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The CaO-SiO2-P2O5-B2O3 glass-ceramic (BGS-7) spacer is a recently developed spacer that shows chemical bonding to bone with high mechanical stability. Further, this spacer achieves similar results to those of titanium cages. However, evidence regarding the advantages of the BGS-7 spacer is weak compared to polyetheretherketone (PEEK) cage. A randomized controlled trial is therefore warranted. The purpose of this study was to compare the radiographic and clinical efficacies and safety of the BGS-7 spacer compared to those of the PEEK cage in patients who underwent posterior lumbar interbody fusion (PLIF).The 54 participants who required one- or two-level PLIF due to lumbar degenerative disorders were randomly assigned to receive a BGS-7 spacer or PEEK cage. Visual analog scale (VAS), Oswestry Disability Index (ODI), European Quality of Life-5 Dimensions (EQ-5D), and painDETECT score were evaluated before surgery and at 3, 6, and 12 months after surgery. The fusion rate, degree of osteolysis, cage migration, and subsidence around the cage (spacer) were evaluated on computer tomography (CT) images at 12 months after surgery.The 12-month fusion rates were 77.8% in the BGS-7 spacer group and 81.0% in the PEEK cage group, with no significant difference (p = 0.807). The result regarding the non-inferiority of BGS-7 spacer was inconclusive. The linear mixed model showed no significant intervention effect in VAS, ODI, EQ-5D, and painDETECT score at the 3-, 6-, or 12-month follow-up. In addition, we found no significant between-group differences in the extent of osteolysis, spacer migration. However, the subsidence around the cage was significantly lower in the BGS-7 spacer group.This trial found similar fusion rates, and clinicoradiographic outcomes between the BGS-7 spacer and PEEK cage for PLIF. However, the non-inferiority was inconclusive. Safety concerns regarding fracture and migration of the BGS-7 spacer must be considered. Thus, the BGS-7 spacer design for PLIF surgery should be modified before further clinical use.

OBJECTIVE Changes in the thoracolumbar angle (TLA) would play a pivotal role in the reciprocal changes following spine realignment surgery, thereby leading to the development of proximal junctional kyphosis (PJK). This study aimed to investigate the association between TLA and the development of PJK following adult spinal deformity surgery. METHODS A total of 107 patients were divided into PJK+ and PJK− groups according to the development of PJK within 12 months after surgery. The TLA and spinopelvic radiological parameters were compared between the PJK+ and PJK− groups. A multivariate logistic regression model was used to identify the risk factors for PJK. The receiver operating characteristic curves of the regression models were used to investigate the cutoff values of significant parameters needed so that PJK would not occur. RESULTS The change in TLA (ΔTLA) in the PJK+ group was significantly larger than in the PJK− group (6.7° ± 7.9° and 2.2° ± 8.1°, respectively; p = 0.006). Multivariate logistic regression analysis demonstrated that age, postoperative pelvic incidence–lumbar lordosis, and ΔTLA were significant risk factors for PJK. The risk of developing PJK was higher when the postoperative pelvic incidence–lumbar lordosis was < 5.2 and the ΔTLA was > 3.58°. CONCLUSIONS The present study highlights the thinking that extensive correction of TLA and lumbar lordosis should be avoided in patients with adult spinal deformity. Overcorrection of TLA of > 3.58° could result in higher odds of PJK.

Trials guidance: The Abstract should not exceed 350 words. Please minimize the use of abbreviations and do not cite references in the abstract. The abstract must include the following separate sections: • Background: No studies have compared the clinical outcome and radiographic outcome between window and non-window three-dimensional titanium (3D-Ti) cages. Therefore, well designed a randomized controlled trial (RCT) is needed. This multicenter, prospective RCT will compare the outcomes of window and non-window 3D-Ti cage in lumbar interbody fusion surgery. • Methods: Study participants will be randomly assigned to the active intervention group or control intervention group in a 1:1 ratio and undergone a one-level posterior lumbar interbody fusion (PLIF) for degenerative lumbar disease. The window type 3D-Ti cage will be used in the participants assigned to the control intervention group. And the non-window type 3D-Ti cage will be used in the participants assigned to the active intervention. The clinical and radiographic outcomes between two groups will be compared serially until postoperative 12-months. • Discussion: This trial designated for evaluating the equivalence of the clinical outcome between window and non-window 3D-Ti cage and will provide data on the effectiveness and safety of non-window type 3D-Ti cage. • Trial registration: Clinical Research Information Service (cris.nih.go.kr) (KCT 0005793). Registered on 19 January 2021

