Blood Management in a Liver Transplant Recipient with Kidd (Jka) and Rhesus (D) Antibodies: A Case Report.

A 67-year-old man presented for urgent liver transplantation (LT). Screening revealed the rare combination of antiRhesus (D) and antiKidd Jk(a) antibodies, requiring antigen-negative red blood cells (RBC) for both phenotypes. This combination has not been reported during LT. Compatible RBCs were initially limited, requiring continued communication between the blood bank/blood supplier to obtain more, including frozen, units. Additional strategies included the use of cell salvage and intentional management of coagulopathy to limit bleeding and RBC requirement. This case highlights blood management during LT when D and Jk(a) antibodies may limit RBC supply and emphasizes the need for effective communication with the blood bank.

National trends in the prevalence of hepatitis B and C in South Korea, before and during the COVID-19 pandemic (2007-2021) - a nationwide representative study.

OBJECTIVE: Due to the various changes caused by the COVID-19 pandemic, some infectious diseases showed different epidemiology and prevalence during the pandemic. However, there is a lack of comprehensive studies on trends in the prevalence of hepatitis B and C related to the pandemic. Thus, we compared the prevalence of hepatitis B and C before and during the COVID-19 pandemic in South Korea. SUBJECTS AND METHODS: We conducted a comprehensive trend analysis with a nationwide serial cross-sectional survey from 2007 to 2021 (n=86,931) using the Korea National Health and Nutrition Examination Survey (KNHANES). The changes in the prevalence of hepatitis B and C were evaluated using a weighted regression model to assess the impact of the COVID-19 pandemic. RESULTS: From 2007 to 2021, 86,931 Korean adults aged 19 or older were included in the KNHANES data. The prevalence of hepatitis B showed a declining trend until the onset of the pandemic (1.80% in 2007-2009; 1.08% in 2016-2019; and 1.01% in 2020), at which point this trend reversed (1.39% in 2021). The prevalence of hepatitis C remained stable (0.14% in 2007-2009 and 0.18% in 2016-2019), with no particular surge related to the COVID-19 pandemic (ßdiff, -0.002; 95% CI, -0.761 to 0.756). For hepatitis B, old age was identified as a pandemic-related vulnerable factor (ratio of odds ratio, 1.68; 95% CI, 1.05-2.70). CONCLUSIONS: In this study, unlike other infectious diseases, hepatitis B and C did not show a decreasing trend during the pandemic. In particular, hepatitis B showed a rebound trend during the pandemic, which was noticeable in those aged 60 or older. Further studies are needed to support these findings.

Resection of the femoral neck: a new technique for the treatment of mallory type I intraoperative femoral fracture during total hip arthroplasty.

Intraoperative femoral fracture is a common complication during cementless total hip arthroplasty (THA). Cerclage wiring has been used for this type of fractures to attain intraoperative stability of the femoral stem. We designed a new technique to treat Mallory type 1 intraoperative femoral fractures. We excised fractured femoral neck fragment and without additional fixation and lightly tapped down the femoral stem to obtain a tight contact to the femoral cortex at the subtrochanteric level. In this case series, we described this technique and reported its outcomes. From January 2015 to December 2017, 600 cementless THAs (557 patients) were done with use of a proximally coated tapered stem design at our department. Among the 600 THAs, Mallory type 1 intraoperative femoral fracture occurred in 8 hips (8 patients), and all of them were treated with the excision of the fractured femoral neck. Mean age of the 8 patients was 58.1 years (range, 30.4 to 81.3 years) at the time of surgery. We report the results of this new technique at postoperative 2 to 5 years (mean, 3.4 years). All stems were placed in the neutral position. There was no revision and no stem showed any evidence of subsidence or loosening during the follow-up. The mean Harris hip score was 85.9 points at the latest follow-up. We recommend to use the femoral neck excision technique for the treatment of Mallory type 1 intraoperative femoral fractures.

