Presenilin deficiency enhances tau phosphorylation and its secretion.

Alzheimer's disease (AD) is characterized by the accumulation of abnormally folded amyloid ß-protein (Aß) in the brain parenchyma and phosphorylated tau in neurons. Presenilin (PS, PSEN) 1 and PS2 are essential components of γ-secretase, which is responsible for the cleavage of amyloid precursor protein (APP) to generate Aß. PSEN mutations are associated with tau aggregation in frontotemporal dementia, regardless of the presence or absence of Aß pathology. However, the mechanism by which PS regulates tau aggregation is still unknown. Here, we found that tau phosphorylation and secretion were significantly increased in PS double-knock-out (PS1/2-/-) fibroblasts compared with wild-type fibroblasts. Tau-positive vesicles in the cytoplasm were significantly increased in PS1/2-/- fibroblasts. Active GSK-3ß was increased in PS1/2-/- fibroblasts, and inhibiting GSK3ß activity in PS1/2-/- fibroblasts resulted in decreased tau phosphorylation and secretion. Transfection of WT human PS1 and PS2 reduced the secretion of phosphorylated tau and active GSK-3ß in PS1/2-/- fibroblasts. However, PS1D257A without γ-secretase activity did not decrease the secretion of phosphorylated tau. Furthermore, nicastrin deficiency also increased tau phosphorylation and secretion. These results suggest that deficient PS complex maturation may increase tau phosphorylation and secretion. Thus, our studies discover a new pathway by which PS regulates tau phosphorylation/secretion and pathology independent of Aß and suggest that PS serves as a potential therapeutic target for treating neurodegenerative diseases involving tau aggregation.

Experimental periprosthetic fractures with collarless polished tapered cemented stems.

PURPOSE: After cemented total hip arthroplasty, the risk of periprosthetic fracture (PPF) of taper-slip stems is higher than that of composite-beam stems. We aimed to assess the conditions resulting in PPFs of taper-slip stems using a falling weight. METHODS: Taper-slip stems were fixed to five types of simulated bone models using bone cement, and the fractures were evaluated by dropping stainless-steel weights from a predetermined height onto the heads. The periprosthetic fracture height in 50% of the bone models (PPFH50) was calculated using the staircase method. RESULTS: For the fixation with 0° of flexion, the values for PPFH50 were 61 ± 11, 60 ± 13, above 110, 108 ± 49, and 78 ± 12 cm for the cobalt-chromium-molybdenum alloy, stainless steel alloy (SUS), titanium alloy (Ti), smooth surface, and thick cement mantle models, respectively; for the fixation with 10° of flexion (considering flexure), the PPFH50 values were 77 ± 5, 85 ± 9, 90 ± 2, 89 ± 5, and 81 ± 11 cm, respectively. The fracture rates of the polished-surface stems were 78.6 and 35.7% at the proximal and distal sites, respectively (p < 0.05); the fracture rates of the smooth-surface stems were 14.2 and 100%, respectively (p < 0.05). CONCLUSION: The impact tests demonstrated that the conditions that were less likely to cause PPFs were use of Ti, a smooth surface, a thick cement mantle, and probably, use of SUS.

Validity of a preoperative scoring system for surgical management of periprosthetic hip infection: one-stage vs. two-stage revision.

INTRODUCTION: There are no widely accepted algorithms for determining optimal treatment for periprosthetic joint infection (PJI). Our study aimed to confirm the validity of a previously published scoring system in a larger number of patients to support a rational surgical treatment strategy for periprosthetic hip infection. MATERIALS AND METHODS: Between February 2001 and December 2020, we performed 155 consecutive revision total hip arthroplasties (THAs) for PJI, with mean follow-up of 6 years. One-stage revision THA was performed in 56 hips and two-stage revision THA in 99 hips. Prosthesis survival from recurrent infection was determined by Kaplan-Meier analysis, using implant removal as the endpoint. The pre-operative scoring system (full score of 12 points), including 6 essential elements, was retrospectively evaluated. RESULTS: The 10-year survival rates were 98% for one-stage (95% confidence interval [CI], 94-100) and 87% (95% CI, 79-96) for two-stage revision THA. Multivariate Cox regression analysis provided a total preoperative score as an independent risk factor for implant removal (hazard ratio, 0.17; 95% CI, 0.06-0.49; p < 0.001). The sensitivity and specificity at the cut-off of 4 points on the scoring system were 80% and 91%, respectively. The average score for one-stage revision THA in successful and failed cases were 8.9 and 6.0, and for two-stage revision THA were 6.5 and 3.9, respectively. We found significant differences between successful cases in one- and two-stage revision THA (p < 0.05). CONCLUSIONS: The preoperative scoring system was useful for managing PJI. One-stage revision THA is recommended in patients scoring ≥ 9 points, and meticulously performed two-stage revision THA is encouraged for patients scoring ≥ 4 points.