This study aimed to validate the usefulness of the global alignment proportion (GAP) score to predict postoperative mechanical failure in the elderly (mean age, 70.5 years) individuals with severe sagittal imbalance. A total of 84 patients were enrolled: mechanical complications (MC), minor mechanical complications (mMC), proximal junctional failure (PJF), and revision surgery occurred in 61% (51/84), 58% (49/84), 44% (37/84), and 13% (11/84) of the patients, respectively. The GAP score was calculated using the X-ray obtained in the early postoperative period. The validity of the GAP score’s predictive ability was evaluated by calculating the area under the curve (AUC) of the receiver operating characteristics curve. Univariate logistic regression analysis and Cochran–Armitage test of trend were performed to determine the association between mechanical complications and GAP score. The discriminatory power of GAP score to predict MC, mMC, and PJF was “moderately accurate,” with an AUC of 0.839 (confidence interval [CI] 0.755–0.824, p

Study Design Retrospective review. Objectives To establish a cutoff value for hand grip strength and predict the favorable outcomes of adult spinal deformity surgery. Summary of Background Data Hand grip strength (HGS) has been suggested to predict surgical outcomes in various fields, including adult spinal deformity (ASD). However, to the best of our knowledge, no study has established a cutoff value for HGS in patients with ASD. Methods This study included 115 female patients who underwent reconstructive spinal surgery for ASD between September 2016 and September 2020. HGS was measured preoperatively. The Oswestry Disability Index (ODI), EuroQOL-5-dimension (EQ-5D), and visual analog scale (VAS) scores for back pain were all recorded both before and after surgery. Patients were dichotomized either into favorable or unfavorable outcome groups using an ODI cutoff score of 22 at 1 year after surgery. Multivariate logistic regression analysis was done to identify significant factors leading to favorable outcomes. A receiver operating characteristic (ROC) curve was drawn to define the cutoff value of HGS for favorable outcomes. Results Multivariate logistic regression analysis showed that HGS is significantly associated with favorable surgical outcomes in ASD ( P = .031). The ROC curve suggested a cutoff value of 14.20 kg for HGS (area under the curve (AUC) = .678, P = .013) to predict favorable surgical outcomes in ASD. The surgical complications were not significantly affected by HGS. Conclusion The HGS of patients with ASD can be interpreted with a cutoff value of 14.20 kg. Patients with HGS above this cutoff value showed superior surgical outcomes at 1 year after surgery compared to those below this cutoff value.

Over the past few decades, interest in minimally invasive spine surgery (MISS) has increased tremendously due to its core principle of minimizing approach-related injury while providing outcomes similar to traditional open spine procedures. With technical and technological advancements, MISS has expanded its utility not only to simple spinal stenosis, but also to complex spinal pathologies such as metastasis, trauma, or adult spinal deformity. In this article, we review the techniques and technology in MISS and discuss the indications, benefits, and limitations of MISS.

