Multimodal Deep Learning-based Radiomics Approach for Predicting Surgical Outcomes in Patients with Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A retrospective analysis. OBJECTIVE: This research sought to develop a predictive model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using deep learning and machine learning (ML) techniques. SUMMARY OF BACKGROUND DATA: Determining surgical outcomes assists surgeons in communicating prognosis to patients and setting their expectations. Deep learning and ML are computational models that identify patterns from large datasets and make predictions. METHODS: Of the 482 patients, 288 patients were included in the analysis. A minimal clinically important difference (MCID) was defined as gain in Japanese Orthopaedic Association (JOA) score of 2.5 points or more. The predictive model for MCID achievement at 1 year post-surgery was constructed using patient background, clinical symptoms, and preoperative imaging features (x-ray, CT, MRI) analyzed via LightGBM and deep learning with RadImagenet. RESULTS: The median preoperative JOA score was 11.0 (IQR: 9.0-12.0), which significantly improved to 14.0 (IQR: 12.0-15.0) at 1 year after surgery (P < 0.001, Wilcoxon signed-rank test). The average improvement rate of the JOA score was 44.7%, and 60.1% of patients achieved the MCID. Our model exhibited an area under the receiver operating characteristic curve of 0.81 and the accuracy of 71.9% in predicting MCID at 1 year. Preoperative JOA score and certain preoperative imaging features were identified as the most significant factors in the predictive models. CONCLUSION: A predictive ML and deep learning model for surgical outcomes in OPLL patients is feasible, suggesting promising applications in spinal surgery. LEVEL OF EVIDENCE: 4.

A systematic review and meta-analysis of antibiotic-loaded bone cement for prevention of deep surgical site infections following primary total joint replacement.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) as a mean for preventing deep surgical site infections (SSI) after total joint replacement is controversial. Therefore, we have conducted a meta-analysis to evaluate the prophylactic effect of ALBC for SSI prevention in patients undergoing arthroplasty. This study was conducted to revise treatment guidelines for MRSA infections in Japan. METHODS: PubMed (Medline), Scopus, Embase, Web of Science and Cochrane library were searched for relevant articles comparing preventive effect of ALBC for patients undergoing primary total joint arthroplasty by August 2022. Primary outcome was the incidence of deep SSI. Subgroup analyses by type of surgery (total hip (THA) or knee (TKA) arthroplasty) and by causative pathogen (methicillin-resistant Staphylococcus aureus (MRSA)) were performed. RESULTS: Of the 3379 studies identified for screening, six studies involving 5745 patients were included. The use of ALBC significantly reduced the incidence of deep SSI in overall patients (risk ratio [RR] 0.60, 95% confidential interval [CI] 0.39-0.92), but the evidence level was very low. There was no significant preventive effect for ALBC compared with non-ALBC in both THA and TKA (THA, RR 0.52, 95% CI 0.23-1.16; TKA, RR 0.64, 95% CI 0.38-1.06), and for preventing MRSA-SSI (RR 0.27, 95% CI 0.03-2.41). CONCLUSIONS: Although the overall preventive effect of ALBC was significant, the evidence level was very low. Thus, the routine use of ALBC as a mean to prevent SSI in arthroplasty may not be suggested.

Muscle strength rather than appendicular skeletal muscle mass might affect spinal sagittal alignment, low back pain, and health-related quality of life.

Sarcopenia is defined as decreasing in muscle strength and mass, and dynapenia is defined as decreasing in muscle strength and maintained muscle mass. This study elucidated the prevalence and characteristics of sarcopenia and dynapenia and evaluate in elderly spinal disorders patients. 1039 spinal disorders patients aged ≥ 65 years were included. We measured age, grip strength, muscle mass, spinal sagittal alignment parameters, low back pain (LBP) scores and health-related quality of life (HR-QoL) scores. Based on the previous reports, patients were categorised into normal group: NG, pre-sarcopenia group: PG, dynapenia group: DG, and sarcopenia group: SG. Pre-sarcopenia, dynapenia, and sarcopenia were found in 101 (9.7%), 249 (19.2%), and 91 (8.8%) patients, respectively. The spinal sagittal alignment parameters, trunk muscle mass, LBP, and HR-QoL scores were significantly worse in DG and SG compared with those in PG and NG. Spinal alignment, trunk muscle mass, and clinical outcomes, including LBP and HR-QoL scores, were maintained in the PG and poor in the DG and SG. Thus, intervention for muscle strength may be a treatment option for changes of spinal sagittal alignment and low back pain.

