Increased infiltration of CCR4-positive regulatory T cells in prostate cancer tissue is associated with a poor prognosis.

BACKGROUND: Regulatory T cells (Tregs) play important roles in the suppression of immune responses, including antitumor immune responses. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. This study aimed to evaluate the expression of CCR4-positive Tregs (CCR4+Tregs) in prostate cancer and estimate the clinical potential of CCR4-targeting therapy for prostate cancer. METHODS: A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. The relationships between the number of CCR4+Tregs and clinical parameters were investigated in RP and biopsy specimens. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration-resistant prostate cancer (CRPC) within 12 months (n = 13) and those with good prognosis who were stable with hormone-sensitive prostate cancer over 12 months (n = 47). Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them. RESULTS: There was a higher expression of CCR4+Tregs in RP specimens with a higher (≥8) Gleason score than in those with a lower (<8) Gleason score (P = .041). In biopsy specimens, 65.9% Tregs were positive for CCR4. The number of CCR4+Tregs positively correlated with clinical stage (P < .001) and Gleason score (P = .006). The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group compared with that in the good prognosis group (P = .024 and .01, respectively). Furthermore, patients with lower CCR4+Treg expression levels showed a significantly longer time to progression to CRPC (not reached vs 27.3 months; P < .001) and median survival time (not reached vs 69.0 months; P = .014) than those with higher expression levels. CONCLUSIONS: CCR4+Tregs are highly infiltrated in the prostate tissue of patients with poor prognosis with potential to progress to CRPC. Furthermore, the degree of infiltration of CCR4+Tregs is related to the prognosis of prostate cancer.

Targeting lactate dehydrogenase­A promotes docetaxel­induced cytotoxicity predominantly in castration­resistant prostate cancer cells.

Docetaxel (DOC) is one of the most effective chemotherapeutic agents against castration­resistant prostate cancer (CRPC). Despite an impressive initial clinical response, the majority of patients eventually develop resistance to DOC. In tumor metabolism, where tumors preferentially utilize anaerobic metabolism, lactate dehydrogenase (LDH) serves an important role. LDH controls the conversion of pyruvate to lactate, with LDH­A, one of the predominant isoforms of LDH, controlling this metabolic process. In the present study, the role of LDH­A in drug resistance of human prostate cancer (PC) was examined by analyzing 4 PC cell lines, including castration­providing strains PC3, DU145, LNCaP and LN­CSS (which is a hormone refractory cell line established from LNCaP). Sodium oxamate (SO) was used as a specific LDH­A inhibitor. Changes in the expression level of LDH­A were analyzed by western blotting. Cell growth and survival were evaluated with a WST­1 assay. Cell cycle progression and apoptotic inducibility were evaluated by flow cytometry using propidium iodide and Annexin V staining. LDH expression was strongly associated with DOC sensitivity in PC cells. SO inhibited growth of PC cells, which was considered to be caused by the inhibition of LDH­A expression. Synergistic cytotoxicity was observed by combining DOC and SO in LN­CSS cells, but not in LNCaP cells. This combination treatment induced additive cytotoxic effects in PC­3 and DU145 cells, caused cell cycle arrest in G2­M phase and increased the number of cells in the sub­G1 phase of cell cycle in LN­CSS cells. SO promoted DOC induced apoptosis in LN­CSS cells, which was partially caused by the inhibition of DOC­induced increase in LDH­A expression. The results strongly indicated that LDH­A serves an important role in DOC resistance in advanced PC cells and inhibition of LDH­A expression promotes susceptibility to DOC, particularly in CRPC cells. The present study may provide valuable information for developing targeted therapies for CRPC in the future.

Intra-articular administration of EP2 enhances the articular cartilage repair in a rabbit model.