Study design: Prospective randomized controlled trial.Background: The CaO-SiO2-P2O5-B2O3 glass-ceramic (BGS-7) spacer is a recently developed spacer that shows chemical bonding to bone with high mechanical stability. Further, this spacer achieves similar results to those of titanium cages. However, evidence regarding the advantages of the BGS-7 spacer is weak compared to polyetheretherketone (PEEK) cage. A randomized controlled trial is therefore warranted. The purpose of this study was to compare the radiographic and clinical efficacies and safety of the BGS-7 spacer compared to those of the PEEK cage in patients who underwent posterior lumbar interbody fusion (PLIF). Methods: The 54 participants who required one- or two-level PLIF due to lumbar degenerative disorders were randomly assigned to receive a BGS-7 spacer or PEEK cage. Visual analog scale (VAS), Oswestry Disability Index (ODI), European Quality of Life-5 Dimensions (EQ-5D), painDETECT score were evaluated before surgery and at 3, 6, and 12 months after surgery. The fusion rate, degree of osteolysis, cage migration and subsidence around the cage (spacer) were evaluated on computer tomography (CT) images at 12 months after surgery. Results: The 12-month fusion rates were 75% in the BGS-7 spacer group and 79.3% in the PEEK cage group, with no significant difference (p=0.676). The result regarding the non-inferiority of BGS-7 spacer was inconclusive. The linear mixed model showed no significant intervention effect in VAS, ODI, EQ-5D, and painDETECT score at the 3-, 6-, or 12-month follow-up. In addition, we found no significant between-group differences in the extent of osteolysis, spacer migration. However, the subsidence around the cage was significantly lower in the BGS-7 spacer group. Conclusions: This trial found similar fusion rates, clinicoradiographic outcomes, and adverse events between the BGS-7 spacer and PEEK cage for PLIF. However, the non-inferiority was inconclusive, and thus, the BGS-7 spacer can be a feasible and safe alternative to PEEK cage in PLIF surgery after further studies.

This study aimed to investigate how preoperative motion analysis results affect the postoperative clinical outcomes of patients undergoing surgery for adult spinal deformity (ASD).Patients who underwent surgery for ASD and whose motion analysis results were available were included. All patients underwent preoperative three-dimensional gait analysis using a motion analysis system. Univariate and multivariate regression analyses were performed to determine the predictive parameters of the 12-month postoperative Oswestry Disability Index (ODI). According to the mean anterior pelvic tilt (Ant-PT) angle in the motion analysis, the patients were divided into two groups: small and high Ant-PT angle groups. The 12-month postoperative ODI between the two groups was compared.A total of 111 patients who met the inclusion criteria were enrolled in the study. In the multivariate regression analysis, the preoperative sacral slope and mean Ant-PT angle were significant predictors of the 12-month postoperative ODI (p = 0.013 and p = 0.009, respectively). The high Ant-PT angle group showed a poorer 12-month postoperative ODI than did the small Ant-PT angle group, with a mean ODI of 21.9 ± 8.4 and 16.7 ± 8.5, respectively (p = 0.002). Simple linear regression analysis revealed that the Ant-PT angle was positively correlated with the postoperative sagittal vertical axis in all follow-up periods.The study highlights that a high preoperative Ant-PT angle in motion analyses is associated with poor clinical outcomes after surgery for ASD. Therefore, it is necessary to observe and consider the dynamic gait pattern related to the compensatory mechanism for sagittal imbalance in the decision-making process for ASD surgery.

This study aimed to examine which motion analysis parameters regarding the dynamic aspects and/or balance affect the development acute proximal junctional kyphosis (PJK) following adult spinal deformity (ASD) surgery. A total of 90 consecutive patients were recruited prospectively, who underwent a corrective surgery for ASD with sagittal imbalance. According to the development of acute PJK within 6 months after surgery, the patients were divided into the PJK+ and PJK− groups. Before surgery, three-dimensional gait analyses were performed using a motion analysis system. The preoperative continuous and categorical variables were compared between the PJK+ and PJK− groups using independent t tests and chi-square tests, respectively. Finally, a multivariate logistic regression model was used to identify the risk factors and calculate the odds ratio (OR) for acute PJK. A total of 20 and 70 patients were classified into the PJK+ and PJK− groups, respectively. There were no differences in the spinopelvic radiologic parameters pre- and postoperatively between the PJK+ and PJK− groups. The PJK+ group showed a significantly higher mean anterior pelvic tilt (Ant-PT) angle in preoperative motion analysis than the PJK− group (P = 0.001 for both sides). Multivariate analysis identified the mean Ant-PT angle (P = 0.047; OR 1.127; 95% CI 1.002–1.267) as a significant risk factor for acute PJK. Preoperative Ant-PT angle during walking was associated with a higher OR in acute PJK after surgery.

