe the demographics, classification, treatment, reoperation rates, and mortality in a cohort of sFNF patients from the Swedish Fracture Register (SFR). PATIENTS AND METHODS: We included 146 patients ≥ 18 years of age with an sFNF registered in the SFR between 2011 and 2020. The cohort was linked with the Swedish Arthroplasty Register and reviewed using medical records and radiographs. We assessed the presence of disorders of bone remodeling, duration of symptoms, fracture classification, treatment, reoperations, and mortality. RESULTS: The mean age was 58 years (21-96), 75% were women and the median duration of symptoms was 23 days (1-266). 40% of patients had disorders of bone remodeling. 54% were undisplaced (uFNF), 30% displaced (dFNF), and 16% basicervical (bFNF). 14% of patients < 60 years were treated nonoperatively, by internal fixation (IF) in 77% and by arthroplasty in 10%. Patients ≥ 60 years were treated nonoperatively in 10%, IF in 40%, and arthroplasty in 49%. Nonoperative treatment was reserved for uFNFs or bFNFs, resulting in 35% receiving late surgery. The overall secondary or late surgery rate was 19%. Mortality was 2% at 90 days and increased to 3% at 1 year. INTERPRETATION: sFNF has a biphasic age distribution. One-third of patients presented with a displaced FNF and those managed nonoperatively for an undisplaced sFNF were at risk of late surgery. The mortality rates for patients with these injuries was low.

Study protocol: The DAICY trial-dual versus single-antibiotic impregnated cement in primary hemiarthroplasty for femoral neck fracture-a register-based cluster-randomized crossover-controlled trial.

BACKGROUND AND PURPOSE: Older patients with a displaced femoral neck fracture (FNF) are often treated with a cemented primary hemiarthroplasty (HA). The DAICY trial investigates whether high-dose dual-impregnated antibioticloaded cement (DIAC) including gentamicin and clindamycin can reduce the risk of periprosthetic joint infection (PJI) in comparison with low-dose single-impregnated gentamicin antibiotic-loaded cement (SIAC), in patients ≥ 60 years treated with a cemented HA for a displaced FNF. STUDY DESIGN: The trial is a national, multicenter, register-based, cluster-randomized, crossover trial. Patients ≥ 60 years with a non-pathological, displaced FNF (Type Garden 3-4/AO 31-B2 or B3) suitable for HA according to local guidelines are eligible for inclusion. Participating orthopedic departments will be randomized to start with either SIAC (control group) or DIAC treatment (intervention group) for 2 years. After 2 years, the study departments will then change to the other treatment arm for the remaining 2 years of the study. Approximately 7,000 patients will be included. The study is pragmatic in that the choice of implant brands, surgical approach and peri- and postoperative protocols follow the local routines of each participating department. All outcome variables will be retrieved after linkage of the study cohort to the following Swedish registers: the Fracture Register, the Arthroplasty Register, the National Patient Register and the Prescribed Drug Registry Outcome: The primary outcome will be periprosthetic joint infection of the index joint within 1 year after surgery. Secondary outcomes will be any reoperation on the index joint, mortality within 90 days and 1 year, resistance patterns of causative bacteria in cases of PJI, and health economics. Potential added value: This trial is designed to support or refute the efficacy of DIAC used in patients with a displaced FNF, potentially reducing PJI and resource allocation. Start of the trial and estimated duration - The DAICY trial started recruiting patients in January 2022 and will continue recruiting for approximately 4 years. Complete follow-up expected in 5 years.

Epidemiology, classification, treatment and mortality of Talus fractures: An observational study of 1794 talus fractures from the Swedish Fracture Register.

BACKGROUND: Epidemiological data on talus fractures from large nationwide and multicenter studies are rare. This study aims to describe the epidemiology, fracture classification and treatment regimens of talus fractures in a large adult Swedish population. METHODS: This observational study is based on data from the Swedish Fracture Register (SFR) including talar fractures in patients ≥18 with a sustained fracture between 2012 and 2021. Epidemiological data on sex, age, injury date, injury mechanism and type (high or low energy trauma), fracture classification (side, type), initial treatment and mortality were analysed. RESULTS: We included 1794 talus fractures (1757 patients, 60 % men). Mean age was 40.3 years (range 18-96), and a biphasic age distribution was seen in women. High-energy trauma caused 33 % of all talus fractures. Of all talus fractures, 817 (45.5 %) were classified as AO/OTA type A fractures (avulsion), 370 (20.6 %) as type B (neck) and 435 (24.2 %) as type C (body). The remaining 172 (9.6 %) talus fractures were not classified/unclassifiable. Men were in the majority in all fracture groups except A1. For type A1-3, B1 and C1-2 fractures, most patients were treated non-operatively; in B2-3 and C3 fractures most patients received operative management. Fracture fixation with screws was the dominating surgical treatment. The overall 30-day mortality was 0.2 %. CONCLUSION: Talus fractures are most commonly encountered in young and middle-aged men. In contrast to men, a biphasic age distribution was observed in women. Approximately half of the talus fractures are avulsions. Operative treatment, mostly screw fixation, is performed in more complex fracture configurations (B2, B3 and C3 fractures). LEVEL OF EVIDENCE: IV, retrospective observational cohort study.