We have reported the usefulness of chondrocyte sheets on articular cartilage repair in animal experiments. Here, we investigated the regenerative effects of EP2 signalling with or without chondrocyte sheets. Forty-five rabbits were used, with six rabbits in each of the six groups and nine rabbits for chondrocytes and synovial cells harvesting to fabricate triple-layered chondrocyte sheets: osteochondral defect only (control, Group A), EP2 agonist (Group B), EP2 antagonist (Group C), chondrocyte sheets (Group D), EP2 agonist and chondrocyte sheets (Group E), and EP2 antagonist and chondrocyte sheets (Group F). After surgery, the weight distribution ratio was measured as an indicator of pain alleviation. Injections of the EP2 agonist or EP2 antagonist were given from 4 weeks after surgery. The rabbits were sacrificed at 12 weeks, and the repaired tissues were evaluated for histology. The weight distribution ratio and International Cartilage Repair Society grading were as follows: Group A: 40.5% ± 0.2%, 14.8 ± 0.5; Group B: 43.4% ± 0.7%, 25.4 ± 0.8; Group C: 38.7% ± 0.7%, 13.7 ± 0.3; Group D: 48.6% ± 0.6%, 40.2 ± 0.5; Group E: 49.1% ± 0.3%, 40.5 ± 0.4; and Group F; 46.8% ± 0.4%, 38.7 ± 0.5. Significant differences in histology and pain alleviation were observed between groups except between Groups A and C, between Groups D and E, and between Groups D and F. These findings show that the intra-articular administration of an EP2 agonist achieved pain alleviation and tissue repair. However, no synergistic effect with chondrocyte sheets was observed.

Optimal Measurement Level and Ulnar Nerve Cross-Sectional Area Cutoff Threshold for Identifying Ulnar Neuropathy at the Elbow by MRI and Ultrasonography.

PURPOSE: Imaging criteria for diagnosing compressive ulnar neuropathy at the elbow (UNE) have recently been established as the maximum ulnar nerve cross-sectional area (UNCSA) upon magnetic resonance imaging (MRI) and/or ultrasonography (US). However, the levels of maximum UNCSA and diagnostic cutoff values have not yet been established. We therefore analyzed UNCSA by MRI and US in patients with UNE and in controls. METHODS: We measured UNCSA at 7 levels in 30 patients with UNE and 28 controls by MRI and at 15 levels in 12 patients with UNE and 24 controls by US. We compared UNCSA as determined by MRI or US and determined optimal diagnostic cutoff values based on receiver operating characteristic curve analysis. RESULTS: The UNCSA was significantly larger in the UNE group than in controls at 3, 2, 1, and 0 cm proximal and 1, 2, and 3 cm distal to the medial epicondyle for both modalities. The UNCSA was maximal at 1 cm proximal to the medial epicondyle for MRI (16.1 ± 3.5 mm2) as well as for US (17 ± 7 mm2). A cutoff value of 11.0 mm2 for MRI and US was found to be optimal for differentiating between patients with UNE and controls, with an area under the receiver operating characteristic curve of 0.95 for MRI and 0.96 for US. The UNCSA measured by MRI was not significantly different from that by US. Intra-rater and interrater reliabilities for UNCSA were all greater than 0.77. The UNCSA in the severe nerve dysfunction group of 18 patients was significantly larger than that in the mild nerve dysfunction group of 12 patients. CONCLUSIONS: By measuring UNCSA with MRI or US at 1 cm proximal to the ME, patients with and without UNE could be discriminated at a cutoff threshold of 11.0 mm2 with high sensitivity, specificity, and reliability. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

Custom-made, antibiotic-loaded, acrylic cement spacers using a dental silicone template for treatment of infected hip prostheses.