This study aimed to validate the usefulness of the global alignment proportion (GAP) score to predict postoperative mechanical failure in the elderly (mean age, 70.5 years) individuals with severe sagittal imbalance.A total of 84 patients were enrolled: mechanical complications (MC), minor mechanical complications (mMC), proximal junctional failure (PJF), and revision surgery occurred in 61% (51/84), 58% (49/84), 44% (37/84), and 13% (11/84) of the patients, respectively. The GAP score was calculated using the X-ray obtained in the early postoperative period. The validity of the GAP score's predictive ability was evaluated by calculating the area under the curve (AUC) of the receiver operating characteristics curve. Univariate logistic regression analysis and Cochran-Armitage test of trend were performed to determine the association between mechanical complications and GAP score.The discriminatory power of GAP score to predict MC, mMC, and PJF was "moderately accurate," with an AUC of 0.839 (confidence interval [CI] 0.755-0.824, p 0.001), 0.836 (CI 0.749-0.923, p 0.001), and 0.702 (CI 0.588-0.851, p 0.001), respectively. The GAP score showed a statistically significant association with MC, mMC, and PJF in univariate logistic regression analysis and Cochran-Armitage test for trend. However, it was not significantly associated with revision surgery.This study showed promising results regarding the GAP score's predictive power for MC, mMC, and PJF in the elderly population with degenerative kyphoscoliosis. Using the GAP score, we can determine the patient's specific correction goal preoperatively to prevent mechanical failure based on individual patient's characteristics such as pelvic incidence.

Health risks from galactic cosmic rays (GCR) in space travel above low earth orbit remain a concern. For many years accelerator experiments investigating space radiation induced prevalence of murine Harderian gland (HG) tumorigenesis have been performed to help estimate GCR risks. Most studies used acute, relatively low fluence, exposures. Results on a broad spectrum of individual ions and linear energy transfers (LETs) have become available. However, in space, the crew are exposed simultaneously to many different GCR. Recent upgrades at the Brookhaven NASA Space Radiation Laboratory (NSRL) now allow mixtures in the form of different one-ion beams delivered in rapid sequence. This paper uses the results of three two-ion mixture experiments to illustrate conceptual, mathematical, computational, and statistical aspects of synergy analyses and also acts as an interim report on the mixture experiments' results. The results were interpreted using the following: (a) accumulated data from HG one-ion accelerator experiments; (b) incremental effect additivity synergy theory rather than simple effect additivity synergy theory; (c) parsimonious models for one-ion dose-effect relations; and (d), computer-implemented numerical methods encapsulated in freely available open source customized software. The main conclusions are the following. As yet, the murine HG tumorigenesis experimental studies show synergy in only one case out of three. Moreover, some theoretical arguments suggest GCR-simulating mixed beams are not likely to be synergistic. However, more studies relevant to possible synergy are needed by various groups that are studying various endpoints. Especially important is the possibility of synergy among high-LET radiations, since individual high-LET ions have large relative biological effectiveness for many endpoints. Selected terminology, symbols, and abbreviations. DER - dose-effect relation; E(d) - DER of a one-ion beam, where d is dose; HG prevalence p - in this paper, p is the number of mice with at least one Harderian gland tumor divided by the number of mice that are at risk of developing Harderian gland tumors (so that in this paper prevalence p can never, conceptually speaking, be greater than 1); IEA - incremental effect additivity synergy theory; synergy level - a specification, exemplified in Fig.5, of how clear-cut an observed synergy is; mixmix principle - a consistency condition on a synergy theory which insures that the synergy theory treats mixtures of agent mixtures in a mathematically self-consistent way; NTE - non-targeted effect(s); NSNA - neither synergy nor antagonism; SEA - simple effect additivity synergy theory; TE - targeted effect(s); β* - ion speed relative to the speed of light, with 0 < β* < 1; SLI - swift light ion(s).