Posterior Spinal Fusion Surgery for Neuromuscular Disease Patients with Severe Scoliosis Whose Cobb Angle Was over 100 Degrees.

Background and objectives: Patients with neuromuscular diseases usually have progressive neuromuscular scoliosis (NMS), requiring invasive surgery. Some patients present with severe scoliosis at the time of consultation and are difficult to treat. Posterior spinal fusion (PSF) surgery combined with anterior release and pre- or intraoperative traction would be effective for severe spinal deformities but would be invasive. This study aimed to evaluate the outcomes of PSF-only surgery for patients with severe NMS with a Cobb angle > 100°. Materials and Methods: Thirty NMS patients (13 boys and 17 girls; mean age 13.8 years) who underwent PSF-only surgery for scoliosis with a Cobb angle > 100° were included. We reviewed the lower instrumented vertebra (LIV), duration of surgery, blood loss, perioperative complications, preoperative clinical findings, and radiographic findings, including Cobb angle and pelvic obliquity (PO) in the sitting position pre- and postoperatively. The correction rate and correction loss of the Cobb angle and PO were also calculated. Results: The mean duration of surgery was 338 min, intraoperative blood loss was 1440 mL, preoperative %VC was 34.1%, FEV1.0 (%) was 91.5%, and EF was 66.1%. There were eight cases of perioperative complications. The Cobb angle and PO correction rates were 48.5% and 42.0%, respectively. We divided the patients into two groups: the L5 group, in which the LIV was L5, and the pelvis group, in which the LIV was the pelvis. The duration of surgery and PO correction rate in the pelvis group were significantly higher than those in the L5 group. Conclusions: Patients with severe NMS demonstrated severe preoperative restrictive ventilatory impairments. PSF surgery without anterior release or any intra-/preoperative traction showed satisfactory outcomes, including acceptable scoliosis correction and improved clinical findings, even in patients with extremely severe NMS. Instrumentation and fusion to the pelvis for severe scoliosis in patients with NMS showed good PO correction and low correction loss of Cobb angle and PO, but a longer duration of surgery.

Residual Neuropathic Pain in Postoperative Patients With Cervical Ossification of Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multi-institutional observational study. OBJECTIVE: To investigate and identify risk factors for residual neuropathic pain after surgery in patients with cervical ossification of posterior longitudinal ligament (c-OPLL). SUMMARY OF BACKGROUND DATA: Patients with c-OPLL often require surgery for numbness and paralysis of the extremities; however, postoperative neuropathic pain can considerably deteriorate their quality of life. METHODS: Out of 479 patients identified from multicenter c-OPLL registries between 2014 and 2017, 292 patients who could be followed up for 2 years postoperatively were reviewed, after excluding patients with nervous system comorbidities. Demographic details; medical history; radiographic factors including the K-line, spinal canal occupancy rate of OPLL, cervical kyphosis angle, and presence of spinal cord myelomalacia; preoperative Japanese Orthopaedic Association (JOA) score; surgical procedure (fusion or decompression surgery); postoperative neurological deterioration; and the visual analogue scale for pain and numbness in the upper extremities (U/E) or trunk/lower extremities (L/E) at baseline and at 2 years postoperatively were assessed. Patients were grouped into residual and non-residual groups based on a postoperative visual analogue scale ≥40 mm. Risk factors for residual neuropathic pain were evaluated by multiple logistic regression analysis. RESULTS: The prevalence of U/E and L/E residual pain in postoperative c-OPLL patients was 51.7% and 40.4%, respectively. The U/E residual group had a poor preoperative JOA score and longer illness duration, and fusion surgery was more common in the residual group than in non-residual group. The L/E residual group was older with a poorer preoperative JOA score. On multivariate analysis, risk factors for U/E residual pain were long illness duration and poor preoperative JOA score, whereas those for L/E residual pain were age and poor preoperative JOA score. CONCLUSIONS: The risk factors for residual spinal neuropathic pain after c-OPLL surgery were age, long duration of illness, and poor preoperative JOA score. LEVEL OF EVIDENCE: IV.

A High Body Mass Index and the Vacuum Phenomenon Upregulate Pain-Related Molecules in Human Degenerated Intervertebral Discs.