High Estimated 24-Hour Urinary Sodium Excretion Is Related to Symptomatic Knee Osteoarthritis: A Nationwide Cross-Sectional Population-Based Study.

OBJECTIVES: High salt intake results in various harmful effects on human health including hypertension, cardiovascular disease, and reduced bone density. Despite this, there are very few studies in the literature that have investigated the association between sodium intake and osteoarthritis (OA). Therefore, we aimed to explore these associations in a Korean population. METHODS: This study used cross-sectional data from adult subjects aged 50-75 years from two consecutive periods of the Korean National Health and Nutrition Examination Survey V-VII (2010-2011 and 2014-2016). The estimated 24-hour urinary sodium excretion (24HUNa) was used as a surrogate marker of salt intake. In the 2010-2011 dataset, knee OA (KOA) was defined as the presence of the radiographic features of OA and knee pain. The association between KOA and salt intake was analysed using univariable and multivariable logistic regression methods. For the sensitivity analysis, the same procedures were conducted on subjects with self-reported OA (SR-OA) with knee pain in the 2010-2011 dataset and any site SR-OA in the 2014-2016 dataset. RESULTS: Subjects with KOA had significantly lower energy intake, but higher 24HUNa than those without KOA. The restricted cubic spline plots demonstrated a J-shaped distribution between 24HUNa and prevalent KOA. When 24HUNa was stratified into five groups (<2, 2-3, 3-4, 4-5 and ≥5 g/day), subjects with high sodium intake (≥5 g/day) had a higher risk of KOA (odds ratio [OR] = 1.64, 95% confidence interval [CI] 1.03-2.62) compared to the reference group (3-4 g/day) after adjusting for covariates. The sensitivity analysis based on SR-OA with knee pain showed that high sodium intake was also significantly associated with increased prevalence of OA (OR = 1.84, 95% CI 1.10-3.10) compared with the reference group. Regarding SR-OA at any site in the 2014-2016 dataset, estimated 24HUNa showed a significantly positive association with the presence of SR-OA after adjusting for potential confounders. CONCLUSIONS: This nationwide Korean representative study showed a significant association between symptomatic KOA and high sodium intake (≥5 g/day). Avoidance of a diet high in salt might be beneficial as a non-pharmacologic therapy for OA.

Incidence of subsequent osteoporotic fractures after distal radius fractures and mortality of the subsequent distal radius fractures: a retrospective analysis of claims data of the Korea National Health Insurance Service.

A better understanding of the features of subsequent fractures after distal radius fracture (DRF) is important for the prevention of further osteoporotic fractures. This study found that the cumulative incidence of subsequent osteoporotic fractures in South Korea increased over time and that the mortality rates of subsequent DRFs were lower than those of first-time DRFs. INTRODUCTION: We examined the incidence of osteoporotic fractures following distal radius fractures (DRFs) and the mortality rate after subsequent DRFs using claims data from the Korea National Health Insurance (KNHI) Service. METHODS: We identified records for 41,417 patients with first-time DRFs in 2012. The occurrence of osteoporotic fractures of the spine, hip, wrist, and humerus at least 6 months after the index DRF was tracked through 2016. All fractures were identified by specific diagnosis and procedure codes. One-year mortality rates and standardized mortality ratios (SMRs) for initial and subsequent DRFs were calculated for all patients. RESULTS: The 4-year cumulative incidence of all subsequent osteoporotic fractures was 14.74% (6105/41,417; 9.47% in men, 15.9% in women). The number of associated subsequent fractures was 2850 for the spine (46.68%), 2271 for the wrist (37.2%), 708 for the hip (11.6%), and 276 for the humerus (4.52%). The cumulative mortality rate 1 year after the first-time and subsequent DRF was 1.47% and 0.71%, respectively, and the overall SMR was 1.48 (95% CI: 1.37-1.61) and 0.71 (95% CI: 0.42-1.21), respectively. CONCLUSION: The cumulative incidence of osteoporotic fractures following DRFs increased over the study period and was higher among women. The cumulative mortality rates and SMRs of subsequent DRFs were lower than those of first-time DRFs at the 1-year follow-up. Given the increasing incidence rate of DRFs, the incidence of subsequent osteoporotic fractures may also increase.