Presenilin Is Essential for ApoE Secretion, a Novel Role of Presenilin Involved in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a debilitating dementia characterized by progressive memory loss and aggregation of amyloid-ß (Aß) protein into amyloid plaques in patient brains. Mutations in presenilin (PS) lead to abnormal generation of Aß, which is the major cause of familial AD (FAD), and apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) onset. However, whether dysfunction of PS is involved in the pathogenesis of SAD is largely unknown. We found that ApoE secretion was completely abolished in PS-deficient cells and markedly decreased by inhibition of γ-secretase activity. Blockade of γ-secretase activity by a γ-secretase inhibitor, DAPT, decreased ApoE secretion, suggesting an important role of γ-secretase activity in ApoE secretion. Reduced ApoE secretion is also observed in nicastrin-deficient cells with reduced γ-secretase activity. PS deficiency enhanced nuclear translocation of ApoE and binding of ApoE to importin α4, a nuclear transport receptor. Moreover, the expression of PS mutants in PS-deficient cells suppressed the restoration effects on ApoE secretion compared with the expression of wild-type PS. Plasma ApoE levels were lower in FAD patients carrying PS1 mutations compared with normal control subjects. Our findings suggest a novel role of PS contributing to the pathogenesis of SAD by regulating ApoE secretion.SIGNIFICANCE STATEMENT Familial AD (FAD) typically results from mutations in the genes encoding amyloid precursor protein, presenilin 1 (PS1), or PS2. Many PS mutants have been found to exert impaired γ-secretase activity and increased amyloid-ß 42 (Aß42)/Aß40 ratio, which induce early amyloid deposition and FAD. On the other hand, apolipoprotein E4 (ApoE4) is the major genetic risk factor for sporadic AD (SAD) and contributes to AD pathogenesis because it has reduced Aß clearance capability compared with ApoE3 and ApoE2. FAD and SAD have long been considered to be caused by these two independent mechanisms; however, for the first time, we demonstrated that PS is essential for ApoE secretion and PS mutants affected ApoE secretion in vitro and in human samples, suggesting a novel mechanism by which PS is also involved in SAD pathogenesis.

Apolipoprotein E4 inhibits γ-secretase activity via binding to the γ-secretase complex.

The mechanisms of amyloid accumulation in familial Alzheimer's disease (FAD) and sporadic AD (SAD) are controversial. In FAD, mutations in presenilin (PSEN) impair γ-secretase activity and lead to abnormal amyloid ß-protein (Aß) production, thereby increasing the Aß42/40 ratio. SAD is postulated to be caused by decreased Aß clearance of apolipoprotein E4 (APOE4), the strongest risk factor for SAD. However, whether intracellular APOE4 affects Aß production is unclear. Using APOE3 and APOE4 knock-in (KI) mouse brain and primary cultured fibroblasts from these mice, in this study, we demonstrated that APOE3 and APOE4 bind to the γ-secretase complex and isoform-dependently regulate its activity and Aß production. We found that Aß40 levels and γ-secretase activity were higher in APOE knockout mouse brain than in wild-type mouse brain. APOE4-KI fibroblasts had significant lower Aß levels and γ-secretase activity but higher Aß42/40 ratio compared with APOE3-KI cells, indicating that APOE4-KI reduces Aß production by inhibiting γ-secretase activity. Interestingly, the levels of γ-secretase complex bound to APOE4 are higher than those bound to APOE3, and the levels of γ-secretase complex in the brain and fibroblasts of APOE4-KI mice were higher than those of APOE3-KI mice. Taken together, our findings demonstrate that intracellular APOE4 inhibits Aß production, more preferentially inhibits Aß40 production, and thereby induces an increase in the Aß42/40 ratio via binding to the γ-secretase complex. These results suggest a novel mechanism in which intracellular APOE4 contributes to the pathogenesis of SAD by inhibiting γ-secretase activity.