Animal studies suggest that pain-related-molecule upregulation in degenerated intervertebral discs (IVDs) potentially leads to low back pain (LBP). We hypothesized that IVD mechanical stress and axial loading contribute to discogenic LBP's pathomechanism. This study aimed to elucidate the relationships among the clinical findings, radiographical findings, and pain-related-molecule expression in human degenerated IVDs. We harvested degenerated-IVD samples from 35 patients during spinal interbody fusion surgery. Pain-related molecules including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, calcitonin gene-related peptide (CGRP), microsomal prostaglandin E synthase-1 (mPGES1), and nerve growth factor (NGF) were determined. We also recorded preoperative clinical findings including body mass index (BMI), Oswestry Disability Index (ODI), and radiographical findings including the vacuum phenomenon (VP) and spinal instability. Furthermore, we compared pain-related-molecule expression between the VP (-) and (+) groups. BMI was significantly correlated with the ODI, CGRP, and mPGES-1 levels. In the VP (+) group, mPGES-1 levels were significantly higher than in the VP (-) group. Additionally, CGRP and mPGES-1 were significantly correlated. Axial loading and mechanical stress correlated with CGRP and mPGES-1 expression and not with inflammatory cytokine or NGF expression. Therefore, axial loading and mechanical stress upregulate CGRP and mPGES-1 in human degenerated IVDs, potentially leading to chronic discogenic LBP.

Prevalence and location of endplate fracture and subsidence after oblique lumbar interbody fusion for adult spinal deformity.

BACKGROUND: Recently, Oblique lumbar interbody fusion (OLIF) is commonly indicated to correct the sagittal and coronal alignment in adult spinal deformity (ASD). Endplate fracture during surgery is a major complication of OLIF, but the detailed location of fracture in vertebral endplate in ASD has not yet been determined. We sought to determine the incidence and location of endplate fracture and subsidence of the OLIF cage in ASD surgery, and its association with fusion status and alignment. METHODS: We analyzed 75 levels in 27 patients were analyzed using multiplanar CT to detect the endplate fracture immediately after surgery and subsidence at 1 year postoperatively. The prevalence was compared between anterior and posterior, approach and non-approach sides, and concave and convex side. Their association with fusion status, local and global alignment, and complication was also investigated. RESULTS: Endplate fracture was observed in 64 levels (85.3%) in all 27 patients, and the incidence was significantly higher in the posterior area compared with the anterior area (85.3 vs. 68.0%, p=0.02) of affected vertebra in the sagittal plane. In the coronal plane, there was no significant difference in incidence between left (approach) and right (non-approach) sides (77.3 and 81.3%, respectively), or concave and convex sides (69.4 and 79.6%) of wedged vertebra. By contrast, cage subsidence at 1 year postoperatively was noted in 14/75 levels (18.7%), but was not associated with endplate fracture. Fusion status, local and global alignment, and complications were not associated with endplate fracture or subsidence. CONCLUSION: Endplate fracture during OLIF procedure in ASD cases is barely avoidable, possibly induced by the corrective maneuver with ideal rod counter and cantilever force, but is less associated with subsequent cage subsidence, fusion status, and sustainment of corrected alignment in long fusion surgery performed even for elderly patients.

Posterior Spinal Correction and Fusion Surgery in Patients with Spinal Muscular Atrophy-Associated Scoliosis for Whom Treatment with Nusinersen Was Planned.

INTRODUCTION: Spinal muscular atrophy (SMA) is defined as a neuromuscular disorder induced by progressive weakness of the skeletal muscle and is usually accompanied by progressive spinal deformity including scoliosis. The newly developed Nusinersen, which is the first approved drug worldwide for SMA, requires accurate intrathecal injection, which is sometimes difficult in patients with severe spinal deformity. TECHNICAL NOTE: For an accurate intrathecal approach in patients who have spinal fusion surgery to treat neuromuscular scoliosis, we have combined an L3 laminectomy with spinal correction and fusion surgery. Here, we review four cases of SMA in patients who underwent the additional L3 laminectomy during surgery to treat spinal scoliosis. A successful intrathecal approach was made using fluoroscopic guidance in all four patients, who were then administered with Nusinersen. CONCLUSIONS: Our findings show that additional lumbar laminectomy during surgery for spinal scoliosis has effectively allowed for intrathecal injection of Nusinersen.

Population Pharmacokinetic and Pharmacodynamic Target Attainment Analysis of Cefazolin in the Serum and Hip Joint Capsule of Patients Undergoing Total Hip Arthroplasty.