Osteoporosis case ascertainment strategies in European and Asian countries: a comparative review.

While many clinical guidelines recommend screening for osteoporosis for early detection and treatment, there is great diversity in the case-finding strategies globally. We sought to compare case-finding strategies, focusing on the approaches used in European and Asian countries. This article provides an overview of the current case-finding strategies in the UK, Germany (including Austria and German-speaking regions of Switzerland), China, Japan, and Korea. We conducted a review of current treatment guidelines in each country and included expert opinions from key opinion leaders. Most countries define osteoporosis among patients with a radiographically identified fracture of the hip or the vertebrae. However, for other types of fractures, or in the absence of a fracture, varying combinations of risk-factor assessment and areal bone mineral density (aBMD) assessed by dual X-ray absorptiometry are used to define osteoporosis cases. A T-score ≤ - 2.5 is accepted to identify osteoporosis in the absence of a fracture; however, not all countries accept DXA alone as the sole criteria. Additionally, the critera for requiring clinical risk factors in addition to aBMD differ across countries. In most Asian countries, aBMD scanning is only provided beyond a particular age threshold. However, all guidelines recommend fracture risk assessment in younger ages if risk factors are present. Our review identified that strategies for case-finding differ regionally, particularly among patients without a fracture. More homogenized ways of identifying osteoporosis cases are needed, in both the Eastern and the Western countries, to improve osteoporosis case-finding before a fracture occurs.Case-finding in osteoporosis is essential to initiate treatment and minimize fracture risk. We identified differences in case-finding strategies between Eastern and Western countries. In the absence of a diagnosed fracture, varying combinations of risk factors and bone density measurements are used. Standardized case-finding strategies may help improve treatment rates.

Comparative risk of osteoporotic fracture among patients with rheumatoid arthritis receiving TNF inhibitors versus other biologics: a cohort study.

In this population-based cohort study on comparative osteoporotic fracture risks between different biologic disease-modifying drugs among patients with rheumatoid arthritis (RA), we did not find a significant difference in the risk of osteoporotic fractures between RA patients receiving TNF inhibitors versus abatacept or tocilizumab. INTRODUCTION: We aimed to investigate the comparative risk of osteoporotic fractures between rheumatoid arthritis (RA) patients who initiated TNF inhibitors (TNFis) versus abatacept or tocilizumab. METHODS: Using the Korea National Health Insurance Service datasets from 2002 to 2016, RA patients who initiated TNFis, abatacept, or tocilizumab were identified. The primary outcome was a composite end point of non-vertebral fractures and hospitalized vertebral fractures; secondary outcomes were two components of the primary outcome and fractures occurring at the humerus/forearm. Propensity score (PS) matching with a variable ratio up to 10 TNFi initiators per 1 comparator drug initiator was used to adjust for > 50 baseline confounders. We estimated hazard ratios (HRs) and 95% confidence interval (CI) of fractures comparing TNFi initiators to abatacept and to tocilizumab by Cox proportional hazard models stratified by a matching ratio. RESULTS: After PS-matching, 2307 TNFi initiators PS-matched on 588 abatacept initiators, and 2462 TNFi initiators on 640 tocilizumab initiators were included. A total of 77 fractures occurred during a mean follow-up of 454 days among TNFi and abatacept initiators and 83 fractures during 461 days among TNFi and tocilizumab initiators. The PS-matched HR (95% CI) was 0.91 (0.48-1.71) comparing TNFi versus abatacept initiators, and 1.00 (0.55-1.83) comparing TNFi versus tocilizumab initiators. Analysis on vertebral and non-vertebral fractures showed similar results. CONCLUSIONS: In this nationally representative cohort, we did not find a significant difference in the risk of fractures between TNFi initiators versus abatacept or tocilizumab among RA patients.