PURPOSE: Antibiotic-loaded acrylic cement (ALAC) spacers are useful for treatment of infected prostheses in the course of a two-stage revision. Spacers are handmade or are made using a commercial template, with reportedly good treatment outcomes. This study aimed to confirm the usefulness of custom-made ALAC spacers shaped like bipolar hip prostheses using a dental silicone template for treatment of infected hip prostheses, and described their manufacture. METHODS: This study evaluated 10 patients who underwent two-stage revision for treatment of infected hip prostheses. Custom-made ALAC spacers were used in all patients. Templates were made with dental silicone. We investigated the following in treatment of the infected hip prostheses: bacterial pathogens; antibiotic-cement mixtures; waiting time to revision; dislocation, breakage, and migration of custom-made ALAC spacers; current hip status; progress during follow-up; presence or absence of recurrence; and walking ability. RESULTS: Dislocation, breakage, and migration were not observed in custom-made ALAC spacers. All patients recovered after two-stage revision without additional surgery and showed no recurrence during the follow-up period. CONCLUSION: Custom-made ALAC spacers shaped like bipolar hip prostheses using a template made of dental silicone may be useful for treatment of infected hip prostheses.

Treatment status and radiographic features of patients with atypical femoral fractures.

BACKGROUND: The Japanese Orthopaedic Association (JOA) has been surveying approximately 3000 orthopedic surgery hospitals and clinics with inpatient facilities nationwide to collect information on atypical femoral fractures (AFFs) and patient characteristics since 2010. The present study aims to examine radiographic images and clarify the relationship between radiographic and patient characteristics of patients with AFF and treatment status. METHODS: The study involved 1996 facilities certified as clinical training sites by the JOA and 912 clinics with inpatient facilities affiliated with the Japanese Clinical Orthopaedic Association (JCOA). Additional clinical data collection and radiographic image review were performed in patients aged 35 years or older who met the American Society for Bone and Mineral Research (ASBMR) case definition for AFF and received treatment at participating facilities registered with JOA in 2013. Radiographic images were evaluated in accordance with the ASBMR case definition. RESULTS: Radiographic images of 304 fractures in 304 patients were collected. Among them, 230 fractures were determined to be AFFs. The fracture site was the proximal third in 70 AFFs (30.4%), middle third in 157 AFFs (68.3%), and distal third in 3 AFFs (1.3%). Among patients with AFFs, 173 (75.2%) were treated with bisphosphonates (BPs) and 45 patients (19.6%) were not (unknown in 12 patients). Duration of use was three years or longer in 103 patients (59.5%) and between one and three years in 24 patients (13.9%). Radiographic beaking was observed in 149 fractures (86.1%) in patients treated with BPs and 17 fractures (37.8%) in patients who were not treated with BPs (odds ratio 11.3, 95% CI 5.7-22.3). CONCLUSIONS: Radiographic beaking was observed more frequently in patients treated with BPs than in patients not treated with BPs.

Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis.

The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (Cmax)/MIC = 8. Prostatic penetration of pazufloxacin was good with mean Cmax ratios (prostate tissue/plasma) of 0.82-0.99 and for AUC, 0.80-0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L.

Fibroma of Tendon Sheath Presenting Limited Flexion of the Fingers.

A 35-year-old Japanese man presented with a 1-month history of limited flexion and radiating pain in the left middle and ring fingers. A physical examination revealed a hard nodular mass in his left palm. Magnetic resonance imaging showed a 2 × 1.5 × 1 cm mass of low intensity on T1-weighted images and high intensity on T2-weighted images and gadolinium enhancement. The tumor was marginally resected, adhering to the flexor digitorum profundus of both the third and fourth fingers. The histological diagnosis was fibroma of tendon sheath. After the surgery, the range of motion and hand function were improved. No recurrence has been observed. Fibroma of tendon sheath usually arises on the fingers and hands with strong attachment to the tendon or tendon sheath. The tumor in the present case probably limited the range of flexion of the fingers by obstruction of the transverse carpal ligament.

Blood metal ion concentrations in metal-on-metal total hip arthroplasty.