The objectives of this study were to evaluate the population pharmacokinetics of prophylactic cefazolin (CFZ) from its serum and hip joint capsule concentrations in patients undergoing total hip arthroplasty and to establish the pharmacodynamic target concentration exceeding the MIC for designing an effective dosing regimen for serum and the hip joint capsule. We analyzed 249 serum samples and 125 hip joint capsule samples from 125 individuals using a nonlinear mixed-effects model. The pharmacodynamic index target value obtained from our results indicates the probability of maintaining CFZ trough and hip joint capsule concentrations exceeding the MIC of 1 mg/liter to account for methicillin-susceptible S. aureus (MSSA). We estimated the population pharmacokinetics using a two-compartment model. The estimated population pharmacokinetic parameters were as follows: clearance (CL) (liters/h) = 1.46 × (creatinine clearance [CLcr] [ml/min]/77)0.891, volume of distribution of the central compartment (Vc) (liters) = 7.5, central-hip joint capsule compartment clearance (Q) (liters/h) = 3.38, and volume of distribution in the hip joint capsule compartment (VJC) (liters) = 36.1. The probability of achieving concentrations exceeding the MIC90 for MSSA was approximately 100% for serum and 100% for the hip joint capsule at 3 h after the initial dose. Our findings suggest that population-based parameters are useful for evaluating CFZ pharmacokinetics and that individual dosages should be determined based on the dosage regimen that achieves and maintains adequate tissue CFZ concentration.

Complete genome sequencing and comparative plasmid analysis of KPC-2-producing Klebsiella pneumoniae isolated from hospital sewage water in Japan.

OBJECTIVES: The Klebsiella pneumoniae carbapenemase (blaKPC) gene is one of the most widespread carbapenemase genes in the world. However, there are few reports on KPC-producing bacteria in Japan. The aim of this study was therefore to investigate KPC-producing K. pneumoniae in Japan. METHODS: A KPC-2-producingK. pneumoniae strain (KAM260) was isolated from hospital sewage water in Japan in 2018. The complete genome was determined by whole-genome sequencing. Subsequent comparative sequence analysis of the blaKPC-2-carrying plasmid was performed. RESULTS: Klebsiella pneumoniae KAM260, belonging to sequence type 3026 (ST3026), harboured the blaKPC-2 gene in 114.6-kbp plasmid pKAM260_2 with IncFIB(pQIL) and IncFII(K) replicons. pKAM260_2 was highly identical to pKpQIL-like plasmids, which carry blaKPC genes and have spread worldwide. pKAM260_2 had functional conjugation-associated genes and was transferable to Escherichia coli. CONCLUSION: pKAM260_2, the self-transmissible plasmid carrying theblaKPC-2 gene, was detected from hospital sewage water in Japan and was characterised as a pKpQIL-like plasmid. This plasmid needs to be monitored in Japan in the future owing to its high diffusivity.

Evaluation of myeloperoxidase in synovial fluid as a biomarker for chronic periprosthetic joint infection.

PURPOSE: There is no single biomarker that can perfectly diagnose periprosthetic joint infection (PJI). As diagnosing PJI remains a major challenge, accurate and rapid development of a biomarker is required. Myeloperoxidase (MPO) is a bactericidal enzyme that acts against pathogenic microorganisms, such as those found in PJI. We aimed to determine whether elevated MPO levels could be detected in infected synovial fluid and to evaluate its utility as a biomarker for diagnosing chronic PJI. METHODS: Patients who underwent revision total joint arthroplasty were categorised into two groups according to the criteria of the second International Consensus Meeting on Musculoskeletal Infection: chronic PJI or aseptic failure. MPO was measured in synovial fluid collected during surgery. Receiver operating characteristic curves were drawn, and the area under the curve, 95% confidence intervals, and sensitivity/specificity were calculated. RESULTS: Synovial fluid was obtained from 37 patients. Nineteen patients were categorised into the chronic PJI group and 18 in the aseptic failure group. MPO levels in the synovial fluid were significantly higher in the chronic PJI group than in the aseptic failure group (p < 0.001). This measurement demonstrated the diagnostic accuracy of MPO for diagnosing chronic PJI with high sensitivity and specificity. CONCLUSION: Although the results are debatable owing to the small sample size, measurement of MPO demonstrates high accuracy as a biomarker for diagnosing chronic PJI, and it may detect culture-negative chronic PJI. Furthermore, MPO can measure host response to chronic PJI without the potential of contamination.

Clinical usefulness of multiplex PCR-lateral flow for the diagnosis of orthopedic-related infections.