Second-generation Src/Abl inhibitor bosutinib effectively induces apoptosis in human esophageal squamous cell carcinoma (ESCC) cells via inhibiting Src/Abl signaling.

Esophageal cancer is a prevalent type of cancer worldwide and is ranked sixth among cancer-associated mortalities. Aberrant activation of the non-receptor tyrosine kinase Src and c-Abl contribute to the progression of ESCC. Thus, targeting these kinases to treat ESCC is a promising strategy. In this paper, we report that the potent dual Src/Abl inhibitor bosutinib exerts anti-tumor effects on ESCC. Bosutinib inhibits ESCC cell proliferation in a dose-dependent manner. Furthermore, bosutinib suppresses the colony formation ability of ESCC cells. Mechanistically, bosutinib effectively inhibits c-Abl and Src and its downstream signaling pathways, PI3K/AKT/mTOR and JAK/STAT3. In addition, bosutinib enhances the cytotoxic effects of doxorubicin on ESCC cells. In summary, our results reveal that Src and Abl are potential therapeutic targets in ESCC and that the novel Src/Abl inhibitor bosutinib alone or in combination with other chemotherapeutic agents may be a viable option for treating ESCC patients.

SARC-F as a Useful Tool for Screening Sarcopenia in Elderly Patients with Hip Fractures.

BACKGROUND: SARC-F is recommended as a sarcopenia screening tool and comprised of five assessment items: strength, assistance walking, rising from a chair, climbing stairs, and falls. OBJECTIVE: The purpose of this study was to assess whether the SARC-F questionnaire in elderly patients with hip fractures was a valid screening tool for sarcopenia by comparison of the results with criteria from the Europe, Asia, and international working groups. MEASUREMENTS: 115 men and woman with hip fractures were assessed. The SARC-F self-reported questionnaire scores range from 0 to 10 and a score ≥ 4 defines sarcopenia. These survey questions were used to calculate the SARC-F score. Measurements, including appendicular muscle mass, were taken using dual-energy X-ray and grip strength using a dynamometer. Classification using the SARC-F score was compared using the consensus panel criteria from the international, European, and Asian sarcopenia working groups. The performance of all four methods was compared by examining the predictive ability using a ROC curve. RESULTS: A total of 115 subjects were included and the sarcopenia prevalence rate (SARC-F score ≥ 4) was 63.5 percent. The sensitivity, specificity, positive predictive value, negative predictive value PPV with the EWGSOP-2 criteria in Older People as the reference standard were 95.35 %, 56.94 %, 56.94%, 95.35%, and 71.3%, respectively. In addition, we found similar results for sensitivity and specificity as studies using the EWGSOP and AWGS criteria. CONCLUSIONS: The SARC-F questionnaire is a useful screening tool for elderly patients with hip fractures. This finding supports the recommendation of SARC-F as a screening tool for sarcopenia from the EWGSOP2.

The change of bone mineral density and bone metabolism after gastrectomy for gastric cancer: a meta-analysis.

Bone mineral density (BMD) is significantly decreased after gastrectomy in patients with gastric cancer. Calcium malabsorption, secondary hyperparathyroidism, and dominant bone resorption appear to contribute to bone loss in these patients. Patients should undergo early surveillance and nutritional or pharmacologic intensive interventions for bone health. PURPOSE: Survivorship care, including bone health, has become an important issue in gastric cancer. We performed a meta-analysis of the available observational studies to determine whether and how osteoporosis risk is increased after gastrectomy in patients with gastric cancer. METHODS: A total of 1204 patients (802 men) from 19 cohort studies were included. We evaluated the prevalence of osteoporosis in postgastrectomy patients, comparing the incidence according to the type of gastrectomy and sex. Additionally, we evaluated changes in bone mineral density (BMD) and bone metabolism-related markers pre- to postoperatively and between patients who underwent gastrectomy and matched controls. Proportion meta-analysis was performed and pooled odds ratios (ORs) were calculated. RESULTS: The pooled incidence estimate was 36% [95% confidence interval (CI), 32-40]. The incidence of osteoporosis was significantly higher in women than in men (OR = 1.90, p < 0.001) but was similar between partial and total gastrectomy groups (OR = 0.983, p = 0.939). BMD was significantly decreased, and calcium, phosphorous, and parathyroid hormone levels were significantly increased in patients after gastrectomy compared to those before gastrectomy. BMD and calcium and 25OH-vitamin D levels were significantly decreased, and parathyroid hormone and 1,25OH-vitamin D levels were significantly increased in the gastrectomy group compared to that in the control group. CONCLUSION: We found that BMD is significantly decreased after gastrectomy in patients with gastric cancer. Vitamin D deficiency and secondary hyperparathyroidism are suggested to be common mechanism underlying BMD impairment. After resection, patients should undergo long-term nutritional and bone health surveillance, in addition to their oncological follow-up.