Background Vertebral fragility fracture (VFF) is a common fracture related to osteoporosis. However, VFF might be asymptomatic and often occurs in patients without osteoporosis. Therefore, we investigated the characteristics of age-related VFF and their correlation with bone mineral density (BMD). Furthermore, we analyzed other factors affecting VFF Methods Medical records from a single center were retrospectively reviewed for 2,216 patients over 50 years old with vertebral fractures conservatively treated from 2005 to 2016. Patients' age, gender, body mass index (BMI), BMD, fracture level, previous vertebral fractures, and anti-osteoporosis medications were obtained. Patients were divided into fragility/non-fragility groups and age sub-groups. The odds ratio for VFF in relation to BMD was evaluated. We also identified other predictive factors for VFF by age groups. Results The fragility group had a higher women ratio, older age, lower BMI, lower BMD, and greater incidence of previous vertebral fractures than the non-fragility group. VFFs were seen in 41.18% of normal BMD patients aged 50–59 and 67.82% of those aged 60–69. The proportion of VFFs increased with age in all WHO osteoporosis classifications. Patients with osteopenia and osteoporosis were 1.57 and 2.62 fold more likely to develop VFFs than normal BMD. In the younger group (under 70), age, women, BMD, and previous vertebral fracture were significant factors affecting VFF, and in the older group (70 and over), age, women, and BMD were factors. In the fragility group, anti-osteoporosis medication rates were 25.08% before and 45.96% after fracture. Conclusion Considerable VFFs occurred in the younger age groups without osteoporosis and age itself was another important predictor of VFF especially in older age groups. The discrepancy between the incidence of VFF and BMD suggests the necessity of supplemental screening factors and anti-osteoporosis treatment guidelines using only BMD should be reconsidered., Graphical Abstract

To evaluate the diagnostic value of stress radiography and determine the cutoff values for high-grade anterolateral rotatory laxity in complete anterior cruciate ligament (ACL)-deficient knees at different positions. Forty-two patients with complete ACL rupture (group 1) and 37 normal subjects (group 2) were prospectively enrolled. The amount of anterior translation in the medial (MM) and lateral (LL) distance compartments and the difference between them (LL-MM distance) were measured using stress radiography at 30°, 45°, 60°, and 90° positions. The area under the receiver operating characteristic curve (AUC) was assessed for the presence of a high-grade (grade > 2) pivot shift. The MM and LL distances in group 1 were significantly different at 30° and 45° positions (P

To evaluate the incidence and risk factors of postoperative hyperextension after mobile-bearing total knee arthroplasty (TKA) and its clinical outcomes. This retrospective case–control study included 387 knees of primary TKA patients after a 5-year follow-up. The clinical outcomes and radiographs including posterior condylar offset (PCO), femur and tibial slope angle and its discrepancy were evaluated. The patients were divided into two groups (group 1: non-hyperextension, group 2: hyperextension). An extension greater than 5° measured using a goniometer at the final follow-up was defined as hyperextension. Logistic and linear regression analyses were performed. Overall, 43 knees (11.1%) with hyperextension were observed at the last follow-up. There was no significant difference between groups in terms of the clinical outcomes although the functional scores were worse in group 2. There was no significant difference in the postoperative radiologic evaluation except for a change in PCO (group 1 vs. group 2; − 0.2 mm ± 3.8 vs. − 2.4 mm ± 3.0, p = 0.003), distal femoral resection slope angle (− 9.1° ± 2.1 vs. − 12.1° ± 1.7, p

Twenty-eight rats were randomized into two groups: a control group comprising a collagen sheet with only cast BMP-2; and an experimental group comprising a collagen sheet with BMP-2 photo-immobilized using azidophenyl gelatin. Micro-computed tomography analysis revealed that there was more regenerated bone in experimental group at both 4 and 8 weeks. Immunohistochemical analysis revealed that the positively expressed cellular ratio in RUNX2-stained cells were significantly higher in experimental group. These results demonstrate that BMP-2 photo-immobilized using Az-Gel on a collagen sheet shows promising bone regeneration, and the sheet is a good candidate of BMP-2 carrier.