INTRODUCTION: The hip placement with a metal-on-metal (MOM) bearing has been used for both surface replacement and total hip arthroplasty (THA). Use of MOM bearing for hip replacement reduces the wear compared to conventional bearings. METHODS: We prospectively assessed 30 patients who underwent unilateral MOM THA. A control group of 30 patients who underwent metal-on-polyethylene THA using the implants as the other group, except for bearing, were accessed. Blood samples were collected preoperatively and at 3- , 6- , 9- , 12- , 15- , 18- , and 24-month intervals. Changes in mean blood metal ion concentration were compared between the MOM and metal-on-polyethylene groups. RESULTS: A statistically significant positive correlation was observed between blood cobalt and chromium concentrations in all of the patients. The mean blood ion concentrations of the MOM were significantly higher than those of the metal-on-polyethylene. A statistically significant negative correlation was found between maximum blood cobalt concentration and cup version angle. The maximum blood chromium concentrations in the patients who had larger cup version angles were more likely to decrease. CONCLUSIONS: We considered that cup version angle is one of the factors that have the greatest effect on blood metal ion concentration, and the target cup version angle that did not induce an increase in blood metal ion concentrations was approximately 20°.

Usefulness of measuring acetabular anterior coverage using a tomosynthesis imaging system.

PURPOSE: The purpose of this study was to compare the usefulness of measuring acetabular anterior coverage by tomosynthesis and false profile (FP) radiography. METHODS: 70 hips in 35 patients who were diagnosed with early stage osteoarthritis of the hip, and 60 hips from 30 healthy volunteers were analysed. Plain FP radiographs were taken, and vertical-centre-anterior margin (FP-VCA) angles were measured. Acetabular anterior coverage was measured in the natural standing position using a tomosynthesis imaging system in the sagittal plane. As with FP radiography, we measured vertical-centre-anterior margin (TS-VCA) angles. RESULTS: The median values of the FP-VCA angle, and TS-VCA angle were 43.8°, 54.4°, respectively. The TS-VCA angle was significantly larger than the FP-VCA angle. For FP radiographs, the intraobserver intraclass correlation coefficient (ICC) was 0.68, and the interobserver ICC was 0.79. For tomosynthesis sagittal images, the intraobserver ICC was 0.85, and the interobserver ICC was 0.92. There was a strong positive correlation between the TS-VCA angle and the FP-VCA angle. When the FP-VCA angle was 25°, the TS-VCA angle was 35° in regression analysis. CONCLUSIONS: Measuring acetabular anterior coverage using sagittal plane tomosynthesis correlates well with FP radiography. Regardless of the presence of acetabular deformities, tomosynthesis demonstrated high reproducibility, simple posture setting, low effective doses, and high versatility. A cut-off value of 35° was useful for the detection of developmental dysplasia of the hip joint using the TS-VCA angle.

Axitinib-induced reversible posterior leukoencephalopathy syndrome in a patient with metastatic renal cell carcinoma.

A 61-year-old woman with metastatic renal carcinoma was treated with axitinib as a second-line tyrosine kinase inhibitor. Thirteen days after the treatment, the patient developed reversible posterior leukoencephalopathy syndrome (RPLS). Her symptoms and imaging findings resolved after withdrawal of axitinib, blood pressure control, and administration of glycerin and levetiracetam. RPLS should be kept in mind as a possible rare adverse event after axitinib administration.

Effects of a cell-free method using collagen vitrigel incorporating TGF-ß1 on articular cartilage repair in a rabbit osteochondral defect model.

We studied the ability of collagen vitrigel material to repair cartilage in vivo when used alone or with transforming growth factor-ß (TGF-ß). We measured the time course and quantity of TGF-ß1 released from the collagen vitrigel in vitro to quantify the controlled release of TGF-ß1. Over 14 days, 0.91 ng of TGF-ß was released from the collagen vitrigel. Osteochondral defects were made in the femoral trochlear groove in 36 Japanese white rabbits, which were divided into three groups: untreated group (group A), collagen vitrigel-implanted group (group B), and TGF-ß1-incorporated collagen vitrigel-implanted group (group C). The weight distribution ratio between the affected and unaffected limbs served as an indicator of pain. Animals were sacrificed at 4 and 12 weeks after surgery, and their tissues were assessed histologically. The weight distribution ratio increased in all groups and did not differ significantly between groups at 12 weeks. Group A needed 6 weeks to attain maximum improvement, and groups B and C showed near-maximum improvement at 4 and 2 weeks, respectively. The International Cartilage Repair Society II score improved significantly in group C relative to the other groups. These findings suggest that sustained, slow release of TGF-ß caused early pain mitigation and cartilage repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2592-2602, 2017.