Development of microsatellite markers for the Japanese endemic conifer Thuja standishii and transfer to other East Asian species.

OBJECTIVE: Design polymorphic microsatellite loci that will be useful for studies of the genetic diversity, gene-flow and reproduction in the Japanese endemic conifer Thuja standishii and test the transferability of these loci to the two other East Asian species, T. sutchuenensis and T. koraiensis. RESULTS: Fifteen loci were developed which displayed 3 to 21 alleles per locus (average = 9.2) among 97 samples from three populations of T. standishii. Observed heterozygosity for all samples varied between 0.33 and 0.75 (average = 0.54) while expected heterozygosity values were higher with an average over the 15 loci of 0.62 (0.37-0.91). Low multi-locus probability of identity values (< 0.00002) indicate that these markers will be effective for identifying individuals derived from clonal reproduction. All 15 loci amplified in 13 samples of T. sutchuenensis, the sister species of T. standishii, with 1 to 11 alleles per locus (average = 4.33) while 13 loci amplified in four samples of the more distantly related T. koraiensis with 1 to 5 alleles per locus (average = 2.15).

Effect of improved medication adherence on health care costs in osteoporosis patients.

Osteoporosis is a chronic disease that requires continuous health care spending for pharmacotherapy and examinations. Osteoporotic fractures are a major economic burden. However, little is known about the economic effects of osteoporosis and osteoporotic fractures in Korea.The purpose of this study was to determine the predictors of osteoporosis-related health care costs and to evaluate the economic effects of fracture prevention through medication adherence among osteoporosis patients.Using the Korea National Health Insurance Claims Database (KNHICD), we identified osteoporosis patients aged 50 years and older from 2011 to 2012. Annual health care costs of osteoporosis were analyzed from the insurer's perspective and compared between patients with fractures and those without fractures. Adherents were defined as patients with a medication possession ratio of ≥80%. A generalized linear model (GLM) was used to estimate the predictors of osteoporosis-related health care costs.The major predictors of osteoporosis-related health care costs were age, medication adherence, and the occurrence of fractures (P < .001). The proportion of fractures among non-adherents was approximately 1.1 times the proportion among adherents. Health care costs per patient with fractures were 3.8 times the costs per patient without fractures. Patients with fractures had higher health care costs due to hospitalization and outpatient costs but lower pharmacy costs than non-adherents. We estimated that about $5 million of health insurance expenses could be saved annually if all non-adherents became adherents.Improved osteoporosis medication adherence can reduce osteoporosis-related health care costs by preventing fractures. Persistent pharmacotherapy for osteoporosis is necessary to prevent osteoporotic fractures and to reduce osteoporosis-related health care costs.

Parkinson's disease and the risk of osteoporotic vertebral compression fracture: a nationwide population-based study.