Ongoing vascular inflammation evaluated by 18F-fluorodeoxyglucose positron emission tomography in patients long after Kawasaki disease.

BACKGROUND: This study aimed to determine whether ongoing vascular inflammation presents in patients who had coronary artery aneurysms (CAAs) caused by Kawasaki disease (KD). METHODS: Subjects were 26 patients with a history of KD; 15 had giant CAA (gCAA) ≥ 8.0 mm and 11 had smaller CAA (smCAA) < 8 mm in the acute phase. They underwent X-ray computed tomography and 18F-fluorodeoxyglucose positron emission tomography. We determined the maximum coronary target-to-background ratio (CaTBR) and the mean thoracic aorta TBR (TaTBR) in each patient. They were compared between groups, and their correlation with various variables was determined. RESULTS: CaTBR and TaTBR were significantly higher in gCAA than in smCAA (P < .005 for both values) and were significantly higher even in patients without any metabolic risk factor (P < .05 for both values). The CAA size in acute phase significantly positively correlated with CaTBR (R2 = 0.32) as well as TaTBR (R2 = 0.28). Also, TaTBR significantly positively correlated with CaTBR (R2 = 0.32) as well as cumulative number of metabolic risk factors (trend, P = .03). CONCLUSIONS: Ongoing vascular inflammation may present long after KD, especially in patients with severe inflammation expressed as gCAA in the acute phase.

Treatment strategies for recurrent dislocation following total hip arthroplasty: relationship between cause of dislocation and type of revision surgery.

BACKGROUND: There are many therapeutic options for dislocation following total hip arthroplasty (THA). The aim of this study was to evaluate the results of revision surgery for dislocated hips. METHODS: Between November 2001 and December 2020, 71 consecutive revision hip surgeries were performed at our institution for recurrent dislocation following THA. We conducted a retrospective study of all 65 patients (71 hips), who were followed for a mean of 4.7 ± 3.2 years (range, 1-14). The cohort included 48 women and 17 men, with a mean age of 71 ± 12.3 years (range, 34-92). The mean number of previous surgeries was 1.6 ± 1.1 (range, 1-5). From intraoperative findings, we created six categories of revision hip surgery for recurrent dislocation following THA: open reduction and internal fixation (2 hips); head change or liner change only (6 hips); cup change with increased head size only (14 hips); stem change only (7 hips); cup and stem change (24 hips); and conversion to constrained cup (18 hips). Prosthesis survival was analyzed by the Kaplan-Meier method, with repeat revision surgery for re-dislocation or implant failure as the endpoint. A cox proportional hazards model was used for risk factors of re-revision surgery. RESULTS: Re-dislocation occurred in 5 hips (7.0%) and implant failure in 1 hip (1.4%). The 10-year survival rate was 81.1% (95% confidence interval, 65.5-96.8). A Dorr classification of "positional" was a risk factor for re-revision surgery due to re-dislocation. CONCLUSION: Clear understanding of the cause of dislocation is essential for optimizing revision procedures and improving the rate of successful outcomes.

Trochanteric Claw Plate Fixation for Greater Trochanteric Fracture or Osteotomy in Total Hip Arthroplasty.

This study retrospectively evaluated 41 consecutive open reductions and internal fixations following primary or revision total hip arthroplasty, which required trochanteric claw plate fixation for greater trochanteric fracture or osteotomy between January 2008 and December 2020. The mean duration of clinical follow-up was 4.2 years (range, 1-13 years). The patients included 13 men and 28 women, with a mean age of 68 years (range, 32-87 years). The indications for intervention included trochanteric osteotomy, intraoperative fracture, and non-union including postoperative fracture in 6, 9, and 26 cases, respectively. The mean Merle d'Aubigné Clinical Score improved from 9.4 points (range, 5-15 points) pre-operatively, to 14.3 points (range, 9-18 points) at the last follow-up. Bone union occurred in 35 cases (85%), while implant breakage occurred in four cases. At the last follow-up, the mean Merle d'Aubigné Clinical Scores of bone union and non-union were 15.3 and 14.1, respectively (p=0.48). The Kaplan-Meier survival rate, with the endpoint being revision surgery for pain, non-union, dislocation, or implant breakage, at 10 years was 80.0% (95% confidence interval: 62.6-97.4%). Greater trochanteric fixation using a trochanteric claw plate yielded successful results.