Risk assessment and usefulness of musculocutaneous flap transposition for recurrent septic arthritis of the hip in adults.

PURPOSE: Septic arthritis of the hip joint in adults often progresses to recurrent infections that require repeated surgeries for treatment. The purpose of the present study was to assess the risk of a recalcitrant hip infection and the usefulness of musculocutaneous flap transposition. METHODS: 15 adult patients who underwent surgeries for the treatment of hip infections were retrospectively analysed. Patients who recovered from infection by undergoing arthroscopy, open irrigation, debridement, continuous irrigation, resection arthroplasty, and/or the placement of antibiotic-loaded acrylic cement were classified into Group A (n = 10). Patients who showed residual infection after multiple surgeries and ultimately recovered after undergoing musculocutaneous flap transposition were classified into Group B (n = 5). The age at onset, sex, incidence of multi-drug-resistant organisms, incidence of infection at other sites, compromising factors, peak preoperative C-reactive protein level, and period from onset to initial surgery were compared between groups. RESULTS: There was a statistically significant difference in the period from onset to initial surgery (p = 0.024). The infections remained chronic after multiple surgeries in most patients who had complications and/or a poor general or local condition. All of the patients recovered after musculocutaneous flap transposition without the need for additional surgery and did not experience recurrence during the follow-up period in Group B. CONCLUSIONS: Delayed diagnosis and/or treatment and compromised host caused recurrent septic arthritis of the hip in adults. Musculocutaneous flap transposition may be a useful method for the treatment of recalcitrant hip infection.

Spinal surgery following renal transplantation.

BACKGROUND: With the improvement in postoperative care for renal transplant patients, the number of patients requiring spinal surgery after renal transplantation has been increasing. However, there have been only a few reports describing the results of spinal surgery in renal transplant recipients. In this study, we investigated the results of spine surgery in renal transplant recipients. METHODS: A total of 37 renal transplant recipients who underwent spinal surgery in our hospital between April 2003 and July 2012 were included in this study. RESULTS: Perioperative complications were observed in 6 cases (16.2%). Two of them (5.3%) were general complications including duodenal ulcer and acute renal failure. The other four complications (10.8%) were directly related to surgery, namely, epidural hematoma, neurological deterioration and two surgical site infections. No patient required permanent hemodialysis postoperatively. Twenty-five fusion surgeries were performed and pseudoarthrosis was observed in 3 cases (12.0%). CONCLUSION: Spinal surgery in renal transplant recipients can be performed without major complications or requirement for permanent hemodialysis postoperatively. Our data also showed a high rate of surgical site infection and pseudoarthrosis after fusion surgery.

Optimal method for measuring tumor extent in needle biopsy specimens to identify small-volume prostate cancer.

OBJECTIVES: To compare various methods for measuring tumor extent in prostate biopsy specimens to identify small-volume prostate cancer. METHODS: A total of 100 radical prostatectomy specimens were retrospectively analyzed. Receiver operating characteristic analysis was used to compare the abilities of prostate-specific antigen density, and four measures of tumor extent in prostate biopsy specimens - positive core number, greatest percentage of cancer in a single core, greatest length of cancer in cores and total length of cancer in cores - to identify small volume prostate cancer. Four definitions of insignificant cancer volume were used in this analysis: index and total tumor volume <0.5 mL, index tumor volume <1.3 mL and total tumor volume <2.5 mL. Multivariate analysis was also used to evaluate variables for predicting small-volume prostate cancer. RESULTS: Total length of cancer in cores had the highest areas under the curve of all the measures defining small-volume prostate cancer: index tumor volume <0.5 mL (0.855), total tumor volume <0.5 mL (0.877), index tumor volume <1.3 mL (0.784) and total tumor volume <2.5 mL (0.818). On multivariate analysis total length of cancer in cores was an independent predictive factor for prostate cancers with index tumor volume <0.5 mL (P < 0.001), <1.3 mL (P < 0.001) and total tumor volume <0.5 mL (P < 0.001), respectively. CONCLUSION: Our data suggest that total length of cancer in cores is the optimal measure of tumor extent in prostate biopsy specimens for identifying small-volume prostate cancer.

Surgical Outcome for Hemodialysis-Related Upper Cervical Lesions.

STUDY DESIGN: A retrospective study. PURPOSE: To investigate the surgical outcome for hemodialysis-related upper cervical lesions. OVERVIEW OF LITERATURE: Surgical outcome of lower cervical lesions in patients undergoing hemodialysis has been reported. However, surgical outcome for upper cervical lesions in hemodialysis patients is unclear. METHODS: Upper cervical lesions in nine patients undergoing hemodialysis were surgically treated. Mean age at surgery was 61.6 years (range, 52-68 years), and the mean follow-up period was 45.4 months (range, 2-98 months). Patients had undergone hemodialysis for an average of 25.3 years (range, 16-40 years) at surgery. Seven patients with destructive spondyloarthropathy (DSA) of the upper cervical spine were treated with atlantoaxial or occipitocervical fixation. Two patients with retro-odontoid pseudotumors were treated with C1 posterior arch resection alone. Japanese Orthopedic Association (JOA) scores for cervical myelopathy, postoperative complications, postoperative radiography, and preoperative and postoperative occipital pain were evaluated. RESULTS: Mean preoperative and postoperative JOA score was 3.7 and 8.1, respectively. The seven patients with DSA had severe preoperative occipital pain that disappeared postoperatively. Postoperative radiography showed solid bone union in DSA cases and no instability in pseudotumor cases. CONCLUSIONS: Satisfactory surgical outcome was observed for hemodialysis-related upper cervical lesions.

L5 Radiculopathy due to Foraminal Stenosis Accompanied With Vacuum Phenomena of the L5/S Disc on Radiography Images in Extension Position.

STUDY DESIGN: Retrospective study for L5 radiculopathy due to foraminal stenosis with vacuum phenomena (VP) at the L5/S disc. OBJECTIVE: To investigate the influence of the L5/S VP on L5 radiculopathy, due to L5/S foraminal stenosis. SUMMARY OF BACKGROUND DATA: Foraminal stenosis has often been detected via images. However, although this condition is well known, it is occasionally overlooked during diagnosis, because spinal nerve compression is not always visible on stationary images. METHODS: Patients who underwent lumbar spine surgery were examined to determine the presence of foraminal stenosis (n = 194). The presence of VP and the range of motion of the L5/S disc were assessed on radiography with the lumbar spine in the extended and flexed positions. The shapes of the L5/S foramina were confirmed using sagittal magnetic resonance imaging. Patients who showed VP were divided into 2 groups: patients with (group A) and without (group B) symptomatic foraminal stenosis. The relationship between the VP and symptomatic foraminal stenosis was examined. RESULTS: In total, 35 cases of VP at the L5/S disc were noted on lateral radiography. L5 radiculopathy due to L5/S foraminal stenosis was identified in 14 of these 35 cases. The ranges of L5/S angles were 10°â€Š±â€Š4° and 5°â€Š±â€Š3° in groups A and B, respectively, and these values were significantly different (P < 0.01). 11 (48%) of 23 L5/S foramina that showed VP of the L5/S disc and were completely occupied by a disc below the caudal edge of the vertebra had symptomatic foraminal stenosis. CONCLUSION: Our results indicated that VP, which showed a large range of motion angle between flexion and extension, triggered symptoms of foraminal stenosis at the L5/S disc. The dynamic motion of the VP should thus be considered for the diagnosis of L5/S foraminal stenosis. LEVEL OF EVIDENCE: 3.

Penetration of piperacillin-tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics.

This study aimed to investigate the penetration of PIPC-TAZ into human prostate, and to assess effectiveness of PIPC-TAZ against prostatitis by evaluating site-specific PK-PD. Patients with prostatic hypertrophy (n = 47) prophylactically received a 0.5 h infusion of PIPC-TAZ (8:1.2-0.25 g or 4-0.5 g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T > MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC-TAZ regimens (2.25 or 4.5 g; once, twice, three times or four times daily; 0.5 h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (Cmax) and the area under the drug concentration-time curve (AUC). Against MIC distributions for isolates of Escherichia coli, Klebsiella species and Proteus species, regimens of 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% T > MIC) in prostate tissue. However, against Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability. PIPC-TAZ is appropriate for the treatment of prostatitis from the site-specific PK-PD perspective.

Differential diagnosis of tumoral lesions in the spinal canal in patients undergoing hemodialysis.

STUDY DESIGN: A retrospective study. PURPOSE: To clarify the features useful for the differential diagnosis of spinal canal tumoral lesions in patients undergoing hemodialysis. OVERVIEW OF LITERATURE: Tumoral lesions in the spinal canal are rarely found in hemodialysis patients. Therefore, the differential diagnosis of tumoral lesions in the spinal canal in hemodialysis patients has been very difficult. METHODS: Spinal canal tumors in 17 patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis were investigated. Histopathological analysis was conducted for all specimens obtained during surgery. The tumoral lesions were categorized into 3 groups on the basis of histopathology: spinal cord tumor, amyloidoma, and other. Patient medical history and diagnostic images of each group were reviewed. RESULTS: Eight of 17 cases were histopathologically diagnosed as spinal cord tumors and were neurinomas, 6 were amyloidomas, and 3 were classified as other. The rate of spinal cord tumors was 47.1% (8 of 17 cases), which revealed the most frequent lesion type. The rate of amyloidomas and other types was 35.3% (6 of 17 cases) and 17.6% (3 of 17cases), respectively. In the amyloidoma group, the mean duration of hemodialysis (24.3 years) was longer than that of spinal cord tumors and other types (9.2 years and 8.6 years, respectively). All spinal cord tumors were intradural extramedullary, whereas all amyloidomas and other types were extradural. CONCLUSIONS: The rate of each tumoral lesion, the duration of hemodialysis, and the tumoral localization are important features for the differential diagnosis of tumoral lesions in the spinal canal in hemodialysis patients.

Pycnodysostosis with Multi-Segmental Spinal Canal Stenosis due to Ossification of the Yellow Ligament.

Pycnodysostosis is an autosomal recessive disorder characterized by osteosclerosis, small stature, acro-osteolysis of the distal phalanges, loss of the mandibular angle, separated cranial sutures with open fontanels, and frequent fractures. One identified cause of the disease is reduced activity of the cysteine protease cathepsin K. A 48-year-old woman with a history of frequent fractures presented with a severe gait disturbance. Radiography, computed tomography, magnetic resonance imaging, and gene analysis were performed. Physical examination revealed open fontanels, and radiographs showed increased bone density. DNA sequence analysis revealed a deletion mutation of the cathepsin K gene. We diagnosed pycnodysostosis based on these findings. The magnetic resonance and computed tomography images demonstrated multilevel spinal canal stenosis due to ossification of the yellow ligament. We performed a laminectomy, and the patient's neurological signs and symptoms improved. To our knowledge, this is the first case of pycnodysostosis with ossification of the yellow ligament.