Patients with Parkinson's disease (PD) were at higher risk of osteoporotic vertebral compression fractures (OVCF) compared to controls and had elevated mortality rates. Compared to conservative treatment, surgical treatment for OVCF in PD patients seemed to be associated with better outcomes. INTRODUCTION: The purpose of this study was to evaluate the risk of OVCF in patients with PD. METHODS: Data from patients over the age of 60 years who were diagnosed with PD were collected between 2004 and 2013 from the Korean National Health Insurance Database (n = 3370). The comparison group (non-PD) consisted of randomly selected patients (five per patient with PD; n = 16,850) matched to the PD group, who were newly diagnosed annually according to age and sex. Cox proportional hazard regressions were used to examine the relationships between osteoporosis, OVCF, surgery for OVCF, and PD. Household income and residential area of patients were also assessed. Overall survival rates were calculated after adjusting for confounding factors, such as hypertension, diabetes mellitus, and chronic kidney disease. RESULTS: OVCF was developed in 12.5% of patients in the PD group and in 7.4% of patients in the control group. PD was associated with increased risk of osteoporosis (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.21-1.43; p < 0.001), OVCF (HR 1.66; 95% CI, 1.47-1.87; p < 0.001), and surgery for OVCF (HR 2.69; 95% CI, 1.78-4.08; p < 0.001). Household income was not significantly related with development of osteoporosis, incidence of OVCF, or surgery for OVCF. Residential area was statistically associated with osteoporosis, OVCF, and surgery for OVCF. The mortality rate of the PD group was about 1.7 times higher than that of the non-PD group after adjusting for potential confounders, and the mortality rate of the PD with OVCF group was higher than that of the non-PD group, but not significantly (p = 0.09). The survival rate of the PD group with surgery for OVCF showed a trend toward a more positive prognosis compared with that of the PD group with conservative treatment. CONCLUSIONS: Patients with PD had significantly increased risk of osteoporosis and OVCF. Surgical treatment for OVCF in PD patients was associated with a better prognosis than conservative treatment.

Validity of the intra-operative measurement of stem anteversion and factors for the erroneous estimation in cementless total hip arthroplasty using postero-lateral approach.

BACKGROUND: Intra-operative estimation of stem anteversion in total hip arthroplasty (THA) using postero-lateral approach is made by the surgeon's visual assessment, using the tibia as a guide, with the assumption that tibial axis is vertical to the trans-epicondylar axis. However, the accuracy of the intra-operative estimation has rarely been verified with postoperative CT-scans, with controversies regarding these measurements particularly in case of knee osteoarthritis. Therefore we performed a prospective study to: (1) determine the accuracy of the intra-operative measurement and (2) investigate factors affecting the discrepancy between the surgeon's estimation and the real stem anteversion. HYPOTHESIS: Intra-operative estimation of stem anteversion correlated with the real stem anteversion on CT-scan. PATIENTS AND METHODS: Sixty-seven THAs using cementless straight stems (65 patients) without ipsilateral total knee arthroplasty were prospectively evaluated to compare the intra-operative measurement of stem anteversion with the real stem anteversion on computed tomography (CT) scans. There were 33 men and 34 women with a mean age of 59.7years (range, 27-84years) at the time of surgery. Age, tibia plateau angle, native femoral anteversion, femoro-tibial angle, body mass index, operative site, gender, coronal and sagittal tilt of the stem, stem type, ipsilateral knee osteoarthritis, and preoperative diagnosis were analyzed to evaluate the factors affecting the discrepancy between the intra-operative and CT measurements. RESULTS: The intra-operative estimation (mean, 21.5°±8.5°; range, 5.0°-39.0°) was greater than the CT measurement (mean, 19.5°±8.7°; range, 4.5°-38.5°) by 2.0°. The mean absolute value of discrepancy was 4.5°. The correlation coefficient between intra-operative and CT measurements was 0.837. The femoro-tibial angle was associated with the discrepancy between the two measurements. In the presence of genu varum deformity, the intra-operative measurement underestimated the stem anteversion. DISCUSSION: Although intra-operative estimation of stem anteversion was slightly greater than the real stem anteversion, there was an excellent correlation between the two. The femoro-tibial angle should be considered to optimize the stem anteversion during cementless THA using postero-lateral approach. LEVEL OF EVIDENCE: Level III, prospective case control study.