The osteogenetic potential of photo-immobilized azdiophenyl (Az)-natural polymers as a carrier of bone morphogenetic protein-2 (BMP-2) was assessed in 56 rats randomized to four groups. The control group comprised implanted collagen sheet with BMP-2. In the three experimental groups, the implant comprised collagen sheet with photo-immobilized BMP-2 on Az-gelatin (Az-Gel), Az- O -carboxymethyl chitosan (Az-OMC), or Az‑ O ‑carboxymethyl low molecular chitosan (Az-LMC). Micro-computed tomography analysis revealed more regenerated bone in Az-Gel at 8 weeks. Immunohistochemical analysis at 4 weeks revealed that the positively expressed cellular ratio in RUNX2-stained cells was significantly higher in Az-Gel and Az-OMC groups. At 8 weeks, only the Az-Gel group showed higher positively expressed cellular ratio compared with the control group. These results demonstrate the superior osteogenetic potential of photo-immobilized BMP-2 using Az-Gel carrier in a rat calvarial defect model compared with control group. Photo-immobilization of BMP-2 using Az-gelatin could be a more effective carrier system of BMP-2 than a chitosan-based carrier system.

To investigate whether cartilage thickness in the lateral femoral posterior condyle affects the femoral rotation angles on navigation and clinical outcomes of navigation-assisted total knee arthroplasty (TKA). This is a prospective randomized study of navigation-assisted TKA. Fifty cases underwent TKA without removal of the lateral posterior femoral cartilage (Group 1), and 56 cases underwent TKA with removal of the lateral posterior femoral cartilage (Group 2). The femoral rotation was evaluated using CT and compared with navigation values. The angle between the clinical transepicondylar axis and posterior condylar axis measured on CT was defined as the femoral rotation angle on CT. Elevation of the joint line and patellar measurements were also evaluated. The clinical outcomes were not statistically different in the two groups. The radiographic measurements were not statistically different except femoral rotation angle on navigation. The mean femoral rotation angle of navigation was 4.0° ± 2.2° without cartilage removal and 5.1° ± 2.5° with cartilage removal. The reliability and validity were high between the femoral rotation angle on navigation in the cartilage removal group and that on CT, but there were no differences in clinical outcomes between the two groups. There was little effect of navigation-assisted TKA on radiographic and clinical outcomes, although femoral rotational differences were caused by the lateral femoral posterior condylar cartilage. Although the rotational differences due to cartilage would be within the clinical safety margin, surgeons should consider that difference during TKA. Lower quality randomized trial (no masking), Level II.

Systematic literature review. To review the evidence from high-quality studies regarding the treatment of neuropathic pain originating specifically from spinal disorders. In general, treatment guidelines for neuropathic pain cover all its various causes, including medical disease, peripheral neuropathy, and cancer. However, the natural history of neuropathic pain originating from spinal disorders may differ from that of the pain originating from other causes or lesions. An expert research librarian used terms related to neuropathic pain and spinal disorders, disc herniation, stenosis, and spinal cord injury to search in MEDLINE, Embase, and Cochrane CENTRAL for primary research from January 2000 to October 2015. Among 2,313 potential studies of interest, 25 randomized controlled trials (RCTs) and 21 systematic reviews (SRs) were included in the analysis. The selection was decided based on the agreement of two orthopedic surgeons. There was a lack of evidence about medication for radiculopathy arising from disc herniation and stenosis, but intervention procedures, including epidural block, showed positive efficacy in radiculopathy and also limited efficacy in spinal stenosis. There was some evidence based on the short-term follow-up regarding surgery being superior to conservative treatments for radiculopathy and stenosis. There was limited evidence regarding the efficacy of pharmacological and electric or magnetic stimulation therapies for neuropathic pain after spinal cord injury. This review of RCTs and SRs with high-quality evidence found some evidence regarding the efficacy of various treatment modalities for neuropathic pain related specifically to spinal disorders. However, there is a need for much more supportive evidence.