Objectives: Polymerase chain reaction (PCR)-based assays are being increasingly used for the diagnosis of orthopedic-related infections. Unfortunately, classical PCR requires imaging devices that are expensive and complex. We previously developed the PCR-lateral flow (PCR-LF) method, which does not require any additional imaging device. In the present study, the objective was to determine whether PCR-LF tests could be used to effectively diagnose orthopedic-related infections. Methods: In this study, we used PCR-LF to diagnose common causes of orthopedic-related infections and compared the results to those from conventional bacterial cultures of the same samples. Results: Notably, for 228 synovial fluid or pus specimens, the sensitivity and specificity of bacterial cultures were 53.5% and 97.7%, respectively, compared to 61.6% and 89.9% for PCR-LF. Although the difference in sensitivity between bacterial cultures and PCR-LF was not significant, when our analysis was limited to cases with suspected periprosthetic joint infection, the sensitivity of PCR-LF (66.1%) was superior to that of bacterial cultures (42.9%). Conclusion: This study indicates that PCR-LF is a useful method for diagnosing orthopedic-related infections.

Double-layered antibiotic-loaded cement spacer as a novel alternative for managing periprosthetic joint infection: an in vitro study.

BACKGROUND: Previous studies comparing antibiotic-loaded calcium phosphate cement to polymethylmethacrylate cement reported that although the former has higher elution volumes over a longer period, it is mechanically weak when used alone. To counter this problem, a double-layered antibiotic-loaded cement spacer in which calcium phosphate cement is coated with polymethylmethacrylate cement was created. METHODS: In this study, we compared the double-layered spacer to the polymethylmethacrylate cement spacer in terms of eluent antibiotic concentration, bioactivity against methicillin-resistant Staphylococcus aureus, and mechanical strength. Double-layered and polymethylmethacrylate cement spacers that were loaded with vancomycin (VCM) were prepared and immersed in phosphate buffer for 84 days. To facilitate VCM elution from calcium phosphate cores in double-layered spacers, we also drilled multiple holes into the calcium phosphate layer from the spacer surface. RESULTS: We found that VCM concentrations in double-layered spacer eluents were higher than those in polymethylmethacrylate cement spacer eluents. The double-layered spacer also had higher bioactivity than the polymethylmethacrylate cement spacer. Although the polymethylmethacrylate cement spacer eluent lost the ability to inhibit bacterial growth on day 56, the double-layered spacer eluent maintained this ability for the duration of our study. Finally, the double-layered spacer retained high mechanical strength throughout the study period. CONCLUSIONS: The beneficial biomechanical and drug-eluting properties of the double-layered spacer might qualify it to serve as a promising biomaterial that could be used for managing periprosthetic joint infections.

Time discounting, present biases, and health-related behaviors: Evidence from Japan.

Human health is considered the outcome of intertemporal choices under tradeoffs between a small immediate reward and a larger delayed reward. Health-related behaviors are thus affected by personal time preferences. Based on an Internet-based survey conducted on Japanese adults, we contribute to the literature by incorporating the multifaceted nature of time discounting in an analysis of the associations between time preference and health-related behaviors. We find that, first, less patient respondents tend to exhibit worse health-related attributes. Second, present bias, which is measured by the degree of declining impatience, is positively associated with unhealthy behaviors for naïve respondents, who are unaware of their self-control problem. Third, such associations cannot be found in sophisticates, who are aware of that. As a policy implication, direct intervention policies, including "nudging," are more effective than a commitment device provision in correcting the unhealthy behaviors due to present bias. Fourth, the sign effect, wherein future losses are discounted at a lower rate than future gains, is negatively associated with unhealthy outcomes, although at weak statistical significance levels.

Time discounting and smoking behavior: evidence from a panel survey(*).

By using a panel survey of Japanese adults, we show that smoking behavior is associated with personal time discounting and its biases, such as hyperbolic discounting and the sign effect, in the way that theory predicts: smoking depends positively on the discount rate and the degree of hyperbolic discounting and negatively on the presence of the sign effect. Positive effects of hyperbolic discounting on smoking are salient for naïve people, who are not aware of their self-control problem. By estimating smoking participation and smokers' cigarette consumption in Cragg's two-part model, we find that the two smoking decisions depend on different sets of time-discounting variables. Particularly, smoking participation is affected by being a naïve hyperbolic discounter, whereas the discount rate, the presence of the sign effect, and a hyperbolic discounting proxy constructed from procrastination behavior vis-à-vis doing homework assignments affect both types of decision making. The panel data enable us to analyze the over-time instability of elicited discount rates. The instability is shown to come from measurement errors, rather than preference shocks on time preference. Several evidences indicate that the detected associations between time preferences and smoking behavior are interpersonal one, rather than within-personal one.