Characterization of neural stem cells modified with hypoxia/neuron-specific VEGF expression system for spinal cord injury.

Spinal cord injury (SCI) is an incurable disease causing an ischemic environment and functional defect, thus a new therapeutic approach is needed for SCI treatment. Vascular endothelial growth factor (VEGF) is a potent therapeutic gene to treat SCI via angiogenesis and neuroprotection, and both tissue-specific gene expression and high gene delivery efficiency are important for successful gene therapy. Here we design the hypoxia/neuron dual-specific gene expression system (pEpo-NSE) and efficient gene delivery platform can be achieved by the combination ex vivo gene therapy with erythropoietin (Epo) enhancer, neuron-specific enolase (NSE) promoter and neural stem cells (NSCs). An in vitro model, NSCs transfected with pEpo-NSE were consistently and selectively overexpressing therapeutic genes in response to neural differentiation and hypoxic conditions. Also, in SCI model, ex vivo gene therapy using pEpo-NSE system with NSCs significantly enhanced gene delivery efficiency compared with pEpo-NSE system gene therapy alone. However, microarray analysis reveals that introducing exogenous pEpo-NSE and VEGF triggers biological pathways in NSCs such as glycolysis and signaling pathways such as Ras and mitogen-activated protein kinase, leading to cell proliferation, differentiation and apoptosis. Collectively, it indicates that the pEpo-NSE gene expression system works stably in NSCs and ex vivo gene therapy using pEpo-NSE system with NSCs improves gene expression efficiency. However, exogenously introduced pEpo-NSE system has an influence on gene expression profiles in NSCs. Therefore, when we consider ex vivo gene therapy for SCI, the effects of changes in gene expression profiles in NSCs on safety should be investigated.

RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain.

Although ubiquitin ligases have been implicated in autism, their roles and mechanisms in brain development remain incompletely understood. Here, we report that in vivo knockdown or conditional knockout of the autism-linked ubiquitin ligase RNF8 or associated ubiquitin-conjugating enzyme UBC13 in rodent cerebellar granule neurons robustly increases the number of parallel fiber presynaptic boutons and functional parallel fiber/Purkinje cell synapses. In contrast to the role of nuclear RNF8 in proliferating cells, RNF8 operates in the cytoplasm in neurons to suppress synapse differentiation in vivo. Proteomics analyses reveal that neuronal RNF8 interacts with the HECT domain protein HERC2 and scaffold protein NEURL4, and knockdown of HERC2 or NEURL4 phenocopies the inhibition of RNF8/UBC13 signaling on synapse differentiation. In behavior analyses, granule neuron-specific knockout of RNF8 or UBC13 impairs cerebellar-dependent learning. Our study defines RNF8 and UBC13 as components of a novel cytoplasmic ubiquitin-signaling network that suppresses synapse formation in the brain.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Mid-term results of the BIOLOX delta ceramic-on-ceramic total hip arthroplasty.

AIMS: We conducted a prospective study of a delta ceramic total hip arthroplasty (THA) to determine the rate of ceramic fracture, to characterise post-operative noise, and to evaluate the mid-term results and survivorship. PATIENTS AND METHODS: Between March 2009 and March 2011, 274 patients (310 hips) underwent cementless THA using a delta ceramic femoral head and liner. At each follow-up, clinical and radiological outcomes were recorded. A Kaplan-Meier analysis was undertaken to estimate survival. RESULTS: Four patients (four hips) died and 18 patients (20 hips) were lost to follow-up within five years. The remaining 252 patients (286 hips) were followed for a mean of 66.5 months (60 to 84). There were 144 men (166 hips) and 108 women (120 hips) with a mean age of 49.7 years (16 to 83) at surgery. The mean pre-operative Harris Hip Score of 47.1 points improved to 93.8 points at final follow-up. Six patients reported squeaking in seven hips; however, none were audible. Radiolucent lines involving Gruen zones one and/or seven were seen in 52 hips (18.2%). No hip had detectable wear, focal osteolysis or signs of loosening. One hip was revised because of fracture of the ceramic liner, which occurred due to an undetected malseating of the ceramic liner at the time of surgery. One hip was revised for a periprosthetic fracture of the femur, and one hip was treated for periprosthetic joint infection. The six-year survivorship with re-operation for any reason as the endpoint was 99.0% (95% confidence interval 97.8% to 100%). DISCUSSION: The rate of delta ceramic fracture was 0.3% (one of 286). While ceramic head fracture was dominant in previous ceramic-on-ceramic THA, fracture of the delta ceramic liner due to malseating is a concern. Cite this article: Bone Joint J 2017;99-B:741-8.