Can serum C-reactive protein determine the timing of reimplantation in two-stage revised arthroplasty for periprosthetic hip infection?

BACKGROUND: There are no definitive guides to determine the timing of reimplantation in two-stage revision total hip arthroplasties (THA) for periprosthetic joint infection (PJI). This study was to design to support a rational strategy of surgical treatment using serum C-reactive protein (CRP). METHODS: We analyzed a total of 75 hips for PJI in the process of performing two-stage and multiple-stage revision THAs. CRP level was retrospectively evaluated every week and transformed to log2 (CRP) using a logistic regression model. Prosthesis survival from recurrent infection was determined by Kaplan-Meier analysis, using implant removal as the endpoint. Receiver operating characteristic curves were calculated using each log2 (CRP) to assess predictions of recurrent infection. RESULTS: The 10-year survival rates were 85% (95% confidence interval, 76-95) and 100% for two-stage and multiple-stage revision THAs, respectively. Preoperatively, at 1, 2, 3, and 5 weeks, log2 (CRP) was not associated with recurrent infection. In failed two-stage revision THAs, log2 (CRP) at 3 weeks divided by that at 2 weeks showed a significant difference. Failure was associated with a ratio of >4.0 for the CRP level between 3 and 2 weeks. CONCLUSION: In two-stage revision THA for PJI, patients with CRP elevation from 2 weeks to 3 weeks, especially 4-fold elevation, suggests the need for further debridement and postponement of second-staged reimplantation.

High temperature promotes amyloid ß-protein production and γ-secretase complex formation via Hsp90.

Alzheimer's disease (AD) is characterized by neuronal loss and accumulation of ß-amyloid-protein (Aß) in the brain parenchyma. Sleep impairment is associated with AD and affects about 25-40% of patients in the mild-to-moderate stages of the disease. Sleep deprivation leads to increased Aß production; however, its mechanism remains largely unknown. We hypothesized that the increase in core body temperature induced by sleep deprivation may promote Aß production. Here, we report temperature-dependent regulation of Aß production. We found that an increase in temperature, from 37 °C to 39 °C, significantly increased Aß production in amyloid precursor protein-overexpressing cells. We also found that high temperature (39 °C) significantly increased the expression levels of heat shock protein 90 (Hsp90) and the C-terminal fragment of presenilin 1 (PS1-CTF) and promoted γ-secretase complex formation. Interestingly, Hsp90 was associated with the components of the premature γ-secretase complex, anterior pharynx-defective-1 (APH-1), and nicastrin (NCT) but was not associated with PS1-CTF or presenilin enhancer-2. Hsp90 knockdown abolished the increased level of Aß production and the increased formation of the γ-secretase complex at high temperature in culture. Furthermore, with in vivo experiments, we observed increases in the levels of Hsp90, PS1-CTF, NCT, and the γ-secretase complex in the cortex of mice housed at higher room temperature (30 °C) compared with those housed at standard room temperature (23 °C). Our results suggest that high temperature regulates Aß production by modulating γ-secretase complex formation through the binding of Hsp90 to NCT/APH-1.

Oral dysfunctions and cognitive impairment/dementia.

With global increases in the aging population, the number of patients with dementia is greatly increasing, which has become a big social problem. Many studies have shown strong associations between oral disorders and systemic disorders, such as diabetes, arthritis, sepsis, aspiration pneumonia, arteriosclerosis, bacterial endocarditis, and other cardiovascular diseases. Similarly, numerous cross-sectional studies showed that patients with dementia usually have poor oral conditions and tooth loss. These have long been considered as a result of difficulty with oral care due to impaired cognitive function, memory, and physical ability in patients with dementia. Indeed, even in patients with mild cognitive impairment, oral care becomes insufficient owing to decreases in spontaneity of grooming and finger dexterity. However, recent studies have shown that tooth loss and occlusal dysfunction may affect brain function and trigger the onset of dementia found in neurodegenerative diseases including Alzheimer's disease. In this review, we highlight the relationships among aging, oral dysfunction, and the development of dementia. Increasing evidence suggests that oral dysfunction is not only a result of dementia in the elderly people, but could also be a causative factor for the onset of dementia.