Plaque distribution patterns in left main trunk bifurcations: prediction of branch vessel compromise by multidetector row computed topography after percutaneous coronary intervention.

AIMS: We investigated the mechanism and predictors of jailed branch vessel (BV) compromise during the stenting of left main trunk (LMT) bifurcation lesions from a multidetector row computed tomography (MDCT) analysis. METHODS AND RESULTS: Eighty patients who underwent MDCT and stenting for LMT bifurcation lesions were examined. The patients were retrospectively classified into a BV stenosis (BVS; n=38) group and a non-BV stenosis (NBVS; n=42) group according to a coronary angiography obtained just after crossover stent deployment for the target vessel (TV). The angle between the LMT and TV was significantly wider in the BVS group than in the NBVS group (140.2±10.3 degree vs. 132.6±14.2 degree, p=0.0076), and the frequency of carina side plaque at the TV in the long and short axis was significantly higher in the BVS group than in the NBVS group (50.0% vs. 16.7%; p=0.0012, 63.2% vs. 38.1%; p=0.0251, respectively). In a multivariate analysis, the presence of carina side plaque at the TV in the long and short axis were independent predictors of BVS (odds ratio: 5.15, p=0.0086, odds ratio: 3.83, p=0.0231, respectively). CONCLUSIONS: The plaque distribution and morphology assessed by MDCT may provide useful information that can predict the potential compromise of the BV during treatment for an LMT bifurcation lesion.

Late catch-up phenomenon associated with stent fracture after sirolimus-eluting stent implantation: incidence and outcome.

OBJECTIVE: To examine the long-term outcome of the stent fracture (SF) and the potential predictive factors contributing to in-stent restenosis (ISR) in the fractured stent. BACKGROUND: The SF is thought to be a higher risk of ISR in drug-eluting stent, although SF does not always develop ISR. METHODS: The consecutive 1,228 de novo lesions in 1,079 patients who underwent sirolimus-eluting stents implantation and assessed by 8 months follow-up coronary angiography were retrospectively analyzed. RESULTS: One hundred and seventeen SFs (9.5%) were identified in 100 patients and 22 (18.8%) SFs revealed ISR at the first follow-up. In addition, 16 (13.7%) developed new ISRs from 95 residual SFs without ISR prior to the second follow-up. Overall, 38 (32.5%) of all 117 SFs developed ISR, and 16 (42.1%) of 38 SFs occurred in a late phase beyond the first 8 months follow-up. A higher risk of ISR in the SF site was associated with the chronic total occlusion (ISR vs. no ISR: 34.2% vs. 16.5%, P = 0.0304), calcified lesions (55.3% vs. 34.2%, P = 0.0299), and correspondence 89.5% versus 43.0%, P < 0.0001 (SF site occurring at the original target lesion site) in the univariate analysis. The correspondence was identified as the only strong predictive factor for ISR at the SF site according to a multivariate logistic regression analysis (odds ratio 12.6, 95% confidence interval 3.82-53.5, P < 0.0001). CONCLUSIONS: SF occurring at the site of the original target lesion was a strong independent predictor of ISR. This indicates the need for a careful, long-term follow-up in those situations, even when no significant ISR is initially detected.

Identification of the active component that induces vancomycin resistance in MRSA.

A fraction of methicillin-resistant Staphylococcus aureus (MRSA) shows resistance to vancomycin (VCM) in the presence of ß-lactam antibiotics (BIVR) at low concentrations. We hypothesized that the BIVR phenomenon might be exerted by a peptidoglycan derivative(s) generated as a consequence of ß-lactam antibiotic action. To verify this hypothesis, we isolated the fraction that mimicked the effect of ß-lactam antibiotics by the enzymatic treatment of the crude cell wall. The active components were purified by a combination of reverse phase chromatographies, mass spectrum and amino-acid analyses, and were identified to be a muropeptide with the following formula: N-acetyglucosamyl-N-acetylmuramyl--Ala-D-isoGln-L-Lys-(ɛ-NH-4Gly)-D-Ala-2Gly. This is the very first identification of the active component, which induces VCM resistance in MRSA. We found that the BIVR cells are highly sensitive to this compound rendering the cells resistant to VCM compared with non-BIVR MRSA.