Atypical subtrochanteric fractures in Korean hip fracture study.

In Korean, atypical subtrochanteric fractures (ASF) were rare. Higher BMI and use of bisphosphonate were significant risk factors of ASF. INTRODUCTION: Recently, ASF have been reported to increase among patients on bisphosphonate. However, the incidence of ASF and the association between ASF and bisphosphonate use have not been well defined in Asian population. Our purposes are (1) to estimate the proportion of ASF among Korean patients with proximal femur fracture and (2) to determine the associated risk factors of ASF in the Korean patients. METHODS: We conducted a multicenter (16 academic hospitals), prospective Korean hip fracture study on hip fracture in a cohort of patients aged 50 years or older from South Korea between July 2014 and May 2016. As a part of Korean hip fracture study, primary analysis examined the proportion of ASF among proximal femur fracture. To identify ASF, according to the definition by ASBMR task force, all radiographs of subtrochanteric fracture were reviewed. Associated risk factors for occurrence of ASF were also evaluated by using multivariable logistic regression analysis. RESULTS: Among 1361 patients with proximal femoral fractures due to low-energy trauma, 17 fractures (1.2%) were identified as ASF. Higher BMI and use of bisphosphonate before injury were independent risk factors of ASF. CONCLUSION: In Korean, ASF were rare. Higher BMI and use of bisphosphonate were significant risk factors of ASF.

Total hip arthroplasty using a monobloc cementless femoral stem for patients with childhood Perthes' disease.

AIMS: Modular or custom-made femoral components have been preferred for total hip arthroplasty (THA) in patients with a history of Perthes' disease because of the distortion in the anatomy of the proximal femur. However, it has not been established whether a monobloc cementless stem will fit the distorted proximal femur or whether the results of the procedure are satisfactory in this group of patients. PATIENTS AND METHODS: We reviewed 68 consecutive patients who had undergone THA for childhood Perthes' disease between June 2003 and December 2008. There were 35 men and 33 women with a mean age of 48 years (16 to 73) at the time of index arthroplasty. Their mean body mass index was 24.4 (18.3 to 32.9). Of the 68 hips, 32 were classified as Stulberg class III and 36 as class IV. The mean pre-operative shortening of the affected leg was 17.2 mm (5 to 34). The minimum follow-up was five years (mean 8.5 years; 5.2 to 10). RESULTS: An intra-operative calcar fracture occurred in eight hips (11.8%) and was successfully treated by cerclage wiring. The mean stem version was 14.6° (-2.3 to 30; standard deviation (sd) 7.3). The mean acetabular component abduction was 40.2° (23.7 to 56.0; sd 6.5) and the mean anteversion 28.3° (6.4 to 43.0; sd 7.6), respectively. The mean follow-up was 8.5 years (5.2 to 10). No dislocations occurred and no hips were revised during the course of the study. At final follow-up, the mean Harris Hip Score was 91 points (59 to 100) and the mean University of California, Los Angeles activity score was 3.2 (2 to 8). CONCLUSION: Monobloc cementless stems reliably restore the anatomy in Perthes' disease at THA without the need for custom-made or modular implants. Cite this article: Bone Joint J 2017;99-B:440-444.