Two-hour postload plasma glucose and pigment epithelium-derived factor levels are markers of coronary artery inflammation in type 2 diabetic patients.

BACKGROUND: We have previously found that pioglitazone attenuates inflammation in the left main trunk of coronary artery (LMT), evaluated as target-to-background ratio (TBR) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with impaired glucose tolerance or type 2 diabetes. OBJECTIVES: We assessed which clinical variables could predict the change in TBR in the LMT after 4-month add-on therapy with oral hypoglycemic agents (OHAs). METHODS: A total of 38 type 2 diabetic patients with carotid atherosclerosis who had already received OHAs except for pioglitazone was enrolled. At baseline and 4 months after add-on therapy with pioglitazone or glimepiride, all patients underwent 75 g oral glucose tolerance test, blood chemistry analysis, and FDG-PET/CT. RESULTS: Fasting plasma glucose, 30-, 60-, 90-, 120-minutes postload plasma glucose, HbA1c, and LMT-TBR values were significantly decreased by add-on therapy, whereas high-density lipoprotein-cholesterol and adiponectin levels were increased. Increased serum levels of pigment epithelium-derived factor (PEDF), a marker of insulin resistance and non-use of aspirin at baseline could predict the favorable response of LMT-TBR to add-on therapy. Moreover, Δ120-minutes postload plasma glucose and ΔPEDF were independent correlates of ΔLMT-TBR. CONCLUSIONS: Our present study suggests that 120-minutes postload plasma glucose and PEDF values may be markers and potential therapeutic targets of coronary artery inflammation in type 2 diabetic patients. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov . Unique identifier: NCT00722631. New markers for diabetes and CAD is on the horizon! Two-hour postload plasma glucose and pigment epithelium derived factor are markers of coronary artery inflammation in type 2 diabetic patients.

Sonication of Extracted Implants Improves Microbial Detection in Patients With Orthopedic Implant-Associated Infections.

BACKGROUND: We assessed whether combining the conventional culture and implant sonicate fluid culture (SFC) methods increased the diagnostic accuracy of orthopedic implant-associated infection (OIAI). METHODS: Consecutive patients (n = 66) undergoing implant removal (OIAI, 17; non-OIAI, 49) were evaluated prospectively. We analyzed 493 samples (39 preoperative joint aspirates, 243 peri-implant tissue specimens, 124 implant sonication, 67 controls, and 20 water bath samples). OIAI was preoperatively evaluated based on clinical evidence of infection or aspirate culture (AC). Conventional methods required positive results in either preoperative ACs or intraoperative tissue cultures (TCs), whereas the combination method required at least 1 positive culture among 3 sources (AC, TC, or SFC). The application of SFC and the detection rate, sensitivity, and specificity of the diagnostic methods were assessed. RESULTS: No controls or water bath samples harbored bacteria. Three patients (18%) were detected by SFC only and Peptostreptococcus and Corynebacterium species were isolated by SFC only. The OIAI detection rate attributable to SFC was significantly higher than that of TC (61% vs 36%; P = .02). The sensitivities of AC, TC, and SFC at a cutoff point of 1 colony-forming unit/plate and 1 positive culture were 60%, 59%, and 71%, respectively. At a cutoff point of 2 positive cultures, the combination (vs conventional) method showed significantly greater sensitivity (71% vs 47%; P = .008). CONCLUSION: By incorporating SFCs into conventional culture methods, the diagnostic accuracy in the context of OIAI was significantly improved.

Reattachment of an osteotomized greater trochanter in total hip arthroplasty using an ultra-high molecular weight polyethylene fiber cable.

BACKGROUND: The optimum approach in total hip arthroplasty (THA) should reduce the risk of postoperative dislocation or limping, be applicable in every case, and be reusable in the future. The purpose of this study was to introduce our transgluteal approach for THA and to evaluate the type and frequency of complications around the greater trochanter. METHODS: This study retrospectively evaluated 892 THA cases between January 2010 and March 2015 performed using our transgluteal approach that osteotomized only the lateral anteroinferior greater trochanter. The trochanteric fragment was reattached using one of three different protocols: Group A, three non-absorbable polyester sutures; Group B, two non-absorbable polyester sutures and one ultra-high molecular weight polyethylene (UHMWPE) fiber cable; or Group C, two UHMWPE fiber cables. Postoperative complications were assessed and recorded, and univariate logistic regression analyses were performed to determine whether risk factors and radiological complications around the greater trochanter were correlated. RESULTS: None of the hips required revision for infection, dislocation, or limping. The rate of radiological complications around the greater trochanter at 1 year was 19.2% in Group A, 16.3% in Group B, and 7.9% in Group C (p < 0.001). Risk factors for radiological complications included the patient's disease or the surgeon's experience in Group A and the patient's age or the surgeon's experience in Group C. In the relationship between postoperative pain around the greater trochanter and radiological complications, there were no significant differences in all groups; no group interaction was observed (p= 0.3875). CONCLUSION: The UHMWPE fiber cable was effective to reduce complications of the reattached osteotomized greater trochanter in THA.

Vascular Inflammation Evaluated by [18F]-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Is Associated With Endothelial Dysfunction.

OBJECTIVE: Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. APPROACH AND RESULTS: We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8±9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (Δ%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between Δ%FMD and ΔTBR; ΔTBR was a sole independent associate of Δ%FMD in hypertensive patients (r=-0.558; P<0.001). CONCLUSIONS: The present study showed that vascular inflammation in the carotid arteries evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans.

Bone Remodeling in Acetabular Reconstruction Using a Kerboull-Type Reinforcement Device and Structural Bone-Grafting in Total Hip Arthroplasty.

BACKGROUND: The purpose of this study was to identify the long-term durability of the Kerboull-type reinforcement device (KT plate) in acetabular reconstruction for massive bone defects, assessing the remodeling of structural bone grafts. METHODS: This study retrospectively evaluated 106 hips that underwent acetabular reconstruction using a KT plate between November 2000 and December 2010. Thirty-eight primary total hip arthoplasties (THAs) and 68 revised THAs were performed, and the mean duration of clinical follow-up was 8 years (5-14 years). Regarding reconstructing the acetabular bone defects, autografts were used in 37 hips, allografts in 68 hips, and A-W glass ceramics in 2 hips. RESULTS: One hip exhibited radiological migration and no revision for aseptic loosening. The mean Merle d'Aubigné Clinical Score improved from 7.5 points (4-12 points) preoperatively to 10.9 points (9-18 points) at the last follow-up. The Kaplan-Meier survival rate for radiological migration of primary and revised THAs at 10 years was 100% and 97% (95% confidence interval: 96%-100%), respectively. Bone remodeling was evaluated using the radiological demarcation at the bone-to-bone interface, and an improvement of 100% in primary THAs and 94% in revised THAs was observed. CONCLUSION: For massive bone defects, acetabular reconstruction using the KT plate with a structural bone grafting can yield successful results.

In vivo serum concentration of vancomycin in antibiotic-loaded acrylic cement for the treatment and prevention of periprosthetic hip infection.

BACKGROUND: Although antibiotic-loaded acrylic cement (ALAC) is used to prevent and treat periprosthetic hip infection, it is unknown how much antibiotic is deposited in the body in vivo, how high the serum concentration rises, or how long its effects last. The aim of this study was firstly to determine the amount of vancomycin (VCM) deposited as ALAC in the body, and secondly to assess the safety and drug elution profile of VCM in ALAC. METHODS: We administered VCM to prevent infection after total hip arthroplasty (THA) or to treat patients with methicillin-resistant Staphylococcus aureus. Patients were classified into two groups: a low-dose group (21 hips) that received primary THA for high-risk cases, revision THA without infection, or one-staged revision THA for infection; and a high-dose group (6 hips) that received cement beads during a two-staged revision THA. The amount of VCM placed as ALAC into the hip was calculated using the remaining ALAC. The serum concentrations of VCM and creatinine were evaluated at postoperative days 1, 4, 7, 14, and 28, and at 3 and 6 months. RESULTS: The mean amount of VCM placed as ALAC into the hip was 0.9 g and 3.4 g for cemented THA and cement beads, respectively (P < 0.0001). The mean serum concentration of VCM from ALAC in the high-dose group was significantly increased compared with that in the low-dose group on postoperative days 1, 4, 7, 14, and 28 (P < 0.0001), but it remained within a clinically safe range. No significant differences were observed between the preoperative and postoperative serum creatinine levels of either group. CONCLUSION: The average serum concentrations of VCM from ALAC were always less than the effective blood concentration, and were detectable until 6 months after surgery.

Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects.

Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.