Background Recently, biplanar fluoroscopy is used to evaluate the cervical kinematics, especially to locate the instant center of rotation (ICR) during in vivo motion. This study aims to ascertain the ICR at each cervical segment in the sagittal plane during dynamic motion and assess the differences from previous studies. Methods While three healthy subjects were performing full flexion-extension, two oblique views aligned horizontally and angled at approximately 55° were obtained by biplanar fluoroscopy. The minimum degree to detect significant movement in a helical axis model was set at 2°, and anterior-posterior and superior-inferior locations of each ICR were defined. To evaluate the possible distribution area and overlapping area of the ICR with disc space, we drew a circle by using the calculated distance between each coordination and the mean coordination of ICR as the radius. Results During flexion-extension motion, the mean superior-inferior location of the ICR became progressively more superior, except the C5-6 segment (p = 0.015), and the mean anterior-posterior location of the ICR became progressively more anterior without exception from C2-3 to C6-7 segments, but anterior-posterior ICR locations were not significantly different among segments. The overlapping area with the distribution circle of ICR was mainly located in the posterior half in the C3-4 segment, but the overlapping area was about 80% of the total disc space in C4-5 and C6-7 segments. The overlapping was more noticeable in the lower cervical segments after exclusion of the outlier data of the C5-6 segment in subject 1. Conclusions The ICR in the cervical spine showed a trend of moving progressively more superiorly and anteriorly and the disc space overlapping the distribution circle of ICR increased along the lower motion segments except the C5-6 segment. These findings could provide a good basis for level-specific cervical arthroplasty designs.

Customized open-source software is used to characterize, exemplify, compare and critically evaluate mathematical/computational synergy analysis methods currently used in biology, and used or potentially applicable in radiobiology. As examples, we reanalyze some published results on murine Harderian gland tumors and on in vitro chromosome aberrations induced by exposure to single-ion radiations that simulate components of the galactic cosmic ray field. Baseline no-synergy/no-antagonism-mixture dose-effect relationships are calculated for corresponding mixed fields. No new experimental results are presented. Synergy analysis of effects due to a mixed radiation field whose components' individual dose-effect relationships are highly curvilinear should not consist of simply comparing to the sum of the components' effects. Such curvilinearity must often be allowed for in current radiobiology, especially when studying possible non-targeted ("bystander") effects. Consequently, many different synergy analysis theories are currently used in biology to replace simple effect additivity. We give evidence that for most synergy experiments and observations, incremental effect additivity is the most appropriate replacement. It has a large domain of applicability, being useful even when pronounced individual dose-effect relationship curvilinearity is a confounding factor. It allows calculation of 95% confidence intervals for baseline mixture dose-effect relationships taking into account parameter correlations; if non-targeted effects are important this gives much tighter intervals than neglecting the correlations. It always obeys two consistency conditions that simple effect additivity usually fails to obey: a "mixture of mixtures principle" and the standard "sham mixture principle". The mixture of mixtures principle is important in radiobiology because even nominally single-ion radiations are usually mixtures when they strike the biological target, due to intervening material. It is not yet clear whether mixing galactic cosmic ray components sometimes leads to statistically significant synergy for animal tumorigenesis. The substantial limitations of synergy theories are sometimes overlooked, and they warrant further study.

Ceramic-on-ceramic articulation has the lowest wear with little osteolysis. However, the wear and osteolysis in long-term follow-up are not known. Another concern is ceramic fracture, which might occur after repeated stress during a long period. Ninety hips (76 patients with a mean age of 47 years) that underwent cementless total hip arthroplasty using third-generation ceramic-on-ceramic articulation were followed for 14-16 years. At final follow-up, there was no measurable ceramic wear and no periprosthetic osteolysis was identified. No ceramic fracture occurred during the follow-up. One hip was revised because of late infection. All prostheses were bone-ingrown. Two patients experienced a grinding sensation. However, no patient had squeak. The mean Harris hip score at the final evaluation was 89 points and the survival rate was 